Ont Health Technol Assess Ser. 2017; 17(15): 1–167. Published online 2017 Nov 13. Major depressive disorder and generalized anxiety disorder are among the most commonly diagnosed mental illnesses in Canada; both are associated with a high
societal and economic burden. Treatment for major depressive disorder and generalized anxiety disorder consists of pharmacological and psychological interventions. Three commonly used psychological interventions are cognitive behavioural therapy (CBT), interpersonal therapy, and supportive therapy. The objectives of this report were to assess the effectiveness and safety of these types of therapy for the treatment of adults with major depressive disorder and/or generalized anxiety disorder, to
assess the cost-effectiveness of structured psychotherapy (CBT or interpersonal therapy), to calculate the budget impact of publicly funding structured psychotherapy, and to gain a greater understanding of the experiences of people with major depressive disorder and/or generalized anxiety disorder. We performed a literature search on October 27, 2016, for systematic reviews that compared CBT, interpersonal therapy, or supportive
therapy with usual care, waitlist control, or pharmacotherapy in adult outpatients with major depressive disorder and/or generalized anxiety disorder. We developed an individual-level state-transition probabilistic model for a cohort of adult outpatients aged 18 to 75 years with a primary diagnosis of major depressive disorder to determine the cost-effectiveness of individual or group CBT (as a representative form of structured psychotherapy) versus usual care. We also estimated the 5-year
budget impact of publicly funding structured psychotherapy in Ontario. Finally, we interviewed people with major depressive disorder and/or generalized anxiety disorder to better understand the impact of their condition on their daily lives and their experience with different treatment options, including psychotherapy. Interpersonal therapy compared with usual care reduced posttreatment major depressive disorder scores
(standardized mean difference [SMD]: 0.24, 95% confidence interval [CI]: −0.47 to −0.02) and reduced relapse/recurrence in patients with major depressive disorder (relative risk [RR]: 0.41, 95% CI: 0.27–0.63). Supportive therapy compared with usual care improved major depressive disorder scores (SMD: 0.58, 95% CI: 0.45–0.72) and increased posttreatment recovery (odds ratio [OR]: 2.71, 95% CI: 1.19–6.16) in patients with major depressive disorder. CBT compared with usual care increased response
(OR: 1.58, 95% CI: 1.11–2.26) and recovery (OR: 3.42, 95% CI: 1.98–5.93) in patients with major depressive disorder and decreased relapse/recurrence (RR: 0.68, 95% CI: 0.65–0.87]). For patients with generalized anxiety disorder, CBT improved symptoms posttreatment (SMD: 0.80, 95% CI: 0.67–0.93), improved clinical response posttreatment (RR: 0.64, 95% CI: 0.55–0.74), and improved quality-of-life scores (SMD: 0.44, 95% CI: 0.06–0.82). There was a significant difference in posttreatment recovery
(OR: 1.98, 95% CI: 1.11–3.54) and mean major depressive disorder symptom scores (weighted mean difference: −3.07, 95% CI: −4.69 to −1.45) for patients who received individual versus group CBT. Details about the providers of psychotherapy were rarely reported in the systematic reviews we examined. In the base case probabilistic cost–utility analysis, compared with usual care, both group and individual CBT were associated with increased survival: 0.11 quality-adjusted life-years
(QALYs) (95% credible interval [CrI]: 0.03–0.22) and 0.12 QALYs (95% CrI: 0.03–0.25), respectively. Group CBT provided by nonphysicians was associated with the smallest increase in discounted costs: $401 (95% CrI: $1,177 to 1,665). Group CBT provided by physicians, individual CBT provided by nonphysicians, and individual CBT provided by physicians were associated with the incremental costs of $1,805 (95% CrI: 65–3,516), $3,168 (95% CrI: 889–5,624), and $5,311 (95% CrI:
2,539–8,938), respectively. The corresponding incremental cost-effectiveness ratio (ICER) was lowest for group CBT provided by nonphysicians ($3,715/QALY gained) and highest for individual CBT provided by physicians ($43,443/QALY gained). In the analysis that ranked best strategies, individual CBT versus group CBT provided by nonphysicians yielded an ICER of $192,618 per QALY. The probability of group CBT provided by nonphysicians being cost-effective versus usual care was greater than 95% for
all willingness-to-pay thresholds over $20,000 per QALY and was around 88% for individual CBT provided by physicians at a threshold of $100,000 per QALY. We estimated that adding structured psychotherapy to usual care over the next 5 years would result in a net budget impact of $68 million to $529 million, depending on a range of factors. We also estimated that to provide structured psychotherapy to all adults with major depressive disorder (alone or combined with generalized
anxiety disorder) in Ontario by 2021, an estimated 500 therapists would be needed to provide group therapy, and 2,934 therapists would be needed to provide individual therapy. People with major depressive disorder and/or generalized anxiety disorder with whom we spoke reported finding psychotherapy effective, but they also reported experiencing a large number of barriers that prevented them from finding effective psychotherapy in a timely manner. Participants reported wanting
more freedom to choose the type of psychotherapy they received. Compared with usual care, treatment with CBT, interpersonal therapy, or supportive therapy significantly reduces depression symptoms posttreatment. CBT significantly reduces anxiety symptoms posttreatment in patients with generalized anxiety disorder. Compared with usual care, treatment with structured psychotherapy (CBT or interpersonal therapy)
represents good value for money for adults with major depressive disorder and/or generalized anxiety disorder. The most affordable option is group structured psychotherapy provided by nonphysicians, with the selective use of individual structured psychotherapy provided by nonphysicians or physicians for those who would benefit most from it (i.e., patients who are not engaging well with or adhering to group therapy). This health technology assessment looked at the effectiveness, safety, cost-effectiveness, budget impact, and patient experiences of cognitive behavioural therapy (CBT), interpersonal therapy, and supportive therapy for the treatment of major depressive disorder and generalized anxiety disorder to determine whether these therapies should be publicly funded. Major
depressive disorder is the second largest health care problem worldwide in terms of illness-induced disability.1 The essential feature of major depressive disorder is the occurrence of one or more major depressive episodes. Major depressive episodes are defined as periods lasting at least 2 weeks characterized by depressed mood, most of the day, nearly every day, and/or
markedly diminished interest or pleasure in all, or almost all, activities.2 To receive a diagnosis of major depressive disorder, within the same 2-week period a person must experience 5 or more symptoms from the criteria for a major depressive episode as described in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5).3 Generalized anxiety disorder is a chronic (constantly recurring) anxiety disorder characterized by persistent, excessive, and difficult-to-control worry that may be accompanied by several psychic (mental) symptoms and somatic (bodily) symptoms.4 It is
associated with high rates of comorbidity (having more than one condition at a time), and 68% of people with generalized anxiety disorder report having at least one other psychiatric illness (usually depression, another anxiety disorder, or a substance use disorder).4 The current classification of depressive and anxiety disorders is based on the DSM-5 or the tenth revision
of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) Classification of Mental and Behavioural Disorders.5 The lifetime prevalence of major depressive disorder in Canada is 10.8%; annual and 1-month prevalence estimates are 4.0% and 1.3%,
respectively.2 Depression affects occupational functioning both through absenteeism and through loss of productivity while attending work when unwell.2 While occupational impairment receives much attention, depression also negatively affect
people's ability to perform personal activities, such as parenting and housekeeping. A study in the United States found that people with major depressive disorder were able to perform better at work than in their personal activities.6 Treatment for acute major depressive disorder (during the first 3 months after diagnosis) often consists of
pharmacological interventions (medications including selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, and tricyclic antidepressants) and psychological interventions (talk therapies). The prescribing of antidepressant medications has increased over the last 20 years, mainly owing to the development of a new type of antidepressant medication called selective serotonin reuptake inhibitors, as well as other newer
agents.7 While antidepressants continue to be the mainstay of treatment for major depressive disorder, adherence rates remain low in part because of patients' concerns about side effects and possible dependency. In addition, surveys have demonstrated patients' preference for psychological interventions over treatment with
antidepressants.7 Therefore, psychological therapies can provide an alternative or additional intervention for major depressive disorder.7 Major depressive disorder is both chronic (lasting 3 months or more) and episodic
(consisting of separate episodes) in nature. It consists of initial phases (i.e., the acute and continuation phases, each lasting approximately 3 months) and a maintenance phase (lasting approximately 6 to 24 months, with an average 9 to 12
months).2,8–10 The aim of treatment in the acute and continuation phases is the remission (reduction or elimination) of symptoms and the
restoration of psychosocial functioning (a return to the level of psychological and social functioning experienced before the onset of major depressive disorder).2 The aim of treatment in the maintenance phase is to prevent symptoms from
recurring.2 In Canada, the 1-year prevalence of generalized anxiety disorder in the general population is about 1% to 3%, and the lifetime prevalence is about 6%.4 Patients with generalized anxiety disorder may experience multiple episodes of the
disease over their lifetime, and these episodes may be associated with a multitude of disabilities affecting work, education, and social interactions.4 The primary treatment for generalized anxiety disorder consists of medications (e.g., selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, anxiolytics, and other
agents).4 Antidepressants are the first-line treatment (the first type of treatment tried) and have the additional benefit of treating ruminative worry (persistent negative thoughts) and any coexisting depressive symptoms.4 Benzodiazepines, which have a sedative and anti-anxiety
effect, were used extensively in the past; however, owing to the potential for developing tolerance and dependence with prolonged use, most guidelines now recommend that for generalized anxiety disorder, benzodiazepines be prescribed for no longer than 2 to 4 weeks.4 As a result of patients' concerns about side effects, psychotherapy is a treatment option that may be
considered either as an alternative or additional intervention for generalized anxiety disorder.11 Three common types of psychotherapy for the treatment of major depressive disorder and generalized anxiety disorder are cognitive behavioural therapy (CBT), interpersonal
therapy, and supportive therapy.12 The Royal Australian and New Zealand College of Psychiatrists defines structured psychotherapy as “the treatment of mental or emotional illness by using defined (often manualized) psychological techniques, pre-planned with clear goals and employed within a specific
timeframe.”13 According to the College, patients must be seen by their treatment provider, either individually or in a small group, on at least a monthly basis.13 CBT and interpersonal therapy are considered structured psychotherapies, but supportive therapy is
not.13 Cognitive behavioural therapy focuses on helping patients become aware of how certain negative automatic thoughts, attitudes, expectations, and beliefs contribute to feelings of sadness and anxiety.12 Patients learn how these thinking patterns, which may
have developed in the past to deal with difficult or painful experiences, can be identified and changed to reduce unhappiness.12 Interpersonal therapy focuses on identifying and resolving problems in establishing and maintaining satisfying relationships.12 Such
problems may include dealing with loss, life changes, conflicts, and increasing ease in social situations.12 Supportive therapy (also called nondirective supportive therapy) is typically an unstructured therapy that relies on the basic interpersonal skills of the therapist, such as reflection, empathic listening, and encouragement. It has been defined as a psychological
treatment in which therapists do not engage in any therapeutic strategy other than active listening and offering support, focusing on patients' problems and concerns.14 It focuses more on current problems rather than long-term difficulties.12 The overall goal
is to reduce patients' discomfort level and help them cope with their current circumstances.12,14 In Ontario, the delivery of psychotherapy from a psychiatrist or other physician trained in
psychotherapy is publicly funded. Services provided by other regulated (i.e., registered), trained health care professionals (e.g., nurses, occupational therapists, psychologists, psychotherapists, and social workers) may be free to patients if the services are offered in government-funded hospitals, clinics, or agencies.12 However, many free services have long wait lists. Other free
services include employee assistance programs, community clinics, support groups, distress lines, and drop-in centres. Therapy provided by registered psychologists or psychotherapists in private practice is not publicly funded. However, the fees may be covered by private insurance or workplace coverage, although such private or workplace plans may not cover the full amount or may provide coverage for only certain types of
therapist.12 In the United States, the Medicare program covers outpatient mental health services and visits with the following professionals15: Psychiatrist or other physician Clinical psychologist Clinical social worker Clinical nurse specialist Nurse practitioner Physician assistant Medicare covers counselling or therapy only when delivered by a health care professional who accepts assignment, which is an agreement by a health care professional to (a) be paid directly by Medicare; (b) accept the payment amount that Medicare approves for the service; and (c) not bill
the patient for more than the fee of the Medicare deductible and coinsurance.15 There are caveats around the specific amount a patient is required to pay for treatment depending on several factors, such as the following15: Other insurance the patient
may have How much the health care professional charges Whether the provider accepts assignment The type of facility in which treatment is provided The location where the patient receives treatment Health care professionals may recommend a patient receive treatment more often than what Medicare will
cover.15 Or, they may recommend services that Medicare does not cover. In such cases, the patient may have to pay some or all of the treatment costs.15 What are the effectiveness and safety of cognitive behavioural therapy (CBT), interpersonal therapy, and supportive therapy in improving outcomes for adult patients with major depressive disorder and adult patients with generalized anxiety disorder? What are the effectiveness and safety of individual versus group therapy? What are the effectiveness and safety of psychotherapy versus no treatment or waitlist control? What are the
effectiveness and safety of psychotherapy with and without pharmacotherapy versus pharmacotherapy only? What are the effectiveness and safety of psychotherapy provided by physician versus nonphysician providers? MethodsResearch questions are developed by Health Quality Ontario in consultation with experts, end users, and/or applicants in the topic area. Our methodological approaches align with Health Quality Ontario's Health Technology Assessments Methods and Process Guide.16 Literature SearchWe performed a literature search on October 27, 2016, to retrieve studies published from January 1, 2000, until the search date. We used the Ovid interface to search the following databases: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Embase, Health Technology Assessment, MEDLINE, National Health Service Economic Evaluation Database (NHSEED), and PsycINFO. We used the EBSCOhost interface to search the Cumulative Index to Nursing & Allied Health Literature (CINAHL). Search strategies were developed by medical librarians using controlled vocabulary (e.g., Medical Subject Headings) and relevant keywords. Methodological filters were used to limit retrieval to systematic reviews, meta-analyses, and health technology assessments. The final search strategy was peer-reviewed using the Peer Review of Electronic Search Strategies (PRESS) checklist.17 Database auto-alerts were created in CINAHL, Embase, MEDLINE, and PsycINFO and monitored for the duration of the health technology assessment review. We performed targeted grey literature searching of health technology assessment agency websites and PROSPERO systematic review registry. See Appendix 1 for the literature search strategies, including all search terms. Literature ScreeningA single reviewer reviewed the abstracts, and, for those studies meeting the eligibility criteria, we obtained full-text articles. We also examined reference lists for any additional relevant studies not identified through the search. Inclusion Criteria
Exclusion Criteria
Outcomes of Interest
Data ExtractionWe extracted relevant data on study characteristics; risk-of-bias items; and population, intervention, comparison, outcome, and time (PICOT) criteria using a standardized data form. The form collected information about the following:
Statistical AnalysisThis review reports results only from systematic reviews. We did not perform an analysis of primary studies. Quality of EvidenceWe used A Measurement Tool to Assess Systematic Reviews (AMSTAR) to assess the methodological quality of systematic reviews.18 See Appendix 2 for details of the AMSTAR analysis. Expert ConsultationIn December 2016, we sought expert consultation on the use of CBT, interpersonal therapy, and supportive therapy for the treatment of major depressive disorder and generalized anxiety disorder. Members of the consultation included health care professionals in the specialty areas of psychology, psychiatry, and family medicine. The role of the expert advisors was to help contextualize the evidence and provide advice on the use of CBT, interpersonal therapy, and supportive therapy for the treatment of major depressive disorder and generalized anxiety disorder. However, the statements, conclusions, and views expressed in this report do not necessarily represent the views of the consulted experts. ResultsLiterature SearchThe database and grey literature searches yielded 1,759 citations published between January 1, 2000, and October 27, 2016 (after duplicates removed). We reviewed titles and abstracts to identify potentially relevant articles and obtained the full texts of these articles for further assessment. Thirteen systematic reviews met the inclusion criteria. We hand-searched the reference lists of the included studies, and other sources, to identify any additional relevant studies. Figure 1 presents the flow diagram for the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) for the clinical evidence review. PRISMA Flow Diagram—Clinical Evidence Review Abbreviations: GAD, generalized anxiety disorder; MDD, major depressive disorder; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses. Source: Adapted from Moher et al.19 Cognitive Behavioural Therapy Compared With Usual Care for Major Depressive DisorderDepressive Symptoms, Treatment Response, and RemissionThree systematic reviews reported results for symptoms of major depressive disorder after patients received CBT compared with usual care.20–22 In 2016, Cuijpers et al systematically reviewed the effectiveness of CBT for the acute treatment of major depressive disorder compared with control (wait list, usual care, or pill placebo) (63 randomized controlled trials, number of patients not reported).20 Overall, CBT significantly reduced mean major depressive disorder symptom scores for patients who had undergone CBT compared with control (SMD: 0.75, 95% CI: 0.64–0.87]).20 Cuijpers et al reported that 11 of the 63 studies were rated high quality, based on the Cochrane risk-of-bias tool.20 Of note, the authors analyzed for publication bias and estimated that approximately 14% of major depressive disorder studies were missing from publication; thus, the pooled effect size dropped from an SMD of 0.75 to an SMD of 0.65 (95% CI: 0.53–0.78).20 No studies reviewed by Cuijpers et al reported on the providers of CBT.20 Linde et al conducted a meta-analysis to determine the effectiveness of psychotherapy compared with usual care or placebo in primary care patients with major depressive disorder.21 The authors conducted an analysis of 7 randomized controlled trials (N = 518) for face-to-face CBT. The meta-analysis included 5 studies23–27 that were also included in the systematic review by Cuijpers et al.20 The standardized mean difference for posttreatment major depressive disorder symptom scores compared with control was statistically significant, favouring CBT: −0.30 (95% CI: −0.48 to −0.13). Linde et al also reported a statistically significant pooled estimate for response (defined as a ≥ 50% score reduction on a depression scale) favouring CBT and a statistically nonsignificant pooled estimate for remission (defined as a symptom score below a fixed threshold) for CBT compared with usual care (OR: 1.58, 95% CI: 1.11–2.26, and OR: 1.49, 95% CI: 0.90–2.46, respectively).21 The authors rated the overall quality of the trials in the systematic review as low, based on the Cochrane risk-of-bias criteria.21 The reporting of intervention details for usual care and for co-interventions (e.g., pharmacotherapy) in the groups receiving psychotherapy was often insufficient.21 The providers of treatment in the included studies varied and included counsellors, nurses, psychiatrists, psychologists, psychotherapists, and therapists.21 Churchill et al22 systematically reviewed psychotherapies for the treatment of major depressive disorder and performed an analysis for CBT compared with usual care. Of the 20 studies included in the analysis, 424,25,27,28 were also included in the more recent systematic review by Cuijpers et al.20 Overall, there was a significant difference in posttreatment recovery (12 studies, N = 654; OR: 3.42, 95% CI: 1.98–5.93).22 Posttreatment recovery was defined as patients no longer being deemed to have a clinically meaningful level of depression, as indicated by a score of less than 10 on the Beck Depression Inventory or less than 6 on the Hamilton Depression Rating Scale. The authors also found a significant difference in mean major depressive disorder symptom scores for patients who received CBT versus usual care (20 studies, N = 748; SMD: −1.0, 95% CI: −1.35 to −0.64).22 Churchill et al also reported results for individual versus group CBT.22 Overall, there was a significant difference in posttreatment recovery (6 studies, N = 234; OR: 1.98, 95% CI: 1.11–3.54) and mean major depressive disorder symptom scores (8 studies, N = 283; weighted mean difference [WMD]: −3.07, 95% CI: −4.69 to −1.45]) for patients who received individual versus group CBT.22 The authors rated the overall quality of evidence as low, based on the Cochrane risk-of-bias tool, owing to low scores on internal validity and inadequate reporting of methodology.22 No studies reviewed by Churchill et al reported on the providers of CBT.22 RelapseThree systematic reviews reported results for relapse of major depressive disorder after patients had received treatment with CBT versus usual care.29–31 Biescheuvel-Leliefeld et al systematically reviewed the effectiveness of psychological interventions compared with usual care or antidepressant drugs in reducing relapse or recurrence rates of patients in remission.29 Usual care was defined as routine clinical management, assessment only, no treatment, or wait list. Relapse and recurrence were defined by the primary study investigators; examples include surpassing a threshold score on a depression scale and demonstrating a change in diagnostic depression status based on clinical assessment. The authors also conducted a subset analysis of 16 randomized controlled trials (N = 529) for CBT.29 CBT significantly reduced the risk of relapse or recurrence compared with usual care (RR: 0.68, 95% CI: 0.65–0.87) but not compared with antidepressant drugs (RR: 0.79, 95% CI: 0.61–1.02).29 The authors rated the overall quality of evidence as low, according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria, owing to varying definitions of remission, recovery, relapse, and recurrence in the primary studies.29 No studies reviewed by Biescheuvel-Leliefeld et al reported on the providers of CBT.29 Clarke et al conducted a meta-analysis to determine the effectiveness of nonpharmacological interventions compared with control (defined as usual care, clinical management, or antidepressant drugs) in people who had recovered from major depressive disorder (defined as being in full or partial remission).30 The authors also conducted a subset analysis of nine randomized controlled trials (N = 853) for CBT. The systematic review included three randomized controlled trials32–34 also included in the meta-analysis by Biescheuvel-Leliefeld et al.29 At 12 and 24 months, the risk of developing a new episode of major depressive disorder was significantly reduced in patients who had received CBT compared with control (RR: 0.75, 95% CI: 0.64–0.89, and RR: 0.72, 95% CI: 0.57–0.91, respectively.30 The authors rated the overall quality of evidence as low, based on the GRADE criteria.30 No studies reviewed by Clarke et al reported on the providers of CBT.30 Guidi et al31 systematically reviewed the effectiveness of CBT compared with usual care or clinical management in the treatment of people with major depressive disorder who had successfully responded to a previous course of treatment with antidepressant drugs. (The difference between usual care and clinical management was not described.) Effectiveness was assessed in terms of relapse or recurrence rates of major depressive disorder. All 13 studies (N = 1,410) reviewed by Guidi et al31 were also included in the reviews by Biescheuvel-Leliefeld et al29 and/or Clarke et al.30 The overall pooled risk ratio for relapse or recurrence for CBT compared with usual care or clinical management was statistically significant, favouring CBT (0.78; 95% CI: 0.67–0.91). The authors reported that the methodological quality of the studies included in their meta-analysis was high; however, they did not report their method of rating study quality.31 No studies reviewed by Guidi et al reported on the providers of CBT.31 Adverse EventsThis outcome was not reported in the systematic reviews. Quality of LifeThis outcome was not reported in the systematic reviews. Cognitive Behavioural Therapy With and Without Pharmacotherapy Compared With Pharmacotherapy Only for Major Depressive DisorderDepressive Symptoms, Treatment Response, and RemissionThree systematic reviews reported results for treatment response after patients received CBT and pharmacotherapy compared with pharmacotherapy only for the treatment of major depressive disorder.35–37 Karyotaki et al systematically reviewed the effectiveness (as measured by response rate) of combined pharmacotherapy and psychotherapy compared with psychotherapy only or pharmacotherapy only in both the acute and maintenance treatment of patients with major depressive disorder. The authors also conducted a subset analysis for CBT.35 For acute-phase treatment, there was no significant difference in response rate for combined CBT and pharmacotherapy compared with CBT only at up to 6 months postrandomization (5 comparisons, number of patients not reported; OR: 1.51, 95% CI: 0.79–2.86) and up to 1 year postrandomization (4 comparisons, number of patients not reported; OR: 1.48, 95% CI: 0.59–3.71).35 However, there was a significant difference in response rate when the combination of CBT and pharmacotherapy was compared with pharmacotherapy only at up to 6 months (6 comparisons, number of patients not reported; OR: 3.02, 95% CI: 1.74–5.25) and up to 1 year postrandomization (4 comparisons, number of patients not reported; OR: 3.37, 95% CI: 1.38–8.21).35 For maintenance-phase treatment, no data were available for combined CBT and pharmacotherapy versus CBT only.35 There was a significant difference in response rate when the combination of CBT and pharmacotherapy was compared with pharmacotherapy only at up to 6 months postrandomization (4 comparisons, number of patients not reported; OR: 1.79, 95% CI: 1.19–2.70).35 No data were available for response rates at more than 1 year postrandomization.35 The authors rated the overall quality of evidence as low, based on the Cochrane risk-of-bias tool.35 No studies reviewed by Karyotaki et al reported on the providers of CBT.35 Amick et al meta-analyzed studies to determine the effectiveness (as measured by the rate of response and remission) of second-generation antidepressants (the most commonly prescribed class of antidepressants, including selective serotonin reuptake inhibitors and serotonin– norepinephrine reuptake inhibitors) only versus CBT only and second-generation antidepressants only versus a combination of second-generation antidepressants and CBT for the treatment of major depressive disorder.36 Response was defined as a decrease in depressive severity of equal to or greater than 50%, and remission was defined by the authors of the individual trials.36 For second-generation antidepressants only compared with CBT only, there were no significant differences in remission (3 trials; risk ratio: 0.98, 95% CI: 0.73–1.32), response (5 trials; risk ratio: 0.91, 95% CI: 0.77–1.07), or overall treatment discontinuation (4 trials; risk ratio: 1.00, 95% CI: 0.55–1.81).36 For second-generation antidepressants only compared with a combination of second-generation antidepressants and CBT, the authors found no significant differences for remission (1 trial; risk ratio: 1.06, 95% CI: 0.82–1.38); response (1 trial; risk ratio: 1.03, 95% CI: 0.85–1.26); or overall treatment discontinuation (1 trial; risk ratio: 0.77, 95% CI: 0.37–1.60).36 The authors rated the overall strength of evidence as low, based on methods guidance from the Evidence-Based Practice Centers Program of the Agency for Healthcare Research and Quality.36 The treatment providers in the studies reviewed by Amick et al varied in terms of provider type, training, and experience.36 Cuijpers et al systematically reviewed the effectiveness of acute-phase CBT without any subsequent continuation treatment compared with pharmacotherapy (that was either continued or discontinued) in patients with major depressive disorder.37 The primary outcome was the number of patients who responded to treatment and remained well (defined as treatment response maintained across 6 to 18 months of follow-up).37 Overall, the authors identified 9 studies (N = 506; for CBT, n = 271; for pharmacotherapy, n = 235).37 For acute-phase CBT (without continuation treatment) compared with acute-phase pharmacotherapy with continued pharmacotherapy during follow-up, there was no significant difference in 1-year outcomes (5 studies; OR: 1.62, 95% CI: 0.97–2.72).37 For acute-phase CBT (without continuation treatment) compared with acute-phase pharmacotherapy that was discontinued during follow-up, there was a significant difference in 1-year outcomes, favouring CBT (8 studies; OR: 2.61, 95% CI: 1.58–4.31).37 The authors rated the overall quality of evidence as high, according to the Cochrane risk-of-bias tool.37 No studies reviewed by Cuijpers et al reported on the providers of CBT.37 RelapseThis outcome was not reported in the systematic reviews. Adverse EventsThis outcome was not reported in the systematic reviews. Quality of LifeThis outcome was not reported in the systematic reviews. Cognitive Behavioural Therapy Compared With Usual Care for Generalized Anxiety DisorderAnxiety Symptoms, Treatment Response, and RemissionThree systematic reviews reported results for treatment response after patients received CBT compared with usual care for the treatment of generalized anxiety disorder.11,20,38 In 2016, Cuijpers et al systematically reviewed the effectiveness of CBT (as measured by reduction in anxiety symptoms) compared with control (wait list, usual care, or pill placebo) for the acute treatment of patients with anxiety disorders.20 A subset analysis was conducted for generalized anxiety disorder (31 studies, number of patients not reported). Overall, mean generalized anxiety disorder symptom scores were significantly reduced by CBT compared with control (SMD: 0.80, 95% CI: 0.67–0.93).20 The authors rated 9 of the 31 studies as high quality, based on the Cochrane risk-of-bias tool.20 Of note, the authors analyzed for publication bias, and they estimated that about one-quarter of generalized anxiety disorder studies were missing. After adjusting for these missing studies, the effect size dropped from an SMD of 0.80 to an SMD of 0.59 (95% CI: 0.44–0.75). However, this result did not change the statistical significance of the finding.20 No studies reviewed by Cuijpers et al reported on the providers of CBT.20 In 2014, Cuijpers et al meta-analyzed studies to determine the effectiveness of psychotherapies versus control (wait list, usual care, or pill placebo) for people with generalized anxiety disorder.38 The authors also conducted a subset analysis for CBT (28 comparisons, number of patients not reported). We determined that there was overlap between the studies included in this 2014 analysis and those included in the systematic review by Cuijpers et al in 2016 (described above)20; however, the studies within the CBT subset comparison reported in the 2016 systematic review were unique to that publication.38 Overall, there was no significant difference in mean generalized anxiety disorder symptom scores posttreatment for people treated with CBT compared with control (SMD: 0.90, 95% CI: 0.75–1.05).38 The authors rated the overall quality of the studies included in the 2014 systematic review as low, based on the Cochrane risk-of-bias tool.38 The authors commented that the overall quality of the interventions also varied across studies (e.g., not all psychotherapy providers reported using a standard manual, and limited information was provided on treatment components, including those of CBT, and adherence to treatment manuals).38 The authors further stated that the literature on psychotherapy studies for generalized anxiety disorder differs markedly from that for major depressive disorder, in which the same standard treatment manual is used across many studies.38 The authors did not report publication bias for the subset analysis. No studies reviewed by Cuijpers et al reported on the providers of CBT.38 In 2007, Hunot et al systematically reviewed the effectiveness of CBT compared with usual care or wait list for the treatment of patients with generalized anxiety disorder.11 Primary outcomes included clinical response (8 studies, N = 334) and reduction in generalized anxiety disorder symptoms (12 studies, N = 350) posttreatment.11 There was a significant difference in clinical response and reduction in generalized anxiety disorder symptoms, favouring CBT versus usual care or wait list (RR: 0.64, 95% CI: 0.55–0.74, and SMD: −1.00, 95% CI: −1.24 to −0.77], respectively).11 Seven39–45 of the 12 studies included in the outcome of reduction in generalized anxiety disorder symptom response were also included in the meta-analysis by Cuijpers et al.20 The authors also conducted subset analyses for individual CBT (9 studies) and for group CBT (4 studies) compared with usual care or wait list.11 Patients in individual or group CBT achieved clinical response significantly more than patients in usual care or on wait list (RR: 0.63, 95% CI: 0.51–0.76, and RR: 0.66, 95% CI: 0.54–0.82, respectively).11 Similarly, there was a significant difference in generalized anxiety disorder symptoms, favouring CBT (individual CBT: SMD: −0.98, 95% CI: −1.32 to −0.65; group CBT: SMD: −1.02, 95% CI: −1.35 to −0.69]).11 Hunot et al reported an overall moderate risk of bias for the included studies, according to criteria set out in the Cochrane Handbook.11 The authors reported that the providers of treatment in the studies varied and were described as clinical psychologists; doctoral-, senior-, or advanced-level CBT therapists; “experienced therapists”; or “therapists.”11 RelapseThis outcome was not reported in the systematic reviews. Adverse EventsThis outcome was not reported in the systematic reviews. Quality of LifeHunot et al reported on posttreatment improvement in quality of life (3 studies, N = 112).11 The difference in quality-of-life mean scores between people who received CBT and those in the treatment-as-usual/waitlist group was significant, in favour of CBT (SMD: 0.44, 95% CI: 0.06–0.82).11 Interpersonal Therapy Compared With Usual Care for Major Depressive DisorderDepressive Symptoms, Treatment Response, and RemissionTwo systematic reviews reported results for a reduction in depressive symptoms after treatment with interpersonal therapy versus usual care.21,46 Jakobsen et al46 conducted a meta-analysis of 4 randomized controlled trials (N = 553) and reported a significant reduction in depression symptoms for patients with acute major depressive disorder treated with interpersonal therapy compared with usual care. This reduction was based on scores on the Hamilton Depression Rating Scale and the Beck Depression Inventory (mean differences: −3.53 [95% CI: −4.91 to −2.16, P < .0001] and −3.09 [95% CI: −5.35 to −0.83, P = .007]). The authors also reported a significant reduction in the number of patients who did not experience remission (defined as a Hamilton Depression Rating Scale score < 8) in the interpersonal therapy versus treatment-as-usual group (OR: 0.36, 95% CI: 0.24–0.55).46 The authors reported that all trials in the systematic review had a high risk of bias, based on the Cochrane risk-of-bias criteria.46 No studies reviewed by Jakobsen et al reported on the providers of interpersonal therapy, and the definition of usual care varied across the studies (e.g., standard care, clinical management).46 Linde et al conducted a meta-analysis to determine the effectiveness of psychotherapy versus usual care or placebo in primary care patients with major depressive disorder.21 The authors also conducted a meta-analysis of 2 randomized controlled trials (N = 305) for interpersonal therapy. One randomized controlled trial47 was also included in the meta-analysis by Jakobsen et al.46 The standardized mean difference for the posttreatment major depressive disorder scores of patients who had undergone interpersonal therapy compared with control was −0.24 (95% CI: −0.47 to −0.02),21 which indicates that interpersonal therapy significantly improved depression symptoms compared with control. The authors also reported pooled estimates for response (defined as a depression scale score reduction of ≥ 50%) and remission (defined as a symptom score below a fixed threshold) (OR: 1.28 [95% CI: 0.80–2.05] and OR: 1.37 [95% CI: 0.81–2.34], respectively).21 These results indicate that there was no significant difference between interpersonal therapy and usual care in terms of response or remission. The authors rated the overall quality of evidence as low, based on the Cochrane risk-of-bias criteria.21 The providers of treatment in the studies reviewed by Linde et al varied and included counsellors, nurses, psychiatrists, psychologists, psychotherapists, and therapists.21 (No distinction between “psychotherapist” and “therapist” was made.) The reporting of intervention details for usual care and co-interventions (e.g., pharmacotherapy) in the groups receiving psychological treatment was often insufficient.21 In 2001, Churchill et al22 conducted a systematic review of psychological treatments compared with usual care for the treatment of major depressive disorder. The authors also conducted a subset analysis of 1 randomized controlled trial47 (N = 185) for interpersonal therapy. Since this single trial was also included in the meta-analyses of Linde et al,21 Biesheuvel-Leliefeld et al,29 and Jakobsen et al,46 details of this study are not discussed here. RelapseTwo systematic reviews reported results for relapse of major depressive disorder after patients received treatment with interpersonal therapy versus usual care.29,30 Biescheuvel-Leliefeld et al systematically reviewed the effectiveness of psychological interventions compared with usual care or antidepressant drugs in reducing relapse or recurrence rates of patients in remission.29 Usual care was defined as routine clinical management, assessment only, no treatment, or wait list. Relapse and recurrence were defined by the primary study investigators; examples include surpassing a threshold score on a depression scale and demonstrating a change in diagnostic depression status based on clinical assessment. The authors also conducted a subset analysis of 3 randomized controlled trials (N = 142) for interpersonal therapy. The systematic review included 1 randomized controlled trial47 also included in the meta-analyses by Jakobsen et al46 and Linde et al.21 Interpersonal therapy significantly reduced the risk of relapse or recurrence compared with usual care (RR: 0.41, 95% CI: 0.27–0.63) but not compared with antidepressant drugs (RR: 0.83, 95% CI: 0.50–1.38).29 The authors rated the overall quality of evidence for relapse as low, according to the GRADE criteria, owing to varying definitions of remission, recovery, relapse, and recurrence in the primary studies.29 No studies reviewed by Biescheuvel-Leliefeld et al reported on the providers of interpersonal therapy.29 Clarke et al conducted a meta-analysis of 3 randomized controlled trials (N = 342) for interpersonal therapy to determine its effectiveness compared with control (defined as usual care, clinical management, or antidepressant drugs) in patients who had recovered from major depressive disorder (defined as being in full or partial remission).30 One randomized controlled trial48 was included in the meta-analysis by Biescheuvel-Leliefeld et al.29 At 12 months, the risk of developing a new episode of major depressive disorder was significantly reduced in patients who had received interpersonal therapy compared with control (RR: 0.78, 95% CI: 0.65–0.95).30 At 24 months, there was no significant difference between patients who had received interpersonal therapy compared with control in terms of the risk of developing a new episode (RR: 0.92, 95% CI: 0.81–1.05).30 The authors rated the overall quality of evidence for relapse as low, according to the GRADE criteria.30 No studies reviewed by Clarke et al reported on the providers of interpersonal therapy.30 Adverse EventsThis outcome was rarely reported in the systematic reviews. Jakobsen et al stated that 149 of the 4 studies included in their meta-analysis reported adverse events. This was a greater tendency for participants in the treatment-as-usual group to be hospitalized after the end of treatment, but this finding was not statistically significant.46 Quality of LifeThis outcome was not reported in the systematic reviews. Supportive Therapy Compared With Usual Care for Major Depressive DisorderDepressive Symptoms, Treatment Response, and RemissionWe identified 2 systematic reviews that reported results for changes in depressive symptoms after patients had received supportive therapy versus usual care for the treatment of major depressive disorder.14,22 Cuijpers et al conducted a meta-analysis to determine the effectiveness of supportive therapy compared with control (usual care or wait list) (18 studies, N = 899) or pharmacotherapy (4 studies, N = 408) in patients with major depressive disorder.14 Compared with usual care or waitlist control, supportive therapy significantly improved symptoms of depression (SMD: 0.58, 95% CI: 0.45–0.72). However, the authors found no significant difference between supportive therapy and pharmacotherapy (SMD: −0.18, 95% CI: −0.59 to 0.23).14 The authors rated the overall quality of the evidence as low, according to the Cochrane risk-of-bias tool.14 The providers of supportive therapy reported in the studies reviewed by Cuijpers et al were diverse and included nurses, psychiatrists, psychologists, social workers, specialists in counselling, and trained nonspecialists.14 Churchill et al systematically reviewed psychotherapies for the treatment of major depressive disorder and performed an analysis for supportive therapy compared with usual care.22 Of the 4 studies included in this analysis,24,50–52 3 studies24,50,51 were also included in the 2016 systematic review by Cuijpers et al.14 Overall, there was a significant difference in posttreatment recovery (4 studies, N = 118; OR: 2.71, 95% CI: 1.19–6.16]).22 Posttreatment recovery was defined as patients no longer being deemed to have a clinically meaningful level of depression, as indicated by a score of less than 10 on the Beck Depression Inventory or less than 6 on the Hamilton Depression Rating Scale. The authors also found a significant reduction in symptoms for patients who had received supportive therapy versus usual care (4 studies, N = 123; SMD: −0.42, 95% CI: −0.78 to −0.06]).22 The authors reported that the overall quality of evidence was low, based on the Cochrane risk-of-bias tool, owing to low scores on internal validity and inadequate reporting of methodology.22 No studies reviewed by Churchill et al reported on the providers of supportive therapy.22 Adverse EventsThis outcome was not reported in the systematic reviews. Quality of LifeThis outcome was not reported in the systematic reviews. A full summary of the study characteristics and results of all systematic reviews included in this health technology assessment can be found in Appendix 2, Table A2. A summary of the main results is presented in Tables 1a, 1b, and 1c. Table 1a:Summary of Results: Cognitive Behavioural Therapy
Table 1b:Summary of Results: Interpersonal Therapy
Table 1c:Summary of Results: Supportive Therapy
DiscussionCognitive Behavioural TherapyCognitive Behavioural Therapy Compared With Usual CareThree meta-analyses of CBT for the treatment of major depressive disorder indicated that CBT significantly reduced depression symptoms posttreatment compared with usual care.20–22 Three meta-analyses reported results for posttreatment relapse of major depressive disorder following treatment with CBT versus usual care.29–31 Overall, the 3 reviews concluded that CBT significantly reduced the risk of relapse or recurrence compared with usual care.29–31 Two meta-analyses of CBT for the treatment of generalized anxiety disorder indicated that CBT significantly reduced anxiety symptoms posttreatment compared with usual care.11,20 None of the systematic reviews reported on adverse events. One systematic review of CBT for the treatment of generalized anxiety disorder assessed quality of life.11 The difference in mean quality-of-life scores between patients who had received CBT and those who had received usual care was significant, in favour of CBT.11 The overall quality of the evidence within the systematic reviews was generally reported as low. Reasons for this include antidepressants used in control groups being variously described as “treatment as usual” and “clinical management”; varying definitions provided for recovery, recurrence, relapse, and remission; lack of blinding of patients and treatment providers; and several studies excluding from their analyses randomized patients who did not commence treatment or later dropped out. Cuijpers et al performed a meta-analysis of CBT versus usual care with regard to symptom reduction.20 They evaluated the evidence for publication bias and estimated that approximately 14% of major depressive disorder studies and 25% of generalized anxiety disorder studies were missing from their meta-analysis; however, they reported that this did not change the statistical significance of their pooled summary estimates.20 Driessen et al investigated publication bias in the literature on psychological interventions for depression and concluded that the efficacy of psychological interventions in general has been overestimated in the published literature, as it has been for pharmacotherapy.54 The authors stated that both treatments are effective but not to the extent that the published literature would suggest.54 As a result, Driessen et al suggest that funding agencies and journals should archive both original protocols and raw data from studies to allow for the detection and correction of outcome-reporting bias.54 Cuijpers et al commented on the quality of CBT in generalized anxiety disorder studies, finding that not all psychotherapy providers reported using a standard manual and that limited information was provided on treatment components, including those of CBT, and adherence to treatment manuals.38 The authors further stated that the literature on psychotherapy studies for generalized anxiety disorder differs markedly from that for major depressive disorder, in which the same standard treatment manual is used across many studies.38 The systematic reviews rarely reported details about the providers of CBT; in those that did, there was variation in provider type. Cognitive Behavioural Therapy With and Without Pharmacotherapy Compared With Pharmacotherapy OnlyFor the acute treatment of major depressive disorder, Karyotaki et al reported no significant difference in response rates for combined CBT and antidepressants compared with CBT only at up to 6 months and up to 1 year postrandomization.35 Amick et al systematically reviewed second-generation antidepressants compared with CBT for the treatment of major depressive disorder and found no significant difference in response or remission rates.36 Cuijpers et al compared acute-phase CBT (without continuation treatment) with acute-phase pharmacotherapy (with pharmacotherapy continued during follow-up) in patients with major depressive disorder and found no significant difference in outcome (as measured by the number of patients who responded to treatment and remained well) at a 1-year follow-up.37 However, when acute-phase CBT (without continuation treatment) was compared with acute-phase pharmacotherapy that was discontinued during follow-up, there was a significant difference in 1-year outcomes, favouring CBT.37 The systematic reviews did not report on adverse events or quality of life. The overall quality of the evidence within 2 systematic reviews was generally reported as low.35,36 However, Cuijpers et al considered the overall quality of the evidence they reviewed to be “relatively high” compared with the quality of studies on psychotherapy for adult depression in general.37 Details about treatment providers were rarely reported in these systematic reviews. Interpersonal TherapyTwo meta-analyses of interpersonal therapy for the treatment of major depressive disorder indicated that interpersonal therapy significantly reduced depression symptoms posttreatment compared with usual care.21,46 The overall quality of the evidence within the systematic reviews was consistently reported as low. Of note, the feasibility of providing high-quality evidence in psychological studies is difficult, and the issues affecting quality are not easily addressed within the context of randomized controlled trials.22 For example, individual therapist characteristics cannot be controlled for, nor can the nature of the therapeutic encounter be measured with absolute precision.22 The systematic reviews rarely reported on treatment providers. We identified no systematic reviews of interpersonal therapy for the treatment of generalized anxiety disorder that matched our inclusion criteria. Supportive TherapyTwo meta-analyses of supportive therapy for the treatment of major depressive disorder concluded that supportive therapy significantly reduced symptoms of major depressive disorder posttreatment compared with usual care. Cuijpers et al found no significant difference between supportive therapy and pharmacotherapy in reducing symptoms of depression in patients with major depressive disorder.14 Churchill et al found a significant difference in posttreatment recovery favouring supportive therapy versus usual care.22 Adverse events and quality of life were not reported in the systematic reviews. As with interpersonal therapy, the overall quality of the evidence within the systematic reviews was consistently reported as low, based on similar reasons to those discussed for interpersonal therapy, as well as low scores on internal validity and inadequate reporting of methodology.22 The systematic reviews rarely reported on treatment providers. We identified no systematic reviews of supportive therapy for the treatment of generalized anxiety disorder that matched our inclusion criteria. Limitations to This Systematic ReviewThe following limitations apply to our systematic review:
ConclusionsCognitive Behavioural Therapy, Interpersonal Therapy, or Supportive Therapy Compared With Usual Care for Major Depressive Disorder and Generalized Anxiety Disorder
Cognitive Behavioural Therapy With and Without Pharmacotherapy Compared With Pharmacotherapy Only for Major Depressive Disorder
Details About Psychotherapy Providers
ECONOMIC EVIDENCEResearch Questions
MethodsLiterature SearchWe performed an economic literature search on October 28, 2016, for studies published from January 1, 2000, until the search date. To retrieve relevant studies, we used the clinical search strategy with an economic filter. Database auto-alerts were created in CINAHL, Embase, MEDLINE, and PsycINFO and monitored for the duration of the health technology assessment review. We performed targeted grey literature searching of health technology assessment agency websites and clinical trial registries. See Clinical Evidence, Literature Search (p. 11), for further details on methods used. Finally, we reviewed the reference lists of the included economic literature for any additional relevant studies not identified through the systematic search. The literature search strategies, including all search terms, are described in Appendix 1. Literature ScreeningA single reviewer screened titles and abstracts, and, for those studies meeting the inclusion criteria, we obtained full-text articles. For the full-text citations that did not meet the inclusion criteria, we recorded reasons for exclusion. Inclusion Criteria
Exclusion Criteria
Types of ParticipantsThe population of interest was adults (aged 18 years and older) with a new diagnosis or recurrent episode of major depressive disorder and/or generalized anxiety disorder. Types of InterventionsWe compared the following interventions:
Types of Outcomes MeasuresWe examined the following outcomes:
Data ExtractionWe extracted the following data from the included literature:
Study Applicability and Methodological QualityWe determined the usefulness of each identified study for decision-making by applying a modified applicability checklist for economic evaluations that was originally developed by the National Institute for Health and Care Excellence (NICE) in the United Kingdom. The original checklist is used to inform development of clinical guidelines by NICE. We retained questions from the NICE checklist related to study applicability and modified the wording of the questions to remove references to guidelines and to make it Ontario specific. The results of the applicability checklist and our assessment of the methodological quality of the studies included in the economic literature review are presented in Appendices 4 and 5, respectively. Results
Literature SearchThe database and grey literature searches yielded 1,200 citations published between January 1, 2000, and October 28, 2016 (with duplicates removed). We excluded a total of 1,039 articles based on information in the title and abstract. We then obtained the full texts of 161 potentially relevant articles for further assessment. A total of 15 studies met the inclusion criteria and were synthesized to establish the applicability of their findings to the Ontario context. Figure 2 presents the flow diagram for the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) for the economic evidence review. PRISMA Flow Diagram—Economic Evidence Review Abbreviations: CBT, cognitive behavioural therapy; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses. Source: Adapted from Moher et al.19 Review of Included Economic StudiesOf the 15 eligible studies,55–69 14 examined the cost-effectiveness of CBT, 1 examined the cost-effectiveness of interpersonal therapy,58 and none examined the cost-effectiveness of supportive therapy. Nine studies were individual-level cost-effectiveness analyses conducted alongside randomized controlled trials; their sample sizes ranged from 93 to 469 participants.57–60,62,64,66–68 Six economic evaluations were model-based cost-effectiveness analyses.55,56,61,63,65,69 Only 1 model-based cost-effectiveness analysis examined the cost-effectiveness of CBT in patients with generalized anxiety disorder alone55; the rest included populations with major depressive disorder alone or both major depressive disorder and symptoms of anxiety. No studies stated whether patients were diagnosed with generalized anxiety disorder, but some patients were reported to have anxiety. This was not recorded in a systematic way across the studies. Overall, CBT, provided as individual or group therapy, provided as the only therapy or in combination with pharmacotherapy, represents good value for money at different country-specific willingness-to-pay thresholds. The cost-effectiveness of interpersonal therapy, based on 1 study from the Netherlands,58 is uncertain. In line with our two research questions, we next summarize, compare, and contrast study designs with respect to the type, perspective, and time horizon of analysis; study populations; comparative strategies; and study outcomes (i.e., effects or benefits and costs). We also describe the main cost-effectiveness findings. Tables 2a, 2b, and 2c summarize the characteristics and results of the included studies. Table 2a:Results of Economic Literature Review—Summary: Cost-Effectiveness of CBT for the Treatment of Major Depressive Disorder and/or Generalized Anxiety Disorder
Table 2b:Results of Economic Literature Review—Summary: Cost-Effectiveness of Interpersonal Therapy for the Treatment of Major Depressive Disorder
Table 2c:Results of Economic Literature Review—Summary: Cost-Effectiveness of Outpatient Models of Care for Providing In-Person CBT for the Treatment of Major Depressive Disorder and/or Generalized Anxiety Disorder
The Cost-Effectiveness of Cognitive Behavioural Therapy for the Management of Adults with Major Depressive Disorder and/or Generalized Anxiety DisorderStudy DesignSeven trial-based cost-effectiveness analyses (4 from the United Kingdom, 2 from the United States, and 1 from Romania)59,60,62,64,66–68 and 4 model-based cost-effectiveness analyses (2 from the United Kingdom, 1 from Thailand, and 1 from Japan)61,63,65,69 examined the cost-effectiveness of CBT (see Table 2a). PerspectiveStudy perspective depended on the features of each country's health care system; thus, the U.S. studies were conducted from a health care payer's perspective, whereas the majority of the other studies were conducted from a societal perspective or included a societal perspective in a sensitivity analysis. Time HorizonThe duration of follow-up (in trial-based cost-effectiveness analyses) or time horizon (in model-based cost-effectiveness analyses) was short in most studies, ranging from 4 to 24 months, thus not allowing enough time to account for the recurrent and chronic nature of the disorders. PopulationStudies included mixed populations consisting of people with newly diagnosed major depressive disorder and those experiencing recurrent episodes. Therefore, in the majority of the cost-effectiveness analyses we reviewed, the disorder was considered moderate or severe. ComparatorsMost studies compared CBT combined with pharmacotherapy to pharmacotherapy only (i.e., usual care). CBT was provided in the first 4 months of treatment (i.e., in the acute and continuation phases). The total number of in-person CBT sessions in the trial-based cost-effectiveness analyses ranged from 566 to 18,67 and sessions typically lasted 50 to 90 minutes. In the model-based studies, CBT was provided in 10 to 16 weekly sessions, each lasting between 50 and 60 minutes. Outcomes: Effects and CostsIn all model-based61,63,65,69 and 3 trial-based economic analyses,64,67,68 the effectiveness of CBT versus usual care was expressed in adjusted life-year outcomes (i.e., quality-adjusted life-years [QALYs] or disability-adjusted life-years [DALYs]). The other trial-based cost-effectiveness analyses examined the benefit of CBT in terms of clinically relevant health outcomes such as mean changes in depression scale scores from baseline (i.e., symptom improvement),64,66 the number of relapses or recurrent episodes at the end of follow-up,59 and the number of depression-free days.60,62 All studies found improvements in clinical outcomes and incremental gains in QALYs for CBT compared with usual care (see Table 2a). For example, Revicki et al found that the total number of days with depression decreased by 26 with CBT versus usual care (P = .05),60 and Scott et al found a statistically significant 50% reduction in the rate of recurrence at 62 weeks in patients treated with 16 sessions of CBT versus usual care (mean hazard ratio: 0.51, 95% CI: 0.32–0.92).59 In trial-based cost-utility analyses, CBT was associated with an increase in QALYs of between 0.05 and 0.06. In the model-based cost-utility analyses, this increase was between 0.03 and 0.04 QALYs for moderate major depressive disorder and between 0.08 and 0.11 QALYs for severe major depressive disorder.61,63,69 In all studies, the unit costs were adequately assessed, with the majority of cost-effectiveness analyses using a bottom-up approach for calculating costs incurred during the study. Direct medical costs were calculated from the following estimates:
If a societal perspective was applied, costs included the costs of social care services (e.g., costs of social work or social self-help services, home help, employment services) and indirect costs (e.g., costs of travel time to attend therapy, over-the-counter drugs, private or alternative therapies, loss of earnings owing to time off work, disability payments, productivity loss). Incurred costs in the trial-based cost-effectiveness analyses were collected per participant using validated questionnaires for the assessment of resource use and time. All studies provided overall treatment costs, including those for CBT, which incurred greater costs than usual care. In addition, a few studies estimated costs solely applicable to the use of CBT, including the number of sessions and the salary of the CBT provider. For example, Scott et al estimated the mean cost of delivering a 16-session course of CBT to be £1,664 (in 1999 £),59 and Revicki et al estimated the mean cost of delivering an 8-session course of CBT to be US$1,844 (in 2005 USD).60 Cost-EffectivenessAll but one modelling study69 found that, compared with usual care, CBT only or CBT in combination with pharmacotherapy represented good value for money at different country-specific willingness-to-pay thresholds. In modelling studies that favoured CBT over usual care, the probability of cost-effectiveness ranged from 76% to 88% for moderate major depressive disorder and was over 96% for severe major depressive disorder (at a country-specific willingness-to-pay threshold of £30,000 per QALY (United Kingdom)61 or ¥6.75 million per QALY (Japan).63 A model-based cost-effectiveness analysis by Koeser et al produced slightly different results than the other cost-effectiveness analyses we reviewed.69 Koeser et al found lower probabilities of CBT being cost-effective in a cost-effectiveness analysis of CBT versus pharmacotherapy only (20% at a willingness-to-pay threshold of £25,000/QALY) and in a cost-effectiveness analysis of the combination of CBT and pharmacotherapy versus pharmacotherapy only (43%).69 These less favourable estimates may be explained in the following ways. First, the base case population was more severely ill than in the other studies; consequently, the model did not consider no treatment as usual care. Second, the efficacy of CBT only or CBT combined with pharmacotherapy was estimated in a Bayesian meta-analysis that included few randomized controlled trials; consequently, the point estimate was associated with a large degree of uncertainty. This uncertainty regarding the intervention effect propagated throughout the model, resulting in a large degree of uncertainty around the estimate of the incremental cost-effectiveness ratio. The Cost-Effectiveness of Interpersonal Therapy for the Management of Adults With Major Depressive DisorderAmong the studies that met our inclusion criteria, only one compared the cost-effectiveness of interpersonal therapy versus usual care (i.e., no treatment, psychoeducation, or psychoeducation combined with pharmacotherapy). Bosmans et al conducted a 12-month trial-based cost-effectiveness analysis of 143 Dutch adults with major depressive disorder in which 10 sessions of interpersonal therapy were provided over 5 months (see Table 2b).58 Compared with usual care (i.e., no treatment), interpersonal therapy was associated with a statistically significant increase in incremental costs of ζ769 (95% CI: −ζ2,459 to ζ3,433 [in 2003 ζ]) and statistically nonsignificant increments in effects (mean difference: 0.01, 95%CI: −0.08 to 0.10). These results led to a considerable estimate of the incremental cost-effectiveness ratio of ζ76,900 per QALY gained, a large degree of uncertainty regarding this estimate, and the conclusion that interpersonal therapy is not cost-effective at acceptable willingness-to-pay thresholds in the Netherlands. The Cost-Effectiveness of Outpatient Models of Care for In-Person Cognitive Behavioural TherapyStudy DesignOne individual-level economic analysis from the United Kingdom57 and 2 model-based cost-effectiveness analyses from Australia55,56 examined the cost-effectiveness of having in-person CBT provided by different types of provider (Table 2c). The UK study was a cost-minimization analysis that used data from 93 cohort participants of a national psychotherapy service trust.57 PerspectiveAll studies used a health care payer's perspective. Time HorizonThe time horizon was 3 months in the individual-level cost-minimization analysis57 and 5 years in the model-based cost-effectiveness analyses.55,56 PopulationThe study population of the individual-level cost-minimization economic analysis was adults with major depressive disorder.57 The base case populations for the model-based analyses had either major depressive disorder56,57 or generalized anxiety disorder.55 ComparatorsThe UK study directly compared the costs of providing CBT as 6 to 18 weekly individual sessions with the costs of providing CBT in 10 to 12 weekly group sessions including 8 to 12 participants.57 The 2 Australian model-based cost-effectiveness analyses compared 5 to 7 interventions55,56:
Outcomes: Benefits and CostsThe largest benefits, expressed in terms of years of life lost and DALYs, were associated with the following55,56:
The smallest increment in costs was found for CBT provided as group therapy by publicly funded therapists.55,56 A 3-month analysis from the United Kingdom found no statistically significant difference in total costs between group and individual CBT.57 Cost-EffectivenessIn the cost-effectiveness analysis, both group CBT and individual CBT for the treatment of major depressive disorder or generalized anxiety disorder were associated with a favourable estimate of the incremental cost-effectiveness ratio (ICER) of AU$10,000 per DALY when provided by a publicly funded psychologist.55,56 Applicability and Methodological Quality of the Included StudiesWe deemed 11 studies partially applicable to our research question, as they had some similarities to our base case population and comparators. The major differences were a short duration of follow-up and a lack or inclusion of patients with mild disease. However, none of the studies was done in Canada or Ontario; thus, the results of the cost-effectiveness analyses cannot be directly translated to the Ontario context owing to differences in health care systems. Appendix 4 describes the applicability of the included studies to the context of Ontario's health care system and to our study objectives. We found that the majority of studies had important limitations, particularly in terms of the assessment of all important health outcomes, the inclusion of all relevant comparators, the relatively short duration of the time horizons used, and the lack of exploration of uncertainty and its influence on the studies' cost-effectiveness estimates. Appendix 5 outlines the methodological limitations of the examined studies. DiscussionOur evidence synthesis found that CBT is the most researched psychological therapy for the management of major depressive disorder and generalized anxiety disorder. In the majority of the cost-effectiveness evaluations we reviewed (9 trial-based and 5 model-based), and as compared with usual care, we found that CBT only or in combination with pharmacotherapy represents good value for money for adults with major depressive disorder and/or generalized anxiety disorder at various country-specific willingness-to-pay thresholds. At these thresholds, CBT was found to have a greater than 90% likelihood of being cost-effective for people with severe or recurrent major depressive disorder. However, the cost-effectiveness of structured in-person CBT in populations with mild major depressive disorder or generalized anxiety disorder is largely unknown owing to a lack of economic studies in these populations or our restrictive inclusion criteria regarding the use of computerized CBT. Evidence is scarce regarding the cost-effectiveness of interpersonal therapy, another regularly used structured psychological therapy for people with major depressive disorder. We identified only 1 trial-based study58; this was conducted in the Netherlands with a small sample of 143 patients with major depressive disorder. It suggested that interpersonal therapy may not be more efficient than usual care (defined as no treatment, psychoeducation, or psychoeducation combined with pharmacotherapy). In addition, no economic evaluation examined the cost-effectiveness of supportive therapy. Lastly, limited and mixed evidence exists regarding the cost-effectiveness of CBT provided by different types of health care professionals, either as individual or as group therapy. While a 3-month trial-based cost-minimization analysis in 93 adults with major depressive disorder suggested no differences in the mean costs between individual and group CBT,57 2 Australian economic studies suggested that group CBT, provided either short term or long term, by publicly funded psychologists represented good value for money.55,56 ConclusionsMajor depressive disorder and generalized anxiety disorder are among the most commonly diagnosed mental illnesses in Canada and are associated with a high societal and economic burden.71–75 Access to cost-effective psychological treatments in Ontario is needed to optimize care.76–78 We evaluated a relatively large number of economic analyses in this review. However, none of the economic analyses was done from the perspective of Ontario or Canada, and many studies had methodological limitations. PRIMARY ECONOMIC EVALUATIONThe published economic evaluations identified in the literature review addressed the cost-effectiveness of structured psychological therapies (CBT or interpersonal therapy), as the only therapy or in combination with pharmacotherapy, for the management of major depressive disorder and/or generalized anxiety disorder in adults, but none took a Canadian or Ontario perspective. Owing to this limitation, we conducted a primary economic evaluation to determine whether in-person structured psychological treatment provided by publicly funded, regulated health care professionals for the management of major depressive disorder and/or generalized anxiety disorder in adult outpatients represents good value for money from the perspective of the Ontario Ministry of Health and Long-Term Care. Research Question
MethodsThe information presented in this report follows the reporting standards set out by the Consolidated Health Economic Evaluation Reporting Standards Statement.79 Our methodological approaches follow the recent recommendations set out by the fourth edition of the Canadian Agency for Drugs and Technologies in Health (CADTH) Guidelines for the Economic Evaluation of Health Technologies: Canada80 and align with Health Quality Ontario's Health Technology Assessments Methods and Process Guide.16 Type of AnalysisWe conducted cost-effectiveness and cost-utility analyses. Our cost-effectiveness analyses assessed the cost per recurrent episode or per hospitalization avoided and the cost per life-year saved. Our cost-utility analysis assessed the cost per QALY gained. Target PopulationThe study population was newly diagnosed adult outpatients aged 18 to 75 years with a primary diagnosis of major depressive disorder alone or in combination with generalized anxiety disorder. Major depressive disorder has an episodic nature.81,82 In clinical practice, people with mild major depressive disorder follow a different clinical pathway than those with moderate to severe major depressive disorder. As suggested by the clinical experts we consulted, we defined the baseline severity of a major depressive episode by the score on the 9-item Patient Health Questionnaire (PHQ-9),83 which corresponds to the 9 diagnostic criteria of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).71,84–87 Mild major depressive disorder corresponds to a PHQ-9 score of between 10 and 14, and moderate to severe major depressive disorder corresponds to a PHQ-9 score of more than 14. In addition to the DSM-5 criteria, the diagnosis of generalized anxiety disorder corresponds to a score equal to or greater than 10 on a 7-item generalized anxiety disorder scale called the GAD-7.88 It is worth noting that although anxiety disorders can exist in isolation, at least half the time, generalized anxiety disorder coexists with major depressive disorder.89–91 Therefore, in our base case analysis, our target population consisted of people with both major depressive disorder and generalized anxiety disorder; in our scenario analysis, we examined people with generalized anxiety disorder only. We excluded some populations with depression from our analysis owing to important differences in treatment pathways92,93:
PerspectiveWe conducted this economic analysis from the perspective of the Ontario Ministry of Health and Long-Term Care. InterventionsCognitive Behavioural TherapyThe base case analysis examined the cost-effectiveness of CBT as the most commonly used and researched psychological treatment for major depressive disorder. CBT is often provided through 8 to 20 initial sessions over the first 4 months following diagnosis with several follow-up sessions provided during the maintenance phase.89,90,94,95 CBT with continuous and interactive clinician engagement can be delivered as a structured, face-to-face therapy, as a remote, interactive therapy (via phone, teleconference, or Internet-based technologies such as Skype), or as a computer-delivered self-help therapy.71,84–87 Our analysis focused on the structured face-to-face approach to CBT, delivered as either individual or group therapy by a publicly funded, regulated (registered and professionally trained) health care professional (physician or nonphysician). Based on expert consultation, in the base case analysis, we assumed that CBT is provided in 14 weekly sessions, lasting an hour if provided by an individual therapist or 2 hours if provided as group therapy. The training of nonphysician therapists is regulated by professional organizations in Ontario. Based on expert consultation, we also assumed that CBT provided by regulated nonphysician therapists (e.g., nurses, occupational therapists, psychologists, psychotherapists, social workers) is administered with no difference in terms of resource time or labour costs (i.e., salaries). Interpersonal TherapyInterpersonal therapy is often provided on an individual basis and delivered over 6 to 20 sessions.96 Therefore, we conducted a scenario analysis to examine the cost-effectiveness of interpersonal therapy in the initial treatment phase, assuming the same delivery options and number of sessions as for CBT.71,84–87 PharmacotherapyIn addition to psychological treatments, and depending on disease severity, another common treatment option for noncomplex major depressive disorder (i.e., major depressive disorder that is not treatment-resistant) is pharmacotherapy (i.e., antidepressants, including selective serotonin reuptake inhibitors [SSRIs], such as sertraline, and serotonin–norepinephrine reuptake inhibitors [SNRIs], such as venlafaxine).2,8–10 Generalized anxiety disorder is treated with similar medications to those used for noncomplex major depressive disorder. In the case of treatment-resistant major depressive disorder (a complex form of major depressive disorder), pharmacotherapy is often combined with brain intervention therapies. Examples of such therapies include electroconvulsive therapy, transcranial magnetic stimulation, and magnetic seizure therapy.71,84–87 Given the similarity of treatment pathways for major depressive disorder and generalized anxiety disorder, and the fact that many people experience both major depressive disorder and generalized anxiety disorder, our modelling approach focused on representing the natural and clinical course of major depressive disorder. In addition, and based on current clinical practice (as established through expert consultation), first and recurrent episodes of major depressive disorder are handled in the same way: CBT only or with pharmacotherapy, depending on the episode severity. Table 3 summarizes the interventions we evaluated in the economic model. The intervention and usual-care strategies depended on the severity of the major depressive disorder episode. Newly diagnosed adults followed different clinical treatment pathways depending on the severity of the episode; that is, whether it was mild or moderate to severe. Mild episodes were considered to be treated with CBT only, whereas mild to moderate episodes were considered to be treated with a combination of CBT and pharmacotherapy, based on recommendations set forth by the 2016 Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines.2,8–10 For adults with mild major depressive disorder, usual care was no psychological therapy, and for those with moderate to severe major depressive disorder, usual care was pharmacotherapy. Pharmacotherapy was initiated with the lowest daily dose of sertraline, in accordance with the 2016 CANMAT guidelines71,84–87 and clinical practice (as established through expert consultation). Table 3:Interventions and Comparators Evaluated in the Primary Economic Model
Outcomes of Interest
Discounting and Time HorizonFollowing the 2017 CADTH guidelines, we applied an annual discount rate of 1.5% to both costs and QALYs in the base case analysis.80 We used a 5% discount rate in the sensitivity analysis. All costs are expressed in 2017 Canadian dollars.97 The time horizon for the base case analysis was 5 years. Due to the episodic nature of major depressive disorder, we deemed a 5-year time horizon was long enough to capture both the initial and downstream costs associated with the management of newly diagnosed and recurrent noncomplex major depressive disorder. Model StructureWe developed a state-transition (Markov) probabilistic microsimulation (individual-level) model to evaluate CBT treatment options for a hypothetical cohort of women and men aged 18 years and older diagnosed with a first episode of major depressive disorder. Our mathematical model simulated the clinical course of major depressive disorder by severity of the initial episodes in each of the 1,000 hypothetical adult patients (Figure 3). The initial age of the hypothetical patients ranged between 18 and 75 years (mean = 33 years) and was separately drawn for each individual from a truncated normal distribution. We tracked overall survival, quality-adjusted survival, number of recurrent episodes, number of hospitalizations, number of deaths as a result of suicide, and costs over the first 5 years following a person's diagnosis of major depressive disorder in the base case, and over longer time frames in scenario analyses (i.e., 10 years, 20 years, and lifetime or until age 100 years). Model Structure Abbreviation: MDE, major depressive episode. This figure depicts an individual-level (microsimulation) Markov model that includes 11 health states, each represented by an oval, reflecting the course of mild or moderate to severe major depressive disorder. The simulation starts with a hypothetical patient aged between 18 and 75 years (age is drawn from a distribution) with a first mild or moderate to severe major depressive episode. In each 1-week cycle, a patient has a chance to move among health states. Death is an absorbing Markov health state. The model accounts for the age of major depressive disorder onset, counts the number of recurrent events, and modifies the risk of future major depressive episodes and changes in treatment accordingly. It takes into account the probability of death as a result of suicide according to the severity of disease and the probability of hospitalization in the complex depression health state. Transfer to the complex depression health state depends on the number of prior major depressive episodes (n ≥ 3). “p_dropout” denotes the probability of dropping out in the acute-phase states for patients with either a mild or moderate to severe major depressive episode; “p_well” and “p_complex” denote the probabilities of transferring to the well or complex depression health states, respectively, after dropping out in the acute phase; “p_relapse” denotes the probability of relapse and is related to a change in health state (e.g., from mild to moderate major depressive disorder) and change in treatment; “p_no response” in the maintenance phase for a patient with moderate or severe major depressive disorder triggers an increase in dose of antidepressant or a switch from sertraline to venlafaxine; “p_recurrence” denotes the probability of recurrence modelled in different health states, with “n_MDE” denoting a tracker variable that counts a number of recurrent major depressive episodes. According to clinical guidelines, the course of major depressive disorder consists of the initial phases (i.e., the acute and continuation phases, each lasting approximately 3 months), during which response and relapse are monitored and the goal is to achieve remission, and the maintenance phase (lasting approximately 6 to 24 months, with an average 9 to 12 months), during which full recovery can be established or recurrence of a full major depressive episode can occur.2,8–10 According to the DSM-5, relapse is a new episode of major depressive disorder that occurs once a person has achieved remission during the continuation phase. In contrast, recurrence is a new episode of major depressive disorder that occurs in the maintenance phase after a person has achieved a period of remission including at least 2 months with no significant symptoms.2,8–10 Since relapse and recurrence affect the risk of experiencing another major depressive episode and the potential need for changes to treatment,84,86 a distinction between the initial and maintenance phases is required for modelling purposes. Therefore, we used a short weekly cycle to monitor changes in the progression of disease and adequately reflect what is being done in current clinical practice:
As presented in Figure 3, the model simulates the course of major depressive disorder through a series of transitions among 11 different Markov health states:
During each 1-week cycle, patients may stay within a single health state or move among health states. Note, however, that once in health state 11, death, a patient can no longer transition to another state. The initial depression-phase health states are the acute phase (12 weeks), the continuation phase (12 weeks), and the maintenance phase (up to 24 weeks), during which treatment may be applied, and response, remission, relapse, and recurrence are monitored. These initial health states are categorized by the initial severity of the major depressive episode as mild or moderate to severe, which allows for the possibility of changes in the severity of the initial episode during the acute and continuation phases. It also allows for the consequent addition of pharmacotherapy to CBT for patients initially diagnosed with mild major depressive disorder who progress to moderate or severe and for the dose of sertraline to be increased from 50 mg/day to 100 mg/day in patients whose symptoms are not improving (no response). Patients who do not respond well to an increased dose of sertraline are switched to venlafaxine (75 mg/day), as per expert consultation and the 2016 CANMAT guidelines.84 The frequency of disease progression monitoring (by a general practitioner or psychiatrist) depends on the initial disease severity; in general, monitoring occurs every 2 weeks in the first 4 months and monthly thereafter for the remainder of the first year after a diagnosis of major depressive disorder. In the first 3 months (i.e., during the acute phase), a hypothetical patient has a chance of dropping out, after which they have a chance of either recovering (transferring to the well health state) or deteriorating (either committing suicide or transferring to the complex depression health state). If a patient achieves full remission and remains stable during the maintenance phase, they enter the well health state, in which patients are considered to remain stable (without depression and receiving no treatment but having 2 follow-ups a year with a general practitioner). A patient has a chance of experiencing a recurrent episode from any of the following health states:
In line with the literature findings, we modelled the effects of prior major depressive episodes and the age at disease onset on the risk of episode recurrence. We also assumed that a patient could have a maximum of 2 recurrent major depressive episodes before being considered to have complex or treatment-resistant depression, at which point they would be transferred into the complex depression state, which accounts for hospitalization and secondary psychiatric inpatient care. Finally, each week, based on the lifetime probabilities of Ontario's population, a patient has a chance of dying from all causes from any of the 10 modelled health states. Main AssumptionsThe major structural model assumptions were as follows:
Clinical Outcome and Utility ParametersWe used a number of different input parameters to populate the model. These parameters were used to describe the natural history and clinical course of a newly diagnosed or recurrent major depressive episode, including factors affecting the risk of recurrence (e.g., age at disease onset, number of prior episodes), changes in the severity of initial disease (mild to severe major depressive disorder) and consequent changes in treatment options following a transition from mild to moderate or severe disease. To estimate the cost-effectiveness of CBT versus usual care, we populated the model with parameters related to the efficacy of CBT, health state utilities, and costs. Natural HistoryTo model the natural history of major depressive disorder, we used the literature sources and data from current clinical practice provided through expert consultation (Table 4). The distributions of mild versus moderate to severe cases of major depressive disorder were based on 2 studies.74,99 For newly diagnosed major depressive disorder, we used data from a modelling study by Ferrari at al, which examined the burden of major depressive disorder globally and meta-analyzed the proportions of national U.S., UK, and Australian epidemiologic studies conducted in general populations.74 For recurrent disease, we used data from a large cohort study (the Netherlands Mental Health Survey and Incidence Study [NEMESIS]) that examined the recurrence of major depressive disorder over 20 years and provided a distribution of major depressive disorder by disease severity in people with recurrent disease.99 Table 4:Input Parameters Associated With the Natural History of Major Depressive Disorder: Probabilities and Risks
The probabilities of dropout and response to CBT only or in combination with pharmacotherapy were based on meta-analyses conducted within the most recent UK modelling analysis in people with moderate to severe major depressive disorder.69 After dropout, major depressive disorder could resolve on its own or become more severe; complex depression could end with suicide. In the base case analysis, rates of recurrence were based on 10-year survival curves using data from a large U.S. prospective population-based cohort study with 23 years of follow-up, which included 1,831 participants with first or recurrent episodes.100 In the sensitivity scenario analysis, we used the rate of recurrence over 20 years reported in the NEMESIS study.99 Based on literature findings and expert opinion, we modelled recurrence risks as decreasing with each additional year of age at onset (RR: 0.96, 95% CI: 0.93–0.99)100 and as increasing with each prior major depressive episode (RR: 1.18, 95% CI: 1.06–1.31).101 After a third recurrence, a patient would enter the complex depression state. In this state, the hospitalization rate was modelled using recently published Ontario data.95 Lastly, our model accounted for age-dependent background mortality in Ontario and also for differences in suicide rate based on the severity of major depressive disorder (Table 4). Suicide rates were based on 2 U.S. Food and Drug Administration analyses of clinical trial data.102,103 Intervention EffectsThe clinical review determined the efficacy of CBT. Here, we briefly describe the studies that provided the input parameters for our base case and scenario analyses (Table 5). Table 5:Summary Efficacy Estimates Used in the Economic Model
The efficacy of CBT or interpersonal therapy versus that of usual care was derived from a systematic review of 16 randomized controlled trials conducted by Biescheuvel-Leliefeld et al.29 Usual care was defined as routine clinical management, assessment only, no treatment, or wait list and corresponds to our model's “usual care” arm in patients with mild major depressive disorder. This was a recent systematic review, appraised as being of very good methodological quality (see clinical review); moreover, it examined major depressive disorder recurrence among important clinical outcomes. We established the efficacy of CBT combined with pharmacotherapy (i.e., sertraline as first-line therapy) based on a recent systematic review by Amick et al, which we determined to be of very good methodological quality.36,105 The authors combined data from 3 randomized controlled trials to determine the efficacy of second-generation antidepressants versus a combination of second-generation antidepressants and CBT on achieving full remission in adults with major depressive disorder. We established the efficacy of second-generation antidepressants from a systematic review and network meta-analysis by Cipriani et al, which included 117 randomized controlled trials that compared the efficacies of 12 second-generation antidepressants on major depressive disorder.106 We derived the difference in the effects of individual versus group CBT from a 2001 systematic review by Churchill et al that evaluated major depressive episode recurrence in 6 randomized controlled trials.22 To estimate a risk ratio, we adjusted the reported odds ratio (1.98, 95% CI: 1.11–3.54) using the mean probability of major depressive episode that was calculated from the control arm data reported in a systematic review of randomized controlled trials by Williams et al.107 We based the efficacy of CBT versus usual care for generalized anxiety disorder on a systematic review published in 2016, which meta-analyzed reductions in mean generalized anxiety disorder symptom scores from 31 studies and reported a Hedge's g statistic of 0.80 (95% CI: 0.67–0.93).20 As this was the only clinical outcome reported in the study, we assumed that it represented remission in patients with generalized anxiety disorder, and we recalculated the risk ratio using the recommended method.108 Finally, we accounted for a possible reduction in the effect of CBT owing to publication bias, as suggested by a methodological study that analyzed the results of 61 grants funded by the National Institutes of Health examining the effects of psychological treatments on major depressive disorder published between 1972 and 2008 (see Table 8, Analysis).54 Table 8:Cost Calculations Used in Scenario Analysis: CBT Provided by GP as Individual or Group Therapy
Health State UtilitiesWe specified a quality-of-life utility (weight) for each health state to calculate quality-adjusted life-years (QALYs). A QALY is a measure that jointly accounts for changes in both quantity and quality of life (morbidity).109 A utility is a measure of health-related quality of life and reflects the strength of preference for specified health states. By convention, utilities are anchored on death and best possible health (death is assigned a utility weight of 0, and perfect health is assigned a utility weight of 1).109 The value of a QALY for a certain health state is calculated by multiplying time spent in that health state with the utility assigned to that health state (e.g., 1 year of untreated major depressive disorder with a utility weight of 0.7 equals a QALY of 0.7). The utilities used in our analysis are presented in Table 6. We derived the majority of these using the standard gamble method.110–113 A 2014 systematic review by Mohiuddin and Payne examined 35 studies and meta-analyzed the utility values elicited in adults with major depressive disorder.110 We based our utility values for untreated depression (categorized by severity) on the values presented in this study. For the “continuation” and “maintenance” Markov health states, we used the treatment-related utility values elicited from a UK study of 457 adults with major depressive disorder and generalized anxiety disorder receiving a psychological therapy114 or from a study of 70 North American adults undergoing pharmacotherapy with imipramine.111 Table 6:Health State and Intervention Utilities Used in the Economic Model
We accounted for decreases in health-related quality of life owing to prior major depressive episodes. Thus, in the 2 recurrent major depressive episode Markov states (mild and moderate to severe), we used utility weights determined for Canadian patients with past mild or moderate to severe major depressive episodes.112 The utility value during the acute phase of a recurrent, mild or recurrent, moderate to severe major depressive episode (< 6 months) was a product of the weights assigned for the corresponding severity levels of the past and new episodes (e.g., annual utility for the recurrent, moderate to severe health state: 0.52 × 0.67). In the Markov well health state, patients were assumed to be stable and not receiving treatment. Lenert et al conducted a mapping study using a sample of 295 patients with major depressive disorder to provide the standard gamble utility weights for those who are “near normal health.”113 In the complex depression health state, we assigned the weights elicited in 114 patients in the United Kingdom with severe major depressive disorder in the acute phase of treatment.115,116 During the event of hospitalization, we assigned a one-time disutility elicited from patients with severe, treatment-resistant major depressive disorder at high risk of suicide and hospitalization.115,116 Cost ParametersWe estimated the direct medical costs associated with the model strategies using the cost estimates presented in Table 7. Table 7:Costs Used in the Economic Modela: Interventions, Usual Care, Follow-Ups, Complex Depression, and Hospitalization
The costs of CBT treatment consisted of the following:
In the base case analysis, we took a conservative approach and used the unit costs associated with the highest applied hourly rates estimated for publicly funded nonphysician professionals on salary and the fee-for-service physician costs claimed by a psychiatrist. In addition, we chose a psychiatrist to represent the physician force trained for psychotherapy and able to provide structured CBT. However, in the scenario analysis, we tested an assumption that a trained general practitioner could provide structured CBT, including it within the fee-for-service Ontario Health Insurance Plan (OHIP) codes assigned for counselling services (OHIP codes K013, K040).117 The structured face-to-face approach to CBT consists of 14 sessions delivered as individual therapy (1 hour a week to 1 person) or as group therapy (2 hours a week to a group of 12 people). Therefore, we calculated the cost of 1 course of CBT provided by a nonphysician or physician as the product of the number of sessions (14) and the applied hourly salary (for nonphysicians) or fee-for-service costs (for physicians) adjusted for the time spent on a session (1 hour for individual versus 2 hours for group). Next, we explain the calculations of the labour costs for nonphysicians after adjustment for clinical work. We based the salary ranges of publicly funded, regulated therapists (i.e., nurses, occupational therapists, psychologists, psychotherapists, and social workers) on data from literature118–121 and information provided through expert consultation. The average annual salary for publicly funded psychotherapists ranges between $110,000 and $130,000, with benefits ranging between 17%122 and 30%.123 To estimate the labour costs associated with clinical activities, we calculated an applied hourly salary. Applied cost recognizes that salaried clinicians spend time on nonpatient activities, so less than 100% of a clinician's time accounts for clinical work.124 It is recognized that the applied rate (i.e., the ratio of applied time to total time) is 85% for medical staff. Using this applied rate, we calculated applied hourly salaries for publicly funded therapists for the base case and scenario analyses. A similar number of hours per year (i.e., 1,657 hours per year for a full-time nurse) has been previously used in labour cost estimations.124 The following provides an example of our calculations:
We based the costs of follow-up by physicians on the fee-for-service schedule and number of visits. As per the 2016 CANMAT guidelines84 and expert consultation, the number of follow-up visits depended on the severity of a patient's major depressive disorder:
We based drug costs on the costs assigned in the Ontario Drug Benefit program,125 after accounting for dispensing fees and markup costs, as suggested in the literature.126 We estimated the costs of complex depression from data reported in a Health Quality Ontario health technology assessment on the use of electroconvulsive therapy for the management of treatment-resistant depression.127 These estimates are within the range of published cost estimates for a high-cost mental health patient and were generated from Ontario health administrative data.128 We based the costs of hospitalization (estimating a 10-day period for this population) on data from a Canadian cost-effectiveness analysis by Bereza et al conducted in adults with generalized anxiety disorder.129 For the cost of follow-up in patients who are stable (i.e., those in the well health state), we assumed 2 check-ups a year with a general practitioner. Finally, we tested how changing the frequency of follow-up (with psychiatrists and general practitioners) affected the cost-effectiveness results in a scenario analysis. In the separate scenario analysis, we assumed that a general practitioner could provide CBT and estimated the costs of individual or group CBT using available OHIP codes (Table 8). However, there is no OHIP fee code for group therapy for 12 people when provided by a general practitioner. For the scenario of CBT delivered by a general practitioner as individual or group therapy, we thus calculated a ratio of 2.77 from differences in the fee-for-service costs between group psychotherapy for 2 people (OHIP code 208: $40.15117) and group psychotherapy for 6 to 12 people (OHIP code 205: $14.45117). We applied this ratio to the individual therapy costs to estimate the cost of group therapy, as shown in Table 8. In summary, we estimated the total cost of 14 individual CBT sessions conducted by a general practitioner to be $1,215.80, with a weekly cost of $86.84, and we estimated the total cost of 14 group CBT sessions conducted by a general practitioner to be $885.40, with a weekly cost of $63.24. AnalysisWe estimated all outcomes using probabilistic sensitivity analysis, as recommended by the 2017 CADTH economic evaluation guidelines80 and decision-modelling guidelines.131–134 Probabilistic sensitivity analysis is an advanced method that handles parameter (second-order) uncertainty and nonlinear relationships among model parameters (which are often present in Markov models). Parameter uncertainty is handled by setting distributions for input model parameters (see Tables 4 to 7). We assigned distributions for input parameters and repeatedly sampled from those distributions (see Tables 4 to 7). For example, we specified the beta distribution for utilities, the normal distribution for the effect measure of treatment efficacy (i.e., the log-odds ratio), and the gamma distribution for costs. The probabilities of recurrence or death were modelled as time or age dependent. We simulated 1,000 trials, each of which included 1,000 patients, to obtain the mean expected costs and effects of the compared strategies. As it accounts for parameter and decision uncertainty, probabilistic sensitivity analysis generates more accurate estimates of the mean expected effects and mean expected costs than deterministic analysis, and these estimates are used to calculate the ICER. The results of the probabilistic sensitivity analysis were presented in the cost-effectiveness plane by plotting simulated ICER values. The meaning of the ICER depends on the quadrant(s) of the cost-effectiveness plane in which the ICER resides.131,135 A strategy is considered cost-effective if it is associated with greater expected effects and greater expected costs and if the ICER is below the maximum price that a decision-maker or society is willing to pay for an extra unit of effect.135,136 Although the value of the willingness-to-pay threshold remains controversial,137,138 we used a threshold of $50,000 per QALY gained139 and also examined a threshold of $100,000 per QALY gained. A strategy is considered cost-saving (i.e., below a given willingness-to-pay threshold) if it is associated with greater expected effects and lower expected costs. A strategy is considered dominated by another one if it is associated with lower or equal expected effects for higher or equal expected costs.136 We also used cost-effectiveness acceptability curves to graphically present uncertainty in the ICER.140 These curves show the probability of one alternative being cost-effectiveness over another across a range of willingness-to-pay thresholds ($0 to $100,000/QALY gained). We conducted 2 types of base case cost–utility analysis using the probabilistic sensitivity analysis method:
Our sensitivity analysis consisted of 19 scenarios that were calculated using probabilistic sensitivity analysis. A description of all scenarios is presented in Table 9. For example, we examined the cost-effectiveness of interpersonal therapy (scenario 3), the change in cost-effectiveness estimates if the efficacy of CBT were reduced by 25% (scenario 4), and the change in cost-effectiveness estimates if the number of CBT sessions were only 6 (scenario 11). We used both ICER and incremental net benefit estimates to indicate the cost-effectiveness of the compared strategies. A positive incremental net benefit indicates that a strategy is cost-effective. For all scenarios, we assumed a willingness-to-pay threshold of $50,000 per QALY gained. Table 9:Sensitivity Analysis: Description of Structural and Parameter Assumptions in Probabilistic Sensitivity Analysis Scenarios
We conduced all analyses using TreeAge Pro 2017 (TreeAge Software, Williamstown, MA) and Excel 2013 (Microsoft, Redmond, WA). GeneralizabilityThe findings of this economic analysis are generalizable to outpatient adults with mild to severe major depressive disorder and/or generalized anxiety disorder, but they may not be generalized to adults with resistant and complex depression who are at high risk of suicide or are being treated with multiple and complex interventions. These findings may, however, be used to guide decision-making about the specific patient populations in Ontario addressed in the studies evaluated by Health Quality Ontario. Expert ConsultationThroughout the development of this model, we sought expert consultation. The role of the expert advisors was to review the model structure and inputs to confirm that the information we used reasonably reflects the clinical context for major depressive disorder and generalized anxiety disorder in Ontario. However, the statements, conclusions, and views expressed in this report do not necessarily represent the views of the consulted experts. ResultsIn sections below, we present the results of our primary economic evaluation: the base case and sensitivity analyses. Base Case AnalysisTable 10 describes the differences in clinical outcomes among compared strategies assessed through the base case analysis. Tables 11 and 12 present the results of the cost–utility analysis. Table 10:Life Expectancy, Major Depressive Episode Recurrence, Death as a Result of Suicide, and Hospitalization Over 5 Years: Usual Care Versus CBT Strategies
Table 11:Cost–Utility Analysis of Individual or Group CBT Delivered by Different Providers Versus Usual Carea
Table 12:Cost–Utility Analysis: Individual or Group CBT After the Exclusion of Dominated Strategiesa
In terms of clinical outcomes, over a 5-year time horizon, individual CBT increased undiscounted survival (i.e., overall survival or life expectancy) by 0.00278 years (1.015 days) versus usual care, and group CBT increased undiscounted survival by 0.00151 years (0.55 days) versus usual care (see Table 10). Individual and group CBT decreased the number of recurrent major depressive episodes by 0.09 and 0.04, respectively, and reduced the probability of hospitalization by 1.62% and 1.41%, respectively. In the cost-effectiveness analysis applying the incremental changes in these clinical outcomes and the incremental costs from Table 11, we found the following:
1. Cost–Utility Analysis: All Cognitive Behavioural Therapy Strategies Versus Usual CareAs shown in Table 11, compared with usual care, all CBT strategies were associated with ICERs less than $50,000 per QALY gained. CBT provided as group therapy by a nonphysician was associated with the lowest ICER. Compared with usual care, CBT provided as group therapy by a nonphysician was associated with an increased discounted survival of 0.11 QALYs (95% credible interval [CrI]: 0.03; 0.22) and increased discounted mean costs of $401 (95% Crl: −$1,177; $1,665), yielding an ICER of $3,715 per QALY gained. In contrast, CBT provided as individual therapy by a physician was associated with the increments in discounted effects of 0.12 QALYs (95% Crl: 0.03; 0.25) and discounted mean costs of $5,310 (95% Crl: $2,539; $8,938), yielding an ICER of $43,443 per QALY gained. Compared with usual care, CBT provided either as group or individual therapy had high probabilities of cost-effectiveness for the majority of providers. At a $50,000/QALY threshold, these probabilities were 54.8% (individual CBT provided by a physician), 81.2% (individual CBT provided by nonphysicians), 92.7% (group CBT provided by physicians), and 99.5% (group CBT provided by nonphysicians). Individual CBT provided by physicians had an 87.8% likelihood of being cost-effective at the very high willingness-to-pay threshold of $100,000 per QALY. Figure 4 shows cost-effectiveness acceptability curves that graphically represent the probabilities of the examined CBT strategies being cost-effective (compared with usual care) over a wide range of willingness-to-pay thresholds. Cost-Effectiveness Acceptability Curves: Examined CBT Strategies Versus Usual Care Cost-effectiveness acceptability curves graphically present the probability of the 4 examined CBT strategies being cost-effectiveness versus usual care (i.e., no CBT) across various willingness-to-pay thresholds on the x–y coordinate system. The x-axis shows the probability of cost-effectiveness (range: 0–1), and the y-axis shows various willingness-to-pay thresholds (range: $0–$100,000 per QALY gained). 2. Cost–Utility Analysis: Best-Ranked Cognitive Behavioural Therapy StrategiesIn this analysis, we excluded the 2 dominated strategies from Table 11 (i.e., group and individual CBT provided by physicians), as these were associated with equal benefits but higher costs than the nonphysician-administered strategies. Table 12 ranks the 3 remaining strategies by increasing costs and shows that, of all 3 options, group CBT provided by nonphysicians is optimal, as this strategy provides good value for money at a very low willingness-to-pay threshold (e.g., $20,000/QALY). As shown in Figure 5, there was little uncertainty regarding the cost-effectiveness of the group CBT strategy. Thus, in 745 of 1,000 simulations, group CBT provided by nonphysicians was associated with better clinical outcomes and greater costs than usual care, but at a willingness-to-pay threshold below $50,000 per QALY. Group CBT provided by nonphysicians was associated with greater QALYs and lower costs than usual care in 250 simulations (i.e., it was found to be dominant or cost-saving). This strategy was also associated with greater health benefits and costs, but at a threshold above $50,000 per QALY (i.e., it was found not to be cost-effective) in 4 of 1,000 simulations. Scatter Plots of 1,000 Simulated Pairs of Incremental Costs and Effectiveness (QALYs) in the Cost-Effectiveness Plane: Group CBT Provided by Nonphysicians Versus Usual Care Abbreviations: CBT, cognitive behavioural therapy; ICER, incremental cost-effectiveness ratio; WTP, willingness-to-pay threshold ($). All costs are in 2017 Canadian dollars and discounted at 1.5%. Effectiveness is expressed in quality-adjusted life years (QALYs). Negative QALYs indicate that the CBT strategy was associated with worse quality-adjusted survival, and negative costs indicate that the CBT strategy saved money relative to usual care. The diagonal grey line indicates a willingness-to-pay threshold of $50,000 per QALY. The incremental cost-effectiveness ratio ($3,715/QALY gained) is the slope of a straight line from the origin that passes through the (0.11 QALY, $400) coordinate. A 95% confidence ellipse covers 95% of the estimated joint density and was used to represent uncertainty around the incremental cost-effectiveness ratio estimated in the probabilistic sensitivity analysis. In addition, compared with group CBT provided by nonphysicians, individual CBT provided by nonphysicians was associated with a small increase in discounted mean survival of 0.01 QALYs (95% CrI: 0.0001; 0.24) and a significant increase in discounted mean costs of $2,767 (95% Crl: $1,179; $4,822), consequently yielding a large ICER value of $192,618 per QALY gained. Uncertainty regarding the ICER was high at a willingness-to-pay threshold of $100,000 per QALY, as shown in Appendix 6 (Figure A1). Sensitivity AnalysisWe conducted 19 scenario analyses to examine parameter and structural model uncertainty and their effects on the robustness of our initial results. The ICER and incremental net benefit estimates for the scenarios are presented in Table 13, which presents cost–utility analysis results comparing each CBT strategy with usual care, and Table 14, which presents cost–utility analysis results comparing best-ranked strategies. Table 13:Sensitivity Scenario Analysis Results: CBT Strategies Versus Usual Carea
Table 14:Sensitivity Scenario Analysis Results: Best-Ranked Strategiesa
The results remained robust in all 19 scenarios comparing group or individual CBT provided by nonphysicians or group CBT provided by physicians with usual care (Table 13). We found that interpersonal therapy represents good value for money when compared with no treatment. In all analyses, psychological treatment was associated with more benefits. It was also often associated with increments in costs, unless the strategy was shown to be cost saving, in which case the cost of usual care was greater than the cost of psychotherapy. Therefore, the values of the ICERs kept the same rankings in all scenarios, with group CBT provided by nonphysicians being associated with the lowest estimates (ranging from cost-saving values to $16,763/QALY when only the costs of CBT treatment were analyzed). However, in 9 of 19 scenarios comparing individual CBT provided by physicians with usual care, the ICER was above $50,000 per QALY, suggesting that this strategy may not be optimal (in economic terms) for populations such as patients initially diagnosed with severe major depressive disorder (scenario 2; see Table 13) or patients likely to drop out of treatment (scenario 5; see Table 13), or if the utility associated with CBT were 10% lower (scenario 10; see Table 13). Further, the ICER was over $69,000 per QALY if the number of CBT sessions were high (e.g., 20) (scenario 11; see Table 13). Interestingly, if the efficacy of CBT were 25% lower than that reported in the literature, the ICER was greater than $52,000 per QALY (scenario 4; see Table 13). Finally, when the downstream costs of major depressive disorder treatment were not taken into account (i.e., those associated with the course of CBT therapy, the initial assessment by a psychiatrist or psychologist, and follow-ups by a general practitioner), and only the costs of CBT treatment were analyzed, the ICER for individual CBT provided by physicians versus usual care was over $56,000 per QALY (scenario 15; see Table 13). Our second set of probabilistic sensitivity analysis scenarios, shown in Table 14, compared the best-ranked strategies with each other. This analysis demonstrated robust cost-effectiveness findings in all but 2 scenarios. The first of these was the only scenario associated with an ICER less than $50,000 per QALY was one testing the duration of the model's time horizon. After a very long follow-up time of at least 20 years, individual CBT provided by a physician was found to be a better option than group therapy provided by a nonphysician (scenario 19; see Table 14). The second was the scenario that examined CBT provided by a general practitioner (instead of a psychiatrist). We found that the estimated costs of individual CBT provided by general practitioners were somewhat lower than those for individual therapy provided by nonphysicians but that the benefits of the two were equal. Thus, we found that individual CBT provided by general practitioners was comparable to group therapy provided by nonphysicians but that the ICER was still much higher than $100,000 per QALY ($131,431/QALY, scenario 12; see Table 14). In all other scenarios, we found that a decision-maker would always need to pay more than $100,000 per QALY gained if they were to choose individual CBT over group CBT. In these analyses, the ICERs ranged from $106,000 per QALY to more than $306,000 per QALY (scenario 11; see Table 14). DiscussionOur model-based cost-effectiveness analysis showed that both individual and group CBT provided by any regulated health care professional (i.e., physician or nonphysician) for the management of major depressive disorder and/or generalized anxiety disorder represent good value for money compared with usual care. All CBT strategies were associated with ICERs less than $50,000 per QALY gained. CBT provided as group therapy by nonphysicians was associated with the lowest ICER of $3,715 per QALY gained, whereas CBT provided as group therapy by psychiatrists was associated with the highest ICER of $43,443 per QALY gained. The probability of group CBT strategies being cost-effective is over 92% at a willingness-to-pay threshold of $50,000 per QALY, and is over 80% for any CBT strategy at a willingness-to-pay threshold of $100,000 per QALY. Our findings remained robust in all scenario analyses, with group CBT provided by nonphysicians being associated with the lowest ICER estimates (ranging from cost-saving values to $16,763 per QALY when we analyzed only the costs of CBT treatment). Our results, which are applicable to the context of Ontario's health system, align with the findings of various cost-effectiveness analyses, described within our systematic review of the economic literature. An additional strength of our economic modeling study is that we examined the incremental cost-effectiveness of structured in-person psychotherapy versus usual care in the management of adults with first and recurrent episodes of mild or moderate to severe depression and/or anxiety. With respect to changes in the probabilities of important health outcomes over a 5-year follow-up, we found that individual and group CBT increased life expectancy (0.5–1 day), significantly decreased the number of recurrent major depressive episodes, and significantly reduced the probability of hospitalization (1.4%–1.6%). Consequently, there is substantial potential for CBT to reduce the long-term negative effects of recurrent and treatment-resistant (complex) depression. Interestingly, we found that compared with group CBT provided by nonphysicians, individual CBT provided by nonphysicians was found not to be cost-effective at a willingness-to-pay threshold of $100,000 per QALY. This CBT strategy was associated with extremely high ICERs in both the base case and scenario analyses. However, this finding should be applied to clinical practice with caution for at least three reasons:
Future research and guidelines should address patient preferences regarding CBT strategy. Given the differences in the costs of various strategies, future guidelines should suggest situations when a particular CBT option may be preferred over another to enable the rational use and better allocation of scarce health care resources. Although our comprehensive economic analysis used the individual-level Markov modelling approach to accurately represent the clinical course of major depressive disorder, it is associated with several limitations. First, we assumed a limited number of recurrent major depressive episodes before a patient would enter the complex depression health state, and we simplified the patient journey through several clinical pathways. Thus, we did not fully address the complexity of secondary psychiatric care, nor did we model the use of CBT in complex depression or the effectiveness of various additional types of treatment for treatment-resistant depression. Our results remained robust in all scenarios, including those that addressed patient dropout or less frequent follow-up visits, but the benefits of psychotherapies still might be underestimated. Second, we focused on addressing whether psychotherapy represents good value for money and thus did not examine the cost-effectiveness of collaborative team care or stepped care; this decision problem relates to implementation issues, which ought to be carefully tailored to patient needs. Next, based on the limitations of the existing literature, we assumed that the efficacy of CBT is the same for every new episode and that there is no difference in the effectiveness of CBT delivery among the various types of regulated providers of psychotherapy services. We also demonstrated the cost-effectiveness of CBT for the management of generalized anxiety disorder and interpersonal therapy for the management of major depressive disorder. These result agree with clinical practice, as CBT is recognized as an effective therapy for generalized anxiety disorder, whereas both CBT and interpersonal therapy are used in the management of major depressive disorder. Therefore, our study is generalizable to the population of patients with major depressive disorder and those with generalized anxiety disorder, with either new or manageable recurrent disease. However, our evaluation focused only on populations with major depressive disorder and generalized anxiety disorder. Future research to evaluate psychological treatments for complex forms of depression or other disabling mental health disorders (including all types of anxiety disorders) is needed. ConclusionsOur economic evaluation suggests that, compared with usual care, structured forms of individual or group psychotherapy (i.e., CBT or interpersonal therapy) delivered by both physicians and nonphysicians represent good value for money. BUDGET IMPACT ANALYSISWe conducted a budget impact analysis from the perspective of the Ontario Ministry of Health and Long-Term Care to estimate the cost burden over the next 5 years of providing access to individual or group psychological therapies by regulated therapists to adults diagnosed with major depressive disorder or generalized anxiety disorder. All costs are reported in 2017 Canadian dollars.97 Reporting and analysis were done and are in accordance with the 2012 International Society for Pharmacoeconomics and Outcomes Research good-practice guidelines for budget impact analysis.141 Research Questions
MethodsWe used outputs from our cost-effectiveness analysis model to estimate budget impact. Therefore, our budget impact analysis accounted for heterogeneity in the patient populations with respect to age and disease severity, differences in clinical pathways, disease prognosis, and consequent differences in resource use and costs. Target PopulationOur study population included newly diagnosed adult outpatients aged 18 years or older with a primary diagnosis of mild or moderate to severe major depressive disorder and/or generalized anxiety disorder as defined by the DSM-5 criteria.71,84–87 We based overall estimates of the incidence of primary major depressive disorder on data from the 2012 Canadian Community Health Survey and the 2010 National Population Health Survey.85,142,143 Approximately 30% of patients with major depressive disorder have treatment-resistant depression127 and were thus excluded from our target population. Canadian estimates of the incidence of major depressive disorder were 2.9% in 2 years and 5.7% in 4 years.85,143 Therefore, we used an annual incidence rate of 1.8%144,145 to estimate the target population of adults with major depressive disorder. According to the newest census estimates, there are 11,763,400 adults in Ontario; of these, 148,219 are assumed to be newly diagnosed with major depressive disorder as of 2016 (Table 15).146 In a separate scenario analysis, we examined the generalized anxiety disorder population only. Table 15:Expected Number of Newly Diagnosed Patients With Major Depressive Disorder Eligible for CBT in Ontario, 2017 to 2021
UptakeIn the base case, we assumed that access to psychotherapy would increase gradually over 5 years from 0% to 100% (an increase of 20% each year). We based the assumption of no access to psychotherapy at baseline on expert consultation and literature indicating that a very small percentage of family health teams currently provide structured CBT.118,147 Thus, in Table 15, we present the expected number of patients that would gradually access CBT services in the next 5 years, from 2017 to 2021. For our budgetary impact calculations, it was important to estimate the cohort of patients at risk. Based on our model outputs, we estimated the percentage of patients who survived at the beginning of each year (Table 16). Table 16:Probability of Patients Surviving at the Beginning of Each Year Year
Based on data presented in Tables 15 and 16, we estimated the cohort of patients who will be at risk in the next 5 years. In Table 17, we provide an example of these calculations for the scenario comparing CBT provided as a group therapy by nonphysicians with usual care. Table 17:Expected Number of Patients at Risk: Group CBT Provided by Nonphysicians Versus Usual Care
For each scenario (Table 18 and Appendices 7–9), we estimated the total number of patients at risk over the next 5 years; these numbers were then used to estimate the net budget impact of publicly funding CBT over the next 5 years. Table 18:Expected Number of Patients at Risk in Ontario, 2017 to 2021
Canadian CostsBased on the model estimates of direct medical costs (derived from deterministic cost–utility analyses without discounting), we calculated the average annual costs per patient from year 1 to year 5 (Table 19). Table 19:Average Costs per Patient Each Year Post-Diagnosis of Major Depressive Disordera
We further adjusted the estimates of average costs per patient for those remaining in the analysis (i.e., survivors) over the next 5 years, using the data presented in Tables 16 and 19, which are the final average cost estimates for patients at risk. We used these data to calculate the net budgetary impact for each scenario (in 2017 Canadian dollars). Analysis 1: Base Case Budget Impact Analysis and Sensitivity Budget Impact AnalysesTo address all possible scenarios in Ontario, we conducted the following budgetary impact analyses:
Analysis 2: Number of Therapists NeededOur second objective was to determine the number of health care professionals needed to support timely access to CBT in Ontario. Table 21 presents our estimation of expected numbers of patients who could be treated with either group or individual CBT in one calendar year per full-time therapist. Table 21:Expected Number of Patients per Year for Group or Individual CBT per FTE
Based on the outputs of our model, we estimated an average number of major depressive episodes per patient for those remaining in the analysis (i.e., survivors) (Table 22). Table 22:Average Number of Major Depressive Episodes per Patient Each Year Post-Diagnosis of Major Depressive Disorder, Patients at Risk
Table 23 shows estimates of the number of CBT courses needed for patients with newly diagnosed or recurrent disease (years 1 to 5), after adjusting for the number of major depressive episodes (see Table 22) and given a gradual uptake of CBT in the province. Table 23:Expected Number of CBT Courses Needed (New and Recurrent Major Depressive Episodes), Ontario, 2017 to 2021
ResultsAnalysis 1: Base Case Budget Impact AnalysisTable 24 presents calculations of the net budget impact in detail, using the data presented in Tables 17 and 20 for the scenario comparing group CBT provided by nonphysicians with usual care. This strategy was associated with the lowest ICER in our cost–utility analysis, representing an optimal option for providing access to CBT in Ontario for patients with a primary diagnosis of major depressive disorder (alone or combined with generalized anxiety disorder). Adopting this CBT strategy at a 20% uptake rate would lead to an increase in costs of about $11 million in 2017 and about $68 million in 2021, when full access is achieved. Table 20:Average Costs per Patient Each Year Post-Diagnosis of Major Depressive Disorder, Patients at Risk
Table 24:Net Budget Impact of Adopting Group CBT Provided by Nonphysicians in Ontario: 2017 to 2021
The net budget impact of the other 3 CBT strategies ranges from $20 million (group CBT provided by physicians) to $42 million (individual CBT provided by physicians) in 2017, and from $199 million (group CBT provided by physicians) to $529 million in 2021 (individual CBT provided by physicians) (Table 25). Table 25:Results of Budget Impact Analysis: Other CBT Strategies Versus Usual Care
Analysis 1: Sensitivity Budget Impact AnalysesScenario 1: Generalized Anxiety Disorder PopulationWe conducted the first scenario analysis for the population with generalized anxiety disorder only, treated with 10 sessions of CBT. The evidence for the incidence of generalized anxiety disorder in Canada and worldwide is scarce148,149; approximately 2.5% of Ontarians are reported to have generalized anxiety disorder.72 After accounting for adults who have both major depressive disorder and generalized anxiety disorder (50%), we arrived at a target population estimate of 147,042 people with generalized anxiety disorder. The annual average costs per patient for the population at risk are presented in Appendix 7. Table 26 presents final budget impact estimates. Table 26:Results of Budget Impact Analysis: CBT Strategies Versus Usual Care for Generalized Anxiety Disorder
The net budget impact associated with CBT strategies for the generalized anxiety disorder population is also large. It ranges from $10 million (group CBT provided by nonphysicians) to $37 million (individual CBT provided by physicians) in 2017, and from $52 million (group CBT provided by nonphysicians) to $410 million in 2021 (individual CBT provided by physicians) (see Table 26). Scenario 2: Heterogeneity of the Major Depressive Disorder Population: Moderate to Severe Major Depressive DisorderThe second scenario addressed the heterogeneity of the major depressive disorder population by assessing the budget impact for patients with a more severe form of major depressive disorder. This population is prone to a higher rate of episode recurrence and worse health outcomes. Based on the literature, approximately 32% of patients with major depressive disorder are initially diagnosed with moderate to severe major depressive disorder (n = 47,430). Appendix 8 provides calculations of annual average costs per patient for the population at risk. Table 27 presents final budget impact analysis results. Table 27:Results of Budget Impact Analysis: CBT Strategies Versus Usual Care for Moderate to Severe Major Depressive Disorder
Owing to a smaller target population, the net budget impact for this scenario is much lower than for others. It ranges from $4 million (group CBT provided by nonphysicians) to $13 million (individual CBT provided by physicians) in 2017. In 2021, adopting any CBT strategy at an uptake rate of 100% would lead to an increase in costs ranging from $32 million (group CBT provided by nonphysicians) to $175 million (individual CBT provided by physicians). Scenario 3: Costs Associated With CBT Treatment OnlyThe third scenario estimated the budget impact if only the costs associated with CBT treatment are included (i.e., the costs of the initial assessment, providing 14 sessions of CBT, and follow-ups by a psychiatrist and general practitioner). This analysis included all adults with newly diagnosed major depressive disorder (n = 148,219). Appendix 9 presents calculations of the annual average costs per patient for the population at risk. Table 28 presents final budgetary impact results. Table 28:Results of Budget Impact Analysis: Costs of CBT Treatment Only
Overall, the results from the sensitivity analyses indicate the ranges of investment over the next 5 years for the Ontario Ministry of Health and Long-Term Care if the Ministry were to adopt any of the compared CBT strategies. Although all CBT strategies represented good value for money in the primary economic evaluations, they are associated with large net budget impacts, ranging from $17 million to $48 million in the first year of adoption at an uptake rate of 20%. Adopting any CBT strategy at an uptake rate of 100% would cost the province an additional $182 million to $656 million, depending on the type of CBT (group vs. individual) and type of delivery (nonphysician vs. physician). Analysis 2: Estimating the Number of Therapists Needed in Ontario, 2017 to 2021Based on the expected number of patients who could be treated per full-time therapist annually with either group CBT (N = 708, Table 21) or individual CBT (N = 118, Table 21), and the expected number of CBT courses per year (Table 23), we calculated that 500 therapists would be needed to provide group CBT therapy for all potential patients with a primary diagnosis of major depressive disorder (alone or combined with general anxiety disorder) in Ontario in 2021 (Table 29). For individual CBT, 2,934 therapists would be needed to provide therapy for all potential patients in Ontario in 2021. Table 29:Expected Number of Therapists Needed to Provide Group and Individual CBT in Ontario, 2017 to 2021
Based on expert consultation, psychotherapy training may take about 8 months for professionals with Master's degrees. This consists of about 1,000 hours of client work, 100 hours of supervised work, and 50 hours of providing in-person psychotherapy, as regulated by the College of Registered Psychotherapists of Ontario. For psychologists with an undergraduate degree, training may take around 4,000 hours of supervised clinical practice (as regulated by the College of Psychologists of Ontario). Further, CBT therapists (of any regulated health profession) should be certified in CBT delivery by a national CBT credentialing body to ensure the quality of therapeutic delivery. According to estimates from the Ontario Psychological Association (personal communication) and the Ontario Society of Psychotherapists (personal communication), there are currently around 4,100 trained psychologists (50% employed in public practice) and around 270 trained psychotherapists providing psychological therapies in Ontario. DiscussionWe conducted a model-based budget impact analysis to examine the range of investment needed to enable full access to necessary structured psychological treatments for patients with major depressive disorder and/or generalized anxiety disorder. We used CBT as a representative type of structured psychotherapy, as it is the most researched form of psychological therapy and is also widely used in clinical practice. Our budget impact analysis found that the costs of adopting CBT are high, most likely owing to the large number of people suffering from major depressive disorder and generalized anxiety disorder. Adding CBT to usual care over the next 5 years would cost the province between $68 million and $529 million, depending on the type of treatment (group vs. individual) and type of provider (nonphysician vs. physician). Our analysis indicates that CBT provided as group therapy by any publicly funded, regulated therapist (i.e., a nonphysician) is the most affordable option for the province. However, individual CBT represents good value for money and should be available to those patients who are not engaging well with or adhering to group therapy. If individual CBT provided by nonphysicians were provided to a maximum of 20% of patients with major depressive disorder, the net budget impact would be about $28 million. Our analysis also shows that restricting CBT to patients with moderate to severe major depressive disorder may be a more affordable option. Assuming that 1 in 5 patients would have access to psychotherapy in 2017, the increase in costs would be $4 million for group CBT provided by nonphysicians or $13 million for individual CBT provided by physicians. At the end of 2021, if all potential patients were to have full access, the corresponding cost increases would range from $32 million to $175 million. To provide CBT to all potential patients with a primary diagnosis of major depressive disorder by 2021 in Ontario, around 500 therapists would be needed to deliver group therapy, and about 2,930 therapists would be needed to deliver individual therapy. It is important to recognize that any regulated health professional providing psychotherapy should be certified by a national credentialing body to ensure the quality of therapeutic delivery. Data from professional organizations and our analysis suggest that we may currently have an adequate number of regulated professionals who could potentially provide therapy in the first years of adoption. Therefore, implementation efforts would need to be focused on investments in infrastructure120 and the organization of outpatient psychological treatment care for adults with major depressive disorder and generalized anxiety disorder in Ontario. ConclusionsThe most affordable option for providing publicly funded structured psychotherapy to adults with major depressive disorder and/or generalized anxiety disorder is group psychotherapy delivered by regulated nonphysician therapists. Selective delivery of individual structured psychotherapy by regulated nonphysician therapists or physicians is recommended for those patients who would benefit most from it (i.e., those who are not engaging well with or adhering to group therapy). PATIENT, CAREGIVER, AND PUBLIC ENGAGEMENTObjectiveThe objective of this analysis was to explore the underlying values, needs, impacts, and preferences of those who have lived experience with major depressive disorder and generalized anxiety disorder and psychological treatments for these disorders. The treatment focus was cognitive behavioural therapy (CBT), interpersonal therapy, and supportive therapy. BackgroundPublic and patient engagement explores the lived experience of a person with a health condition, including the impact that the condition and its treatment has on the patient, as well as the patient's family or other caregivers, and on the patient's personal environment. Public and patient engagement increases awareness and builds appreciation for the needs, priorities, and preferences of the person at the centre of a treatment program. The insights gained through public and patient engagement provide an in-depth picture of lived experience through an intimate look at the values that underpin the experience. Lived experience is a unique source of evidence about the personal impact of a health condition and how that condition is managed, including what it is like to navigate the health care system with that condition, and how health technologies or interventions may or may not make a difference in people's lives. Information shared from lived experience can also identify gaps or limitations in published research (for example, outcome measures that do not reflect what is important to those with lived experience).150–152 Additionally, lived experience can provide information or perspectives on the ethical and social values implications of technologies and interventions. Mental health conditions can have a significant impact on the lives of people living with these conditions and their families. To understand the impact of these disorders on the quality of life of those living with them, we spoke with people and families of people with lived experience of these mental health conditions who also had experience with psychotherapy treatment. Understanding and appreciating the day-to-day functioning of people with major depressive disorder and generalized anxiety disorder and their experience with types of treatment, including psychotherapy, helps to contextualize the potential value of psychotherapy. MethodsEngagement PlanEngagement as a concept captures a range of efforts used to involve the public and patients in various domains and stages of health technology assessment decision-making.153 Rowe and Frewer outline three types of engagement: communication, consultation, and participation.154 Communication constitutes a one-way transfer of information from the sponsor to the individual, whereas participation involves the sponsor and individual collaborating through real-time dialogue. Consultation refers to the sponsor seeking out and obtaining information (e.g., through experiential input) from the public, patients, and caregivers affected by the technology or intervention in question.155 The engagement plan for this health technology assessment focused on consultation. Within this typology, the engagement design focused on interviews to elicit the lived experience of patients with major depressive disorder or generalized anxiety disorder and their families, as well as their experiences with accessing and using psychotherapy as a treatment option. The qualitative interview was selected as an appropriate methodology because it allowed us to explore the meaning of central themes in the lived experience of the participants. The main task in interviewing is to understand the meaning of what participants say.156 Interviews are particularly useful for getting the story behind a participant's experiences, which was the objective of this portion of the study. The sensitive nature of exploring quality of life for this topic is another factor supporting the use of interviews for this project. Recruitment of ParticipantsOur recruitment strategy for this project used an approach called purposive sampling to actively recruit people with direct lived experience.157–160 Patient, Caregiver, and Public Engagement staff contacted people with experience of psychotherapy and their families through a variety of partner organizations, health clinics, local and provincial mental health support associations, and foundations. Inclusion CriteriaWe sought to speak with people who had experienced treatment with psychotherapy, specifically CBT, interpersonal therapy, or supportive therapy, for the treatment of major depressive disorder and/or generalized anxiety disorder. Participants were not required to currently be receiving psychotherapy treatment, only to have had lived experience with it. We sought a broad geographic, cultural, and socioeconomic representation to elicit possible equity issues in accessing and receiving psychotherapy treatment. Exclusion CriteriaWe set no exclusion criteria. ParticipantsWe spoke with 20 people with a history of major depressive disorder and/or generalized anxiety disorder who had experienced psychotherapy as a form of treatment. Participants were all over 18 years of age and were recruited from locations across Ontario. Participants reported living in rural and remote locations, as well as urban centres. ApproachAt the beginning of the interview, we explained the purpose of the health technology assessment process (including the role and mandate of Health Quality Ontario and the Ontario Health Technology Advisory Committee), risks of participation, and protection of personal health information. We explained these attributes to participants orally and through a letter of information (Appendix 10) and obtained consent from participants prior to commencing the interview (Appendix 11). Interviews were recorded and transcribed. Interview questions focused on the impact of the lived condition on the participants' and their families' quality of life, experiences with other health interventions to manage and treat their mental health condition, experiences with psychotherapy, any barriers experienced to receiving treatment, and any perceived benefits or limitations of treatment. The interview guide is presented in Appendix 12. The interview were semi-structured, consisted of a series of open-ended questions, and lasted for approximately 30 to 90 minutes. Questions for the interview were based on a list developed by the Health Technology Assessment International Interest Group on Patient and Citizen Involvement in HTA to elicit lived experiences specific to the impact of a health technology or intervention.161 Data Extraction and AnalysisWe selected a modified version of a grounded theory methodology to analyze transcripts of participant interviews, because this methodology captures themes and allows elements of lived experience to be compared among participants. The inductive nature of grounded theory follows an iterative process of eliciting, documenting, and analyzing responses while simultaneously collecting and analyzing data using a constant comparative approach.162,163 Through this approach, staff coded transcripts and compared themes using the qualitative software program NVivo (QSR International, Doncaster, Victoria, Australia). NVivo allowed us to identify and interpret patterns in the interview data about the meaning and implications of living with major depressive disorder or generalized anxiety disorder from the patients' perspective of what is important in their daily lived experience, both before and after receiving psychotherapy treatment. ResultsLived Experience of Major Depressive Disorder and Generalized Anxiety DisorderSymptoms of depression or anxiety manifested in various ways and were associated with a myriad of causes, from childhood trauma, to events experienced as an adult (e.g., divorce, death of a family member, estrangement from family) or other psychological conditions. Many participants emphasized the unique and personal nature of their experiences and outcomes, stating that their views of mental health treatments such as psychotherapy may not apply to others. Despite these personal differences, participants did express some commonalities in their experiences. Participants consistently reported that their disorder had a significant negative impact on their lives and that this impact extended to all facets of their lives: social, emotional, and physical. Several participants spoke of the reduced quality of life caused by the impact of their mental health condition. Common examples were estrangement from friends and families, a reduced capacity to work, and a withdrawal from social events and connections:
Participants often spoke of their mental health issues beginning in adolescence or earlier, resulting in a negative impact that lasted for decades. Participants said that they associated their mental health condition with stigma and shame, whether manifested as an adult or adolescent:
Participants reported wanting to hide the challenges they were facing and hesitating to share their problems with others, even members of their own families. In some cases, participants had experienced physical or emotional trauma in childhood and felt that these experiences had caused their depression or anxiety. These participants said that seeking help for their complex mental health issues was especially challenging. Almost all participants spoke of the challenge of first overcoming the perceived stigma and shame to seek treatment. Often, this took years:
Other Types of Treatment for Major Depressive Disorder and Generalized Anxiety DisorderParticipants reported pharmacotherapy as the primary alternative or companion to psychotherapy to treat their mental health conditions. However, they often reported hesitation when first making the decision to receive treatment with medication, worried about potential side effects and the stigma associated with taking medication:
The effectiveness of pharmacotherapy in treating major depressive disorder or generalized anxiety disorder varied for the people we interviewed. While some found medication beneficial, others reported that medications were rarely helpful and expressed frustration at what they perceived as an over-reliance on pharmacotherapy in the health care system. These participants often traced their depression or anxiety to specific traumatic events in their past and felt that medication would not relieve the ultimate source of their mental health issues:
Those participants who did report finding medication helpful and effective often found its effect to be limited in terms of its ability to eliminate their disorder completely. They often mentioned needing to try many different medications before finding one, or a combination of medications, that was effective. In addition, most participants viewed pharmacotherapy as a complement to psychotherapy rather than an alternative, stating that the most effective treatment for their mental health conditions was a careful combination of both psychotherapy and pharmacotherapy. However, this balance was often difficult to establish quickly or reliably:
Owing to the personal and unique nature of mental health disorders, participants often reported accessing multiple therapies in an attempt to find one that was effective. This occurred over a number of years, as participants attempted different treatments provided by different health care professionals. However, because of the cost and access challenges associated with what were perceived as the more effective treatments, participants often continued to use these less effective treatments, which resulted in longer treatment periods and frustration with the health care system:
Barriers to Accessing PsychotherapyThe experience of constantly searching for effective and accessible treatment was a common one for the people we interviewed. Participants reported searching for treatments that balanced effectiveness with cost. And, owing to the interpersonal nature of psychotherapy treatment, participants reported feeling that its effectiveness was often dependent on the health care professional providing the therapy. Therefore, participants identified three main barriers to finding effective and sustainable psychotherapy care: cost, physical access to the right health care professional (which often necessitated excessive wait times), and lack of information about care options. CostFor a large number of people interviewed, the cost of psychotherapy was reported as a barrier to accessing the type and frequency of psychotherapy they felt was needed to effectively treat their condition. Participants were often forced to choose between effectiveness and cost in their treatment decisions, which resulted in a longer duration of their mental health condition and a negative impact on their quality of life:
Participants who were able to afford the mental health treatment of their choice by paying out of pocket still reported feeling anxious about the cost of treatment and grateful when sliding fee scales were occasionally offered by a mental health care provider. This anxiety can arise from paying for health care services that may not ultimately be effective, whether owing to the interpersonal dynamics between the patient and therapist or the type of therapy offered:
Physical Access to Appropriate Treatment ProvidersParticipants reported that physically being unable to access a desired type of treatment provider was a common barrier. This physical barrier could be geographical in nature or come in the form of long wait lists. Participants from northern Ontario spoke of the long distance and travel time needed to see their chosen treatment provider. People from urban areas frequently spoke of how fortunate they felt to have a larger number of options for mental health services, which may not be available elsewhere:
Participants from all parts of the province consistently lamented the long wait lists that prevented them from accessing mental health services they felt could be helpful. Long wait lists were a source of extreme frustration and often resulted in participants accessing what they felt was less effective treatment or remaining with a health care professional they did not feel was helping them:
Several patients reported using hospital emergency department services in an attempt to circumvent long wait lists and access mental health services more quickly:
Lack of Information About Care OptionsA number of people interviewed mentioned a lack of information as a barrier to accessing the treatment that would be most effective. Participants reported feeling overwhelmed by the complexities of accessing the health care system and the different types of treatment available for mental health conditions. The feeling of being overwhelmed was reported to be more acute if the person's depression or anxiety had begun as an adolescent:
Several participants reported frustration at knowing that help and information were available, whether online or elsewhere, but not knowing how or where to access them:
Psychotherapy for Major Depressive Disorder and Generalized Anxiety DisorderParticipants reported positive results from receiving psychotherapy treatment once they were able to access it, but they differed in terms of which type of psychotherapy they found most effective: CBT, interpersonal therapy, or supportive therapy. Participants also had differences of opinion regarding preferences for group therapy versus individual psychotherapy. Some people found it more effective to speak in a group setting, whereas others found the most benefit from individual therapy sessions with a trusted health care professional. The differences in preference and perception of effectiveness of the different types of psychotherapy are likely a result of the personal and unique nature of a patient's experience of a mental health condition; methods that are most effective for one person may not be effective for another. The people we interviewed expressed this sentiment, acknowledging that their experiences, values, and perceptions of psychotherapy would not necessarily apply to others:
When speaking of the benefits of psychotherapy, many participants expressed relief at finding someone trusted in whom to confide and with whom share their emotional burden. This was especially true when a person had spent a great deal of time and money before finding a treatment provider with whom they could form this trusting relationship:
Other participants saw the benefit of psychotherapy in terms of the tools they learned to help them deal with their depression or anxiety, which allowed them to gain a sense of independence and self-reliance:
Finally, some participants who traced their depression or anxiety to traumatic childhood events felt that psychotherapy helped them to discuss and examine those events in a healthy way. Speaking of these events with a trusted treatment provider allowed a degree of relief and unburdening, which patients reported as being extremely beneficial:
A large number of the people we interviewed reflected on the time they had spent searching for treatment before finding effective psychotherapy. They lamented this as time wasted and expressed great frustration at the years needlessly spent living with depression or anxiety before finding effective psychotherapy:
DiscussionThe people we interviewed consistently reported on the negative impact that major depressive disorder and generalized anxiety disorder had on their quality of life. While the causes of the participants' disorders varied, participants expressed a similar desperate desire to find effective treatment for their conditions. They reported that after overcoming the perceived stigma and shame of their mental health issues, which itself was a lengthy process, they faced a long journey to obtain effective and sustainable treatment, whether psychotherapy, pharmacotherapy, or both. Owing to the personal and unique nature of each person's experience of a mental health issue, the participants' treatment journeys and the perceived benefits of treatment varied. Participants also differed in their views of the effectiveness of different types of psychotherapy (i.e., CBT, interpersonal therapy, and supportive therapy) and their preference for group versus individual therapy. However, all participants agreed that ultimately receiving their preferred type of psychotherapy benefited them in dealing with their depression or anxiety. Participants commonly experienced obstacles before finding successful treatment. These obstacles were often associated with access to the mental health treatment providers and treatments of their choice. Participants also reported experiencing a number of equity issues when trying to obtain psychotherapy services, including barriers associated with cost, geography, and access to information about different care options. ConclusionsThe people we spoke with who had lived experience of major depressive disorder or generalized anxiety disorder reported positive experiences with psychotherapy. However, they also reported experiencing a large number of barriers that prevented them from finding effective psychotherapy in a timely manner. Participants reported wanting more freedom to choose the type of psychotherapy they received. Too often, they felt they were forced to balance effectiveness and cost in their mental health treatment, which they felt resulted in having to rely on less effective treatment and increased time spent suffering from their condition. AcknowledgmentsThe medical editor was Kara Stahl. Others involved in the development and production of this report were Harrison Heft, Claude Soulodre, Ana Laing, Kellee Kaulback, Andrée Mitchell, Anil Thota, Vivian Ng, Nancy Sikich, and Irfan Dhalla. We are grateful to the following individuals for their expert advice in the preparation of this report: Nick Kates and Randi McCabe (McMaster University and St. Joseph's Healthcare Hamilton); Jan Kasperski (Ontario Psychological Association); Stephanie Carter, Judith Laposa, and Enza Mancuso (Centre for Addiction and Mental Health); Claire Watson (Ontario Society of Psychotherapists); Harindra Wijeysundera (University of Toronto); and David Tannenbaum (Mount Sinai Hospital, Toronto). The statements, conclusions, and views expressed in this report do not necessarily represent the views of the consulted experts. ABBREVIATIONS
GLOSSARY
APPENDICESAppendix 1: Literature Search StrategiesClinical Evidence SearchSearch date: October 27, 2016 Databases searched: Ovid MEDLINE, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, and NHS Economic Evaluation Database, and EBSCOhost CINAHL. Database: EBM Reviews – Cochrane Database of Systematic Reviews <2005 to October 26, 2016>, EBM Reviews – Database of Abstracts of Reviews of Effects <1st Quarter 2015>, EBM Reviews – Health Technology Assessment <3rd Quarter 2016>, EBM Reviews – NHS Economic Evaluation Database <1st Quarter 2015>, Embase <1980 to 2016 Week 43>, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) <1946 to Present>, PsycINFO <1967 to October Week 3 2016> Search Strategy:
EBSCOhost CINAHL
Grey LiteratureSearch date: October 31, 2016 Websites searched: HTA Database Canadian Repository, Alberta Health Technologies Decision Process reviews, Canadian Agency for Drugs and Technologies in Health (CADTH), Institut national d'excellence en santé et en services sociaux (INESSS), Institute of Health Economics (IHE), McGill University Health Centre Health Technology Assessment Unit, National Institute for Health and Care Excellence (NICE), Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Centers, Australian Government Medical Services Advisory Committee, Blue Cross Blue Shield Center for Clinical Effectiveness, Centers for Medicare & Medicaid Services Technology Assessments, Institute for Clinical and Economic Review, Ireland Health Information and Quality Authority Health Technology Assessments, Washington State Health Care Authority Health Technology Reviews, NHS PROSPERO International prospective register of systematic reviews Keywords used: cognitive; CBT; behavioural therapy; behavioral therapy; behavioral counselling; behavioral counseling; behavioural counselling; behavioural counseling; Interpersonal; IPT; supportive therapy; supportive counselling; supportive counseling; psychotherapy Results: 33 Economic Evidence SearchSearch date: October 28, 2016 Databases searched: Ovid MEDLINE, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane CENTRAL, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, and NHS Economic Evaluation Database, and EBSCOhost CINAHL Database: EBM Reviews – Cochrane Central Register of Controlled Trials <September 2016>, EBM Reviews – Cochrane Database of Systematic Reviews <2005 to October 26, 2016>, EBM Reviews – Database of Abstracts of Reviews of Effects <1st Quarter 2015>, EBM Reviews -Health Technology Assessment <3rd Quarter 2016>, EBM Reviews – NHS Economic Evaluation Database <1st Quarter 2015>, Embase <1980 to 2016 Week 43>, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) <1946 to Present>, PsycINFO <1967 to October Week 3 2016> Search Strategy:
EBSCOhost CINAHL
Grey LiteratureSearch date: October 31, 2016 Websites searched: HTA Database Canadian Repository, Alberta Health Technologies Decision Process reviews, Canadian Agency for Drugs and Technologies in Health (CADTH), Institut national d'excellence en santé et en services sociaux (INESSS), Institute of Health Economics (IHE), McGill University Health Centre Health Technology Assessment Unit, National Institute for Health and Care Excellence (NICE), Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Centers, Australian Government Medical Services Advisory Committee, Blue Cross Blue Shield Center for Clinical Effectiveness, Centers for Medicare & Medicaid Services Technology Assessments, Institute for Clinical and Economic Review, Ireland Health Information and Quality Authority Health Technology Assessments, Washington State Health Care Authority Health Technology Reviews, Tufts Cost-Effectiveness Analysis Registry, ClinicalTrials.gov Keywords used: cognitive; CBT; behavioural therapy; behavioral therapy; behavioral counselling; behavioral counseling; behavioural counselling; behavioural counseling; Interpersonal; IPT; supportive therapy; supportive counselling; supportive counseling; psychotherapy Results: 48 Appendix 2: Evidence Quality AssessmentTable A1:AMSTAR Scores of Included Systematic Reviews
Appendix 3: Characteristics of Systematic ReviewsTable A2:Characteristics of Systematic Reviews
Appendix 4: Results of Applicability Checklist for Studies Included in Economic Literature ReviewTable A3:Assessment of the Cost-Effectiveness of CBT or Interpersonal Therapy for Major Depressive Disorder and Generalized Anxiety Disorder
Appendix 5: Methodological Quality of Studies Included in Economic Literature ReviewTable A4:Assessment of the Cost-Effectiveness of CBT or Interpersonal Therapy for Major Depressive Disorder and Generalized Anxiety Disorder
Appendix 6: Incremental Cost-Effectiveness Scatter Plot: Individual CBT Provided by Nonphysicians Versus Group CBT Provided by NonphysiciansFigure A1:Scatter Plots of 1,000 Simulated Pairs of Incremental Costs and Effects in the Cost-Effectiveness Plane: Individual CBT Provided by Nonphysicians Versus Group CBT Provided by Nonphysicians Abbreviations: CBT, cognitive behavioural therapy; ICER, incremental cost-effectiveness ratio; WTP, willingness-to-pay threshold. All costs are in 2017 Canadian dollars and discounted at 1.5%. Effectiveness is expressed in quality-adjusted life-years (QALYs). Negative QALYs indicate that the individual CBT strategy was associated with worse quality-adjusted survival, and negative costs indicate that the individual CBT strategy saved money relative to the group CBT strategy. The diagonal line indicates a willingness-to-pay threshold of $100,000 per QALY. The incremental cost-effectiveness ratio ($192,618/QALY gained) is the slope of a straight line from the origin that passes through the (0.01 QALY, $2,767) coordinate. A 95% confidence ellipse covers 95% of the estimated joint density and was used to represent uncertainty around the incremental cost-effectiveness ratio estimated in the probabilistic sensitivity analysis. Appendix 7: Budget Impact Analysis—Scenario 1: Generalized Anxiety Disorder Population OnlyTable A5:Generalized Anxiety Disorder Population Scenario—Expected Number of Patients at Risk after Adopting CBT in Ontario, 2017 to 2021
Table A6:Generalized Anxiety Disorder Population Scenario—Average Costs per Patient Each Year Post-Diagnosis, Patients at Risk, Ontario, 2017 to 2021
Appendix 8: Budget Impact Analysis—Scenario 2: Moderate to Severe Major Depressive Disorder or Generalized Anxiety DisorderTable A7:Moderate to Severe Major Depressive Disorder Scenario—Expected Number of Patients at Risk After Adopting CBT in Ontario, 2017 to 2021
Table A8:Moderate to Severe Major Depressive Disorder Scenario—Average Costs per Patient Each Year Post-Diagnosis, Patients at Risk, Ontario, 2017 to 2021
Appendix 9: Budget Impact Analysis—Scenario 3: Costs Associated With CBTTable A9:CBT Treatment Costs Scenario—Expected Number of Patients at Risk After Adopting CBT in Ontario, 2017 to 2021
Table A10:CBT Treatment Costs Scenario—Average Costs per Patient Each Year Post-Diagnosis of Major Depressive Disorder, Patients at Risk, Ontario, 2017 to 2021
Appendix 10: Letter of InformationLETTER OF INFORMATIONSUMMARY:Health Quality Ontario (HQO) is conducting a formal assessment of Psychotherapy treatments for adult patients with Major Depressive Disorder and/or Generalized Anxiety Disorder, to better understand how these treatment options should be funded by the healthcare system. An important part of this assessment involves speaking to patients and families of those who suffer (or may have suffered) from these disorders, who may or may not have used psychotherapy for treatment. Our goal is to illuminate the lived-experience of patients and families who have experienced Major Depressive Disorder and/or Generalized Anxiety Disorder, and the context around psychotherapy treatment. WHAT DO YOU NEED FROM ME?
WHY DO YOU NEED THIS INFORMATION?Health Quality Ontario (HQO) is conducting a Health Technology Assessment of the effectiveness and safety of cognitive behavioural therapy, interpersonal therapy, and supportive therapy for adult patients with major depressive disorder and/or generalized anxiety disorder. As part of HQO's core function to promote health care supported by the best evidence available, established scientific methods are used to analyze the evidence for a wide range of health interventions, including diagnostic tests, medical devices, interventional and surgical procedures, health care programs and models of care. These analyses may be informed and complemented by input from a range of individuals, including patients and clinical experts, and serve as the basis recommendations about whether health care interventions should be publicly funded or not. The perspective that you share will be useful to help provide context to the day-to-day realities of patients dealing with mental health issues and the decisions they face in terms of therapies. The ultimate goal of the project is to provide recommendations to the Ontario Health Technology Assessment Committee who advises the Ontario Ministry of Health and Long-term Care on the appropriateness of funding. WHAT YOUR PARTICIPATION INVOLVESIf you agree to enroll, you will be asked to participate in an interview conducted by HQO staff. The interview will likely last 20–40 minutes. The session will be conducted in a private location and will be audio-taped. The interviewer will ask you questions about your lived experience with major depressive disorder and/or generalized anxiety disorder and your perspectives of psychotherapy treatment in Ontario. Participation is voluntary. You may refuse to participate, refuse to answer any questions or withdraw before your interview. Withdrawal will in no way affect care you receive. CONFIDENTIALITYAll information collected for the review will be kept confidential and privacy will be protected except as required by law. The results of this review will be published, however no identifying information will be released or published. Any records containing information from your interview will be stored securely. RISKS TO PARTICIPATION:There are no known physical risks to participating. Some participants may experience discomfort or anxiety after speaking about their lived experience. If this is the case, please contact any staff. HEALTH QUALITY ONTARIO STAFF:Appendix 11: Consent and Release FormConsent and Release FormThis form is to be read and completed in accordance with the following instructions before it can be signed.
Appendix 12: Interview GuideInterview for Psychotherapy HTAIntroExplain HQO purpose, HTA process, and purpose of interview History of mental health condition (MDD or GAD) (general only) Lived- ExperienceDay-to-day routine What is the impact of mental health condition on quality of life? What is the impact on family? TherapiesExperience with other therapies and mental health services Decision-making in choosing therapies? Was it difficult to weigh up potential benefits and risks when deciding on which therapies to go with? Availability of information surrounding mental health services – enough? Technology in mental health services. Pharmacotherapy Barriers to accessing therapies, including psychotherapy? PsychotherapyExperience with Psychotherapy – types, group v individual Expectations, barriers, benefits/drawbacks Mental health services in Ontario – biggest challenge? Contrast emotion (anxiety, worry) vs logic? As this applies to risk and side-effects? Author contributionsThis report was developed by a multidisciplinary team from Health Quality Ontario. The lead clinical epidemiologist was Kristen McMartin, the lead health economist was Olga Gajic-Veljanoski, the public and patient engagement specialist was David Wells, and the medical librarians were Caroline Higgins and Melissa Walter. KEY MESSAGESPeople with major depressive disorder experience depressed mood and loss of interest or pleasure in activities. People with generalized anxiety disorder experience persistent, excessive, and difficult-to-control worry. Often, people experience both disorders at the same time. Major depressive disorder and generalized anxiety disorder cause many symptoms that negatively affect work, education, and social interactions. Treatments for these disorders consist of pharmacological interventions (medications) and psychological interventions (talk therapies). Three commonly used psychological interventions for major depressive disorder and generalized anxiety disorder are cognitive behavioural therapy (CBT), interpersonal therapy, and supportive therapy. The objectives of this report were to assess the effectiveness and safety of CBT, interpersonal therapy, and supportive therapy for the treatment of adults with major depressive disorder and/or generalized anxiety disorder. We also assessed the cost-effectiveness of structured psychotherapy (CBT or interpersonal therapy) and calculated the budget impact of publicly funding structured psychotherapy. We then interviewed people with major depressive disorder and/or generalized anxiety disorder to learn about their experiences of these disorders and with different types of therapy. Compared with usual care, treatment with CBT, interpersonal therapy, or supportive therapy has been found to reduce depression symptoms and increase response or recovery posttreatment. In people with generalized anxiety disorder, treatment with CBT has been found to reduce symptoms of anxiety, improve outcomes, and improve ratings of quality of life. Compared with usual care, treatment with structured psychotherapy provided by physicians or nonphysicians, delivered as individual or group in-person therapy, represents good value for money. The most affordable option is structured group psychotherapy provided by nonphysicians, with the selective use of individual psychotherapy provided by nonphysicians or physicians for those who would benefit most from it. People with major depressive disorder and/or generalized anxiety disorder reported positive experiences with psychotherapy but also a large number of barriers that prevented them from finding effective psychotherapy in a timely manner. People with whom we spoke reported wanting more freedom to choose the type of psychotherapy they received, than they are currently able to access. Contributor InformationHealth Quality Ontario : About Health Quality OntarioHealth Quality Ontario is the provincial advisor on the quality of health care. We are motivated by a single-minded purpose: Better health for all Ontarians. Who We AreWe are a scientifically rigorous group with diverse areas of expertise. We strive for complete objectivity, and look at things from a vantage point that allows us to see the forest and the trees. We work in partnership with health care providers and organizations across the system, and engage with patients themselves, to help initiate substantial and sustainable change to the province's complex health system. What We DoWe define the meaning of quality as it pertains to health care, and provide strategic advice so all the parts of the system can improve. We also analyze virtually all aspects of Ontario's health care. This includes looking at the overall health of Ontarians, how well different areas of the system are working together, and most importantly, patient experience. We then produce comprehensive, objective reports based on data, facts and the voice of patients, caregivers and those who work each day in the health system. As well, we make recommendations on how to improve care using the best evidence. Finally, we support large scale quality improvements by working with our partners to facilitate ways for health care providers to learn from each other and share innovative approaches. Why It MattersWe recognize that, as a system, we have much to be proud of, but also that it often falls short of being the best it can be. Plus certain vulnerable segments of the population are not receiving acceptable levels of attention. Our intent at Health Quality Ontario is to continuously improve the quality of health care in this province regardless of who you are or where you live. 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[Google Scholar] Articles from Ontario Health Technology Assessment Series are provided here courtesy of Ontario Health What does the outcome of psychotherapy depend on?This viewpoint was more recently confirmed by Strupp (2001), who showed that the outcome of a psychotherapeutic process is often influenced by so-called non-specific factors, namely, the personal characteristics of the therapist and the positive feelings that arise in the patient – feelings which can lead to the ...
What is the standard duration of therapy?If you're going for individual counseling, then your session will last approximately 50-55 minutes. This 50-55 minutes is referred to as a "therapeutic hour." This is standard practice, although some clinicians will offer 45-minute sessions or 60-minute sessions.
What is the clinical definition of psychotherapy?Overview. Psychotherapy is a general term for treating mental health problems by talking with a psychiatrist, psychologist or other mental health provider. During psychotherapy, you learn about your condition and your moods, feelings, thoughts and behaviors.
What is the best source of evidence for the effectiveness of psychotherapy?Many studies, reviews, analyses, and trials have shown the efficacy of psychotherapy, demonstrating positive, enduring outcomes from both short-term and long-term intervention. In healthcare science, meta-analysis is generally considered the best way of assessing large bodies of evidence.
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