Cost-effectiveness analyses of augmented cognitive behavioral therapy for pharmacotherapy-resistant depression at secondary mental health care settings.

AIM: Pharmacotherapy is the primary treatment strategy in major depression. However, two-thirds of patients remain depressed after the initial antidepressant treatment. Augmented cognitive behavioral therapy (CBT) for pharmacotherapy-resistant depression in primary mental health care settings proved effective and cost-effective. Although we reported the clinical effectiveness of augmented CBT in secondary mental health care, its cost-effectiveness has not been evaluated. Therefore, we aimed to compare the cost-effectiveness of augmented CBT adjunctive to treatment as usual (TAU) and TAU alone for pharmacotherapy-resistant depression at secondary mental health care settings. METHODS: We performed a cost-effectiveness analysis at 64 weeks, alongside a randomized controlled trial involving 80 patients who sought depression treatment at a university hospital and psychiatric hospital (one each). The cost-effectiveness was assessed by the incremental cost-effectiveness ratio (ICER) that compared the difference in costs and quality-adjusted life years, and other clinical scales, between the groups. RESULTS: The ICERs were JPY -15 278 322 and 2 026 865 for pharmacotherapy-resistant depression for all samples and those with moderate/severe symptoms at baseline, respectively. The acceptability curve demonstrates a 0.221 and 0.701 probability of the augmented CBT being cost-effective for all samples and moderate/severe depression, respectively, at the threshold of JPY 4.57 million (GBP 30 000). The sensitivity analysis supported the robustness of our results restricting for moderate/severe depression. CONCLUSION: Augmented CBT for pharmacotherapy-resistant depression is not cost-effective for all samples including mild depression. In contrast, it appeared to be cost-effective for the patients currently manifesting moderate/severe symptoms under secondary mental health care.

Cost-utility analysis of curative and maintenance repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant unipolar depression: a randomized controlled trial protocol.

BACKGROUND: Depression is a debilitating and costly disease for our society, especially in the case of treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy in treatment-resistant unipolar and non-psychotic depression. It can be applied according to two therapeutic strategies after an initial rTMS cure: a further rTMS cure can be performed at the first sign of relapse or recurrence, or systematic maintenance rTMS (M-rTMS) can be proposed. TMS adjuvant to treatment as usual (TAU) could improve long-term prognosis. However, no controlled study has yet compared the cost-effectiveness of these two additional rTMS therapeutic strategies versus TAU alone. METHODS/DESIGN: This paper focuses on the design of a health-economic, prospective, randomized, double-blind, multicenter study with three parallel arms carried out in France. This study assesses the cost-effectiveness of the adjunctive and maintenance low frequency rTMS on the right dorsolateral prefrontal cortex versus TAU alone. A total of 318 patients suffering from a current TRD will be enrolled. The primary endpoint is to investigate the incremental cost-effectiveness ratio (ICER) (ratio costs / quality-adjusted life-years [QALY] measured by the Euroqol Five Dimension Questionnaire) over 12 months in a population of patients assigned to one of three arms: systematic M-rTMS for responders (arm A); additional new rTMS cure in case of mood deterioration among responders (arm B); and a placebo arm (arm C) in which responders are allocated in two subgroups: sham systematic M-rTMS and supplementary rTMS course in case of mood deterioration. ICER and QALYs will be compared between arm A or B versus arm C. The secondary endpoints in each three arms will be: ICER at 24 months; the cost-utility ratio analysis at 12 and 24 months; 5-year budget impact analysis; and prognosis factors of rTMS. The following criteria will be compared between arm A or B and arm C: rates of responders; remission and disease-free survival; clinical evolution; tolerance; observance; treatment modifications; hospitalization; suicide attempts; work stoppage; marital / professional statues; and quality of life at 12 and 24 months. DISCUSSION: The purpose of our study is to check the cost-effectiveness of rTMS and we will discuss its economic impact over time. In the case of significant decrease in the depression costs and expenditures associated with a good long-term prognosis (sustained response and remission) and tolerance, rTMS could be considered as an efficient treatment within the armamentarium for resistant unipolar depression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03701724. Registered on 10 October 2018. Protocol Amendment Version 2.0 accepted on 29 June 2019.

The Effectiveness and Value of Esketamine for the Management of Treatment-Resistant Depression.

DISCLOSURES: Funding for this summary was contributed by the Laura and John Arnold Foundation, National Institute for Health Care Management, California Health Care Foundation, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Healthcare, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, AstraZeneca, Allergan, Alnylam, Biogen, Blue Shield of California, Cambia Health Services, CVS Caremark, Editas, Express Scripts, Genentech, GlaxoSmithKline, Harvard Pilgrim Health Care, Health Care Service Corporation, HealthPartners, HealthFirst, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinkrodt Pharmaceuticals, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Agboola, Fazioli, and Pearson are employed by ICER. Touchette reports grants from ICER during the course of this work and personal fees from Monument Analytics, unrelated to this work. Atlas has nothing to disclose.

Dissociating the Clinical Role and Economic Value of Intranasal Esketamine.

DISCLOSURES: No funding supported the writing of this commentary. The author has nothing to disclose.

The humanistic and economic burden of treatment-resistant depression in Europe: a cross-sectional study.

BACKGROUND: A patient is considered to suffer from treatment resistant depression (TRD) when consecutive treatment with two products of different pharmacological classes, used for a sufficient length of time at an adequate dose, fail to induce a clinically meaningful effect (inadequate response). The primary aim of the current study was to examine the humanistic and economic burden of TRD in five European countries, France, Germany, Italy, Spain and the United Kingdom, by comparing with non-treatment resistant depression (nTRD) and general population respondents. METHODS: The sample for this retrospective observational study was taken from the 2017 National Health and Wellness Survey conducted in five European countries. Demographic and patient characteristics were examined for TRD patients compared to respondents with nTRD and to the general population using chi-square tests or one-way analysis of variance for categorical or continuous variables, respectively. Generalized linear models were performed to examine group differences after adjusting these estimates for confounders. RESULTS: A total 52,060 survey respondents were examined, of which 2686 and 622 were considered to have non-treatment resistant and treatment-resistant depression, respectively. Relative to the general population, nTRD and TRD respondents reported significant decrements in health-related quality of life, including lower adjusted mental (- 12.1 vs. -18.1) and physical (- 2.5 vs. -5.4) component scores of the SF-12v2 and increased adjusted relative risk for work (2.2 vs. 2.7) and activity (1.9 vs. 2.5) impairment (all p < 0.001). Additionally, healthcare resource utilization was significantly higher for TRD patients more so than nTRD, compared to the general population, especially for healthcare professional visits (odds ratio nTRD = 5.4; TRD = 15.9, p < 0.001). CONCLUSIONS: In conclusion, TRD patients had significantly lower quality of life, greater work productivity and activity impairment, and increased healthcare resource utilization as compared with nTRD and general population. The study findings suggest an unmet need exists among TRD patients in Europe.

Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental.

BACKGROUND: Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. METHOD: Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. RESULTS: The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. CONCLUSION: The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Current and Emerging Treatments to Address Unmet Needs in MDD.

Most people who experience a depressive episode are greatly impaired by it. No one-size-fits-all therapy is available, and most patients require multiple treatment steps. Check out this CME activity to learn about current and emerging strategies for managing MDD.

Antipsychotic Prescriptions Among Adults With Major Depressive Disorder in Office-Based Outpatient Settings: National Trends From 2006 to 2015.

OBJECTIVE: A recent moderately long-term study found an antipsychotic to be more effective than an antidepressant as the next-step treatment of unresponsive major depressive disorder (MDD). It is thus timely to examine recent trends in the pharmacoepidemiology of antipsychotic treatment of MDD. METHODS: Data from the 2006-2015 National Ambulatory Medical Care Survey, nationally representative samples of office-based outpatient visits in adults with MDD (ICD-9-CM codes 296.20-296.26 and 296.30-296.36) (n = 4,044 unweighted), were used to estimate rates of antipsychotic prescribing over these 10 years. Multivariable logistic regression analysis identified demographic and clinical factors independently associated with antipsychotic use in MDD. RESULTS: Antipsychotic prescribing for MDD increased from 18.5% in 2006-2007 to 24.9% in 2008-2009 and then declined to 18.9% in 2014-2015. Visits with adults 75 years or older showed the greatest decline from 27.0% in 2006-2007 to 10.7% in 2014-2015 (OR for overall trend = 0.73; 95% CI, 0.56-0.95). The most commonly prescribed antipsychotic agents were aripiprazole, olanzapine, quetiapine, and risperidone. Antipsychotic prescription was associated with being black or Hispanic, having Medicare among adults under 65 years or Medicaid as a primary source of payment, and receiving mental health counseling, 3 or more concomitant medications, and diagnosis of cannabis use disorder (P < .01). CONCLUSIONS: Antipsychotics, prescribed for about one-fifth of adults with MDD, increased and then declined from 2006 to 2015, reflecting, first, FDA approval and then concern about adverse effects in the elderly. Future research should track evolving trends following the publication of evidence of greater long-term effectiveness of antipsychotic than antidepressant next-step therapy in adults with MDD.

Cost-Effectiveness of Repetitive Transcranial Magnetic Stimulation versus Antidepressant Therapy for Treatment-Resistant Depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) therapy is a clinically safe, noninvasive, nonsystemic treatment for major depressive disorder. OBJECTIVE: We evaluated the cost-effectiveness of rTMS versus pharmacotherapy for the treatment of patients with major depressive disorder who have failed at least two adequate courses of antidepressant medications. METHODS: A 3-year Markov microsimulation model with 2-monthly cycles was used to compare the costs and quality-adjusted life-years (QALYs) of rTMS and a mix of antidepressant medications (including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclics, noradrenergic and specific serotonergic antidepressants, and monoamine oxidase inhibitors). The model synthesized data sourced from published literature, national cost reports, and expert opinions. Incremental cost-utility ratios were calculated, and uncertainty of the results was assessed using univariate and multivariate probabilistic sensitivity analyses. RESULTS: Compared with pharmacotherapy, rTMS is a dominant/cost-effective alternative for patients with treatment-resistant depressive disorder. The model predicted that QALYs gained with rTMS were higher than those gained with antidepressant medications (1.25 vs. 1.18 QALYs) while costs were slightly less (AU $31,003 vs. AU $31,190). In the Australian context, at the willingness-to-pay threshold of AU $50,000 per QALY gain, the probability that rTMS was cost-effective was 73%. Sensitivity analyses confirmed the superiority of rTMS in terms of value for money compared with antidepressant medications. CONCLUSIONS: Although both pharmacotherapy and rTMS are clinically effective treatments for major depressive disorder, rTMS is shown to outperform antidepressants in terms of cost-effectiveness for patients who have failed at least two adequate courses of antidepressant medications.

Assessment of the Efficacy and Safety of BMS-820836 in Patients With Treatment-Resistant Major Depression: Results From 2 Randomized, Double-Blind Studies.

Two phase 2B, randomized, double-blind studies assessed the efficacy and safety of fixed or flexible dose of triple monoamine uptake inhibitor BMS-820836 in patients with treatment-resistant depression to demonstrate whether switching to BMS-820836 was superior to the continuation of standard antidepressant treatment. Patients with a history of inadequate response to 1 to 3 adequate trials of antidepressant therapies were prospectively treated with duloxetine 60 mg/d for 8 weeks (CN162-006) or duloxetine 60 mg/d or escitalopram 20 mg/d for 7 weeks (CN162-007). Inadequate responders were randomized to continue their prospective phase treatment or switch to flexible-dose (0.5-2 mg/d; CN162-006) or fixed-dose (0.25, 0.5, 1, or 2 mg/d; CN162-007) BMS-820836 for 6 weeks. The primary end point in both studies was mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from randomization to study end point. BMS-820836 flexible (0.5-2 mg/d) or fixed dose of 1 mg/d or greater showed efficacy similar to the continuation of antidepressant treatment, with no statistically significant or clinically meaningful differences. In the CN162-006 study, the adjusted mean (SE) change in MADRS total score was -8.7 (0.661) and -8.1 (0.656) for BMS-820836 and duloxetine, respectively (P = 0.526). In the CN162-007 study, the adjusted mean (SE) change in MADRS total score was -7.3 (0.830) and -6.6 (0.842) for BMS-820836 of 1 and 2 mg, respectively, and -6.9 (0.602) for the continuation group (P = 0.910). Thus, BMS-820836 was well tolerated, with no evidence of dose-dependent discontinuations due to adverse events, but it failed to demonstrate superiority to the continuation of an existing antidepressant in patients with treatment-resistant depression.