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Background: Major depressive disorder (MDD) represents a sizable economic burden in Spain. Pharmacogenetic (PGx) screening to guide the choice of antidepressant medication (ADM) in MDD patients yields higher response and remission rates, which could reduce both healthcare and indirect costs., Methods: We built a cost-effectiveness probabilistic Markov model with microsimulation using Tree Age Pro 2022, simulating a patient cohort from the SNHS starting ADM for MDD, and comparing PGx screening before starting ADM versus no screening (No PGx). We carried out a probabilistic sensitivity analysis using the Monte Carlo simulation with microsimulation, set for 1000 iterations and 1000 microsimulation trials, both from societal and healthcare provider perspectives, for a time horizon of 3 years., Results: From a societal perspective, the model estimated a mean cost of 3172.85€ and effectiveness of 2.64 quality-adjusted life years (QALYs) for the No PGx strategy, and a mean cost of 1687.02€ and effectiveness of 2.84 QALYs for the PGx strategy. The mean ICER was -7820.56 €/QALY. From a healthcare provider perspective (no indirect costs considered), the mean cost was 662.62€ for the No PGx strategy, and 446.60€ for the PGx strategy. The mean ICER was -1130.16 €/QALY., Limitations: The heterogeneity of input data from the literature, the need for assumptions of homogeneous distribution of variables and events across population and time, and the inherent limitations of cost-effectiveness analysis should be considered. The model omits combined therapies (ADMs with mood stabilizers, antipsychotics, cognitive behavioral therapy…)., Conclusions: PGx screening in MDD prior to ADM start is a dominant strategy in the SNHS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: F.A.-S. has been consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Aptatargets, Chemo, Cinfa, FAES, Farmalíder, Ferrer, GlaxoSmithKline, Galenicum, Gilead, Italfarmaco, Janssen-Cilag, Kern, Moderna, MSD, Normon, Novartis, Servier, Silver Pharma, Teva, and Zambon. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In low-income and middle-income countries, individuals with major depressive disorder often do not receive screening and treatment. We assessed effectiveness and cost-effectiveness of an integrated care model for treating major depressive disorder in Malawi, accounting for two sets of positive externalities: household benefits and improvements in comorbidities., Methods: In this stepped-wedge, cluster-randomised, controlled trial, 14 health facilities in Neno District, Malawi, introduced screening, diagnosis, and treatment for people with major depressive disorder, using a stepped-care model of group Problem Management Plus and antidepressant therapy. Adults (ie, aged ≥18 years) residing in facility catchment areas, newly diagnosed with major depressive disorder, and actively enrolled in an integrated chronic care clinic were eligible for inclusion. People identified with high suicidal risk or psychotic symptoms were excluded. Health facilities were categorised into two strata (ie, health centres or secondary hospitals) and randomly allocated to one of five trial sequences, with intervention initiation staggered across sequences in 3-month periods. Participants were masked to trial sequence, data collectors were masked to treatment assignment, and the chief statistician was masked to treatment assignment until analysis. Services were delivered by counsellors and clinical officers at integrated chronic care clinics, and assessments took place at 3-month intervals over 27 months. Primary outcomes were changes in depressive symptom severity (measured with the Patient Health Questionnaire-9 [PHQ-9]), current depressive episode (PHQ-9 score of >10), and functioning (measured with the WHO Disability Assessment Schedule 2.0) over the 27-month period. Longitudinal mixed-effects regression analyses assessed outcomes from an intention-to-treat perspective. The trial was registered with ClinicalTrials.gov (NCT04777006) and is completed., Findings: Between Sept 1, 2021, and April 28, 2022, we conducted 15 562 screenings, resulting in 506 (3%) adults identified with major depressive disorder and 487 (3%) enrolled (395 [81%] women and 92 [19%] men). Assignment to IC3D corresponded to a 2·60-point (95% CI -3·35 to -1·86; d -0·61) reduction in depressive symptoms and 1·69-point (-2·73 to -0·65; -0·27) improvement in functioning, reflecting a reduced odds of depression after treatment roll-out (adjusted odds ratio 0·62, 95% CI 0·51 to 0·74)., Interpretation: Integrated care for people with major depressive disorder and chronic health conditions is effective at reducing depressive symptoms, improving functioning, and reducing the odds of depression, and facilitates expansion of services through existing infrastructure., Funding: National Institute of Mental Health., Competing Interests: Declaration of interests RKM, OM, KM, MK, WK, TR, EBW, FM, LD, GR, SLS, KK, MU, VP, and GJW declare no competing interests. SIW declares receipt of an honorarium as a member of the Medical Research Council's Applied Global Health Research Board and payment as an associated editor of BMJ Quality & Safety. EC declares financial support from Partners In Health to attend the Conference on Public Health in Africa in 2023., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: Variations in US commercial health plan coverage policies affect how patients access medications. Plans may vary in treatment access criteria, line of therapy, and prescriber requirements. In this study, we examined coverage of esketamine hydrochloride (Spravato) for major depressive disorder (MDD) and treatment-resistant depression (TRD) to answer the following question: how do US commercial health plans cover esketamine, and how do they guide prompt patient access to the drug?, Methods: We used information from the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes coverage policies issued by 18 large commercial health plans in the United States. Esketamine coverage policies for MDD and TRD active in December 2022 were collated and analyzed. We compared coverage policies according to step therapy protocols, patient subgroup restrictions, and prescriber requirement criteria, evaluating patient access using the number of restrictions and proportion of plans including each criterion., Findings: Plans more often imposed step therapy requirements for access to esketamine for TRD than for MDD, with line of treatment of ≤9 steps for MDD compared with 1 to 5 steps for TRD. Plans also varied with respect to the therapies they required patients to first try and experience treatment failure before granting access to esketamine for both indications. Clinical coverage requirements varied in thresholds and rating scales used to assess severity of depressive symptoms., Implications: Plans vary in terms of line of therapy and clinical coverage requirements for access to esketamine. Variation in health plan coverage policies may result in inequitable access and added complexity for patients and clinicians navigating care, which may delay access to urgent treatment., Gov Identifiers: Not applicable., Competing Interests: Declaration of competing interest The authors have completed the disclosure of interest form at www.icmje.org and declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Many patients with major depressive disorder (MDD) do not achieve remission with their first antidepressant (AD), resulting in a high burden due to treatment failure. Vortioxetine is a valid treatment option for patients with MDD only partially responding to their first AD. Characterization of vortioxetine's potential benefits versus other approved treatments is important. Areas covered: The cost-effectiveness of vortioxetine, including cognitive outcomes, was modeled in comparison with levomilnacipran and vilazodone for patients switched to these medications after inadequate responses to a first AD. Expert opinion: Vortioxetine was associated with incremental quality-adjusted life-year (QALY) gains versus levomilnacipran (0.008) or vilazodone (0.009). Vortioxetine was dominant versus levomilnacipran and cost-effective versus vilazodone (incremental cost-effectiveness ratio [ICER],33,829 USD/QALY). In sensitivity analyses using residual cognitive dysfunction rates (vortioxetine, 49%; levomilnacipran, 58%, and vilazodone, 64%), incremental QALY gains for vortioxetine versus levomilnacipran (0.0085) or vilazodone (0.0109) were found. Vortioxetine remained dominant versus levomilnacipran and cost-effective versus vilazodone (ICER, 27,633 USD/QALY). ICER reduction was found with cognition outcomes inclusion. This model provides additional support for considering vortioxetine for patients requiring a switch of MDD treatments, although its conclusions are limited by the data available for inclusion. Additional research and real-world trials are needed to confirm the findings.

Objective: The economic burden of commercially insured patients in the United States with treatment-resistant depression and patients with non-treatment-resistant major depressive disorder was compared using data from the Optum Clinformatics™ claims database., Methods: Patients 18-63 years on antidepressant treatment between 1/1/13 and 9/30/13, who had no treatment claims for depression 6 months before the index date (first antidepressant dispensing), and who had a major depressive disorder or depression diagnosis within 30 days of the index date, were included. Treatment-resistant depression was defined as receiving 3 antidepressant regimens during 1 major depressive disorder episode. Patients with treatment-resistant depression were matched with patients with non-treatment-resistant major depressive disorder at a 1:4 ratio using propensity score matching. The study consisted of 1-year baseline (pre-index) and 2-year follow-up (post index) periods. Cost outcomes were compared using a generalized linear model., Results: 2,370 treatment-resistant depression and 9,289 non-treatment-resistant major depressive disorder patients were included. In year 1 of the follow-up period, compared with non-treatment-resistant major depressive disorder, patients with treatment-resistant depression had: more emergency department visits (odds ratio = 1.39, 95% confidence interval = 1.24-1.56); more inpatient hospitalizations (odds ratio = 1.73, 95% confidence interval = 1.46-2.05); longer hospital stays (mean difference vs non-treatment-resistant major depressive disorder = 2.86, 95% confidence interval = 0.86-4.86 days); and more total healthcare costs (mean difference vs non-treatment-resistant major depressive disorder = US$3,846, 95% confidence interval = $2,855-$4,928). These patterns remained consistent in year 2 of the follow-up period., Conclusion: Treatment-resistant depression was associated with higher healthcare resource utilization and costs versus non-treatment-resistant major depressive disorder in this commercially insured cohort of patients in the United States., Competing Interests: The authors have read the journal’s policy and have the following competing interests: GL, AD, GW, JS, KL, and QZ are employees of Janssen Research & Development, LLC and hold stock in the company. LZ was an employee of Janssen Research & Development, LLC, at the time this study took place and is currently an employee of Boehringer Ingelheim Pharmaceuticals, Inc. JR is in research collaboration with Janssen, AstraZeneca, AbbVie, and Pfizer, for which Karolinska Institutet has received grant support. JR has been a speaker for Eli Lilly and received unrestricted grant support from Schering-Plough. Wilson Joe, PhD, of MedErgy, provided editorial support for this manuscript. Editorial support was funded by Janssen Research & Development, LLC. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Background: Electroconvulsive therapy (ECT) technique is often changed after insufficient improvement, yet there has been little research on switching strategies., Objective: To document clinical outcome in ECT nonresponders who were received a second course using high dose, brief pulse, bifrontotemporal (HD BP BL) ECT, and compare relapse rates and cognitive effects relative to patients who received only one ECT course and as a function of the type of ECT first received., Methods: Patients were classified as receiving Weak, Strong, or HD BP BL ECT during three randomized trials at Columbia University. Nonresponders received HD BP BL ECT. In a separate multi-site trial, Optimization of ECT, patients were randomized to right unilateral or BL ECT and nonresponders also received further treatment with HD BP BL ECT., Results: Remission rates with a second course of HD BP BL ECT were high in ECT nonresponders, approximately 60% and 40% in the Columbia University and Optimization of ECT studies, respectively. Clinical outcome was independent of the type of ECT first received. A second course with HD BP BL ECT resulted in greater retrograde amnesia immediately, two months, and six months following ECT., Conclusions: In the largest samples of ECT nonresponders studied to date, a second course of ECT had marked antidepressant effects. Since the therapeutic effects were independent of the technique first administered, it is possible that many patients may benefit simply from longer courses of ECT. Randomized trials are needed to determine whether, when, and how to change treatment technique in ECT., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This study compared health care use and costs among patients with treatment-resistant versus treatment-responsive depression across Medicaid, Medicare, and commercial payers., Methods: A retrospective cohort study was conducted by using Truven Health Analytics' commercial (2006-2017; N=111,544), Medicaid (2007-2017; N=24,036), and Medicare supplemental (2006-2017; N=8,889) claims databases. Participants were adults with major depressive disorder who had received one or more antidepressant treatments. Treatment resistance was defined as failure of two or more antidepressant treatments of adequate dose and duration. Annual use (hospitalizations and outpatient and emergency department [ED] visits) and costs were compared across patients by treatment-resistant status in each payer population. Incremental burden of treatment-resistant depression was estimated with regression analyses. Monthly changes in costs during 1-year follow-up were assessed to understand differential cost trends by treatment-resistant status., Results: In the three payer populations, patients with treatment-resistant depression incurred higher health care utilization than those with treatment-responsive depression (hospitalization, odds ratios [ORs]=1.32-1.76; ED visits, ORs=1.38-1.45; outpatient visits, incident rate ratio=1.29-1.54; p<0.001 for all). Compared with those with treatment-responsive depression, those with treatment resistance incurred higher annual costs (from $4,093 to $8,054 higher; p<0.001). Patients with treatment-resistant depression had higher costs at baseline compared with patients with treatment-responsive depression and incurred higher costs each month throughout follow-up., Conclusions: Treatment-resistant depression imposes a significant health care burden on insurers. Treatment-resistant depression may exist and affect health care burden before a patient is identified as having treatment-resistant depression. Findings underscore the need for effective and timely treatment of treatment-resistant depression.

Background: The purpose of this study was to evaluate the cost-effectiveness of antidepressants vs active monitoring (AM) for patients with mild-moderate major depressive disorder., Methods: This was a 12-month observational prospective controlled trial. Adult patients with a new episode of major depression were invited to participate and assigned to AM or antidepressants according to General Practitioners' clinical judgment and experience. Patients were evaluated at baseline, and 6 and 12-month follow-up. Quality-adjusted life years (QALYs) gained were estimated and used to calculate incremental cost-utility ratios (ICUR) from the healthcare and government perspective. To minimize the bias resulting from non-randomization, a propensity score-based method was used., Results: At 6 and 12-month follow-up, ICUR was 2549 €/QALY and 6,142 €/QALY, respectively, in favor of antidepressants. At 6 months, for a willingness to pay (WTP) of 25,000 €/QALY, antidepressants had a probability of 0.89 (healthcare perspective) and 0.81 (government perspective) of being more cost-effective than AM. At 12 months, this probability was 0.86 (healthcare perspective) and 0.73 (government perspective)., Conclusions: Incremental cost-utility ratios favor pharmacological treatment as a first-line approach for patients with mild-moderate major depressive disorder. While our results should be interpreted with caution and further real world research is needed, clinical practice guidelines should consider antidepressant therapy for mild-moderate major depressive patients as an alternative to active monitoring in PC.

Objective: Rates and determinants of pharmacological and psychotherapy use were assessed after a major depressive disorder diagnosis., Methods: In a retrospective claims study that included 2007-2016 records from the IBM MarketScan research databases, use of pharmacotherapy and psychotherapy was tracked in a population of 24,579 patients with a diagnosis of major depressive disorder. Univariate and multiple variable analyses were used to identify determinants of antidepressant adherence (proportion of days covered ≥.8) and intensive psychotherapy at the beginning of treatment (at least four psychotherapy visits in the first 4 weeks after initiating psychotherapy)., Results: In the 12 months following a diagnosis of major depressive disorder, most individuals received pharmacotherapy or psychotherapy (94.7%), and unimodal therapy was more common (58.5%) than bimodal therapy (36.2%). When antidepressants were initiated (N=13,524), 41.7% and 32.0% of patients were adherent in the acute and continuation phases, respectively. Initial antidepressant dosages were outside guideline recommendations for 34.5% of patients prescribed these medications. When psychotherapy was initiated, the median number of visits in the year after a patient's diagnosis was seven. Most patients (54.7%) did not continue to receive either antidepressant or psychotherapy treatment after month 5 following their diagnosis. A shorter time from diagnosis to treatment and a lower percentage of treatment costs paid by the patient were associated with increased antidepressant adherence and intensive psychotherapy use., Conclusions: Findings indicate that treatment guideline recommendations are not followed for a large proportion of patients with major depressive disorder and that improvement is needed in multiple areas to enhance effective treatment.

Background: Recent clinical trials indicate that pharmacogenetic-guided treatment of major depressive disorder (MDD) results in higher treatment response rates by genetically matching patients to medications and avoiding a trial-and-error process., Objective: To evaluate the cost-effectiveness of a pharmacogenetic test (IDGx) that has demonstrated effectiveness compared with standard of care (SOC) medication management among patients with varied MDD severity., Methods: Data from a large prospective, randomized controlled trial of treatment-naive patients or patients with inadequately controlled MDD in general practice and psychiatric treatment settings were used to build a Markov state-transition probability model. Analyses were conducted from the societal perspective. Treatment response rates, mortality rates, direct and indirect medical costs, and utility inputs were derived from the reference study and published scientific literature. The cost of the pharmacogenetic test was $2,000. A 3% discount rate was used to discount costs and effects. Univariate one-way sensitivity analyses were performed to determine the effect of input parameters on net monetary benefit., Results: For moderate to severe MDD, the model estimated a cumulative effect over 3 years of 2.07 quality-adjusted life-years (QALYs) for the pharmacogenetic-guided treatment group and 1.97 QALYs for the SOC group, including a lower probability of death from suicide (0.328% and 0.351%, respectively). Total costs over 3 years were $44,697 (IDGx) and $47,295 (SOC). This difference includes a savings of $2,918 in direct medical costs and $1,680 in indirect costs. Results were more pronounced when only severely depressed patients were evaluated., Conclusions: Pharmacogenetic testing among moderate to severe MDD patients improved QALYs and resulted in cost savings. Sensitivity analyses supported the robust nature of the current findings of the dominant IDGx test to guide treatment., Disclosures: Funding for this analysis was provided by AltheaDx, which is the manufacturer of the IDgenetix test. AltheaDx personnel assisted in the study design, data collection, and review of the manuscript. Maciel and Garces are employed by AltheaDx. Groessl has received funding as a consultant from American Specialty Health.

Objectives: To determine the relationship between consumer cost sharing for branded antidepressants and the initiation of branded therapy among patients with major depressive disorder (MDD) filling a prescription for generic MDD medication., Study Design: Retrospective cross-sectional analyses., Methods: Patients aged 18 to 64 years with MDD who filled a generic antidepressant were identified in commercial claims data for 2012 to 2014. For each year-specific analysis, an average cost-sharing index for branded antidepressants at the level of the plan was computed. Multivariable models were used to estimate the relationship between plan-level cost sharing for branded antidepressant medications and the filling of branded prescriptions, with demographic and clinical variables as covariates., Results: For patients with MDD filling a generic prescription, increases in branded cost sharing were associated with significant decreases in the likelihood of filling a branded antidepressant in each year (P <.001). Results in 2012 imply that a shift from the 0th to 90th percentile in the branded cost-sharing index corresponded with a 9.5% decrease in the relative likelihood of a branded fill among patients receiving a generic antidepressant. The corresponding figures for 2013 and 2014 were 9.3% and 3.5%, respectively., Conclusions: In MDD, patients and clinicians who dutifully adhere to guidelines requiring a trial of first-line medication may ultimately require therapy with alternate agents to achieve adequate disease control. A "reward the good soldier" benefit design would lower cost sharing for higher-tier evidence-based therapies when clinically indicated. Results suggest that narrowing the gap in cost sharing between branded and generic medications following a trial of a generic agent might improve access to second-line treatment in MDD.

Objective: Effectiveness of collaborative care for perinatal depression has been demonstrated for MOMCare, from early pregnancy up to 15 months postpartum, for Medicaid enrollees in a public health system. MOMCare had a greater impact on reducing depression and improving functioning for women with comorbid posttraumatic stress disorder (PTSD) than for those without PTSD. This study estimated the incremental benefit and cost and the net benefit of MOMCare for women with major depression and PTSD., Methods: A randomized trial (September 2009 to December 2014) compared the MOMCare collaborative care depression intervention (choice of brief interpersonal psychotherapy or pharmacotherapy or both) with enhanced maternity support services (MSS-Plus) in the public health system of Seattle-King County. Among pregnant women with a probable diagnosis of major depression or dysthymia (N=164), two-thirds (N=106) met criteria for probable PTSD. Blinded assessments at three, six, 12, and 18 months postbaseline included the Symptom Checklist-20 depression scale and the Cornell Services Index. Analyses of covariance estimated gain in depression free days (DFDs) by intervention and PTSD status., Results: When the analysis controlled for baseline depression severity, women with probable depression and PTSD in MOMCare had 68 more depression-free days over 18 months than those in MSS-Plus (p<.05). The additional depression care cost per MOMCare participant with comorbid PTSD was $1,312. The incremental net benefit of MOMCare was positive if a DFD was valued at ≥$20., Conclusions: For women with probable major depression and PTSD, MOMCare had significant clinical benefit over MSS-Plus, with only a moderate increase in health services cost.

Aims: The aim of this systematic review of economic evaluations alongside randomised controlled trials (RCTs) was to provide a comprehensive overview of the evidence concerning cost-effectiveness analyses of common treatment options for major depression., Methods: An existing database was used to identify studies reporting cost-effectiveness results from RCTs. This database has been developed by a systematic literature search in the bibliographic databases of PubMed, PsychINFO, Embase and Cochrane library from database inception to December 2014. We evaluated the quality of economic evaluations using a 10-item short version of the Drummond checklist. Results were synthesised narratively. The risk of bias of the included RCTs was assessed, based on the Cochrane risk of bias assessment tool., Results: Fourteen RCTs were included from the 5580 articles screened on titles and abstracts. The methodological quality of the health economic evaluations was relatively high and the majority of the included RCTs had low risk of bias in most of Cochrane items except blinding of participants and personnel. Cognitive behavioural therapy was examined in seven trials as part of a variety of treatment protocols and seems cost-effective compared with pharmacotherapy in the long-term. However cost-effectiveness results for the combination of psychotherapy with pharmacotherapy are conflicting and should be interpreted with caution due to limited comparability between the examined trials. For several treatments, only a single economic evaluation was reported as part of a clinical trial. This was the case for comparisons between different classes of antidepressants, for several types of psychotherapy (behavioural activation, occupational therapy, interpersonal psychotherapy, short-term psychotherapy, psychodynamic psychotherapy, rational emotive behavioural therapy, solution focused therapy), and for transcranial magnetic stimulation v. electroconvulsive therapy. The limited evidence base for these interventions means generalisations, based on economic evaluation alongside clinical trials, cannot easily be made., Conclusions: There is some economic evidence underpinning many of the common treatment options for major depression. Wide variability was observed in study outcomes, probably attributable to differences in population, interventions or follow-up periods. For many interventions, only a single economic evaluation alongside clinical trials was identified. Thus, significant economic evidence gaps remain in the area of major depressive disorder.

Background: Patients frequently require several lines of therapy for treatment of major depressive episodes. This economic analysis details the management of patients who responded inadequately due to lack of efficacy or intolerability to two previous antidepressants in the UK., Methods: The model included a decision tree and a Markov component. Health states considered in the decision tree were remission, response, no response, withdrawal due to adverse events, relapse, recovery, and recurrence. The time horizon was 24 months. Patients were on third-line treatment for up to a 3-month acute phase and a 6-month maintenance phase. As third-line efficacy data were not available, inputs were calculated by adjusting original second-line data to third-line based on proportionate reductions observed in STAR*D. Equivalent efficacy was assumed for all comparators. Healthcare resource use and utilities were based on UK estimates., Results: Vortioxetine was a cost-effective treatment option at a threshold of £20,000/QALY vs. escitalopram, citalopram, sertraline, and was associated with more health benefits, less costs (was dominant) versus relevant third-line comparators venlafaxine and duloxetine. Agomelatine was found not to be a cost-effective option. The 22-month maintenance phase treatment scenario results were similar to the 6-month base case., Limitations: Third-line efficacy data were not available. This highlights the need for studies in patients receiving third-line treatment., Conclusion: This model provides an overview for the management of patients receiving third-line treatment where limited evidence currently exists. Vortioxetine, with its novel mechanism of action, is expected to be a dominant treatment option versus relevant comparators in the UK., (Copyright © 2017. Published by Elsevier B.V.)

Background: Approximately 30-50% of patients with major depressive disorder can be classed as treatment resistant, widely defined as a failure to respond to two or more adequate trials of antidepressants in the current episode. Treatment resistant depression is associated with a poorer prognosis and higher mortality rates. One treatment option is to augment an existing antidepressant with a second agent. Lithium and the atypical antipsychotic quetiapine are two such add-on therapies and are currently recommended as first line options for treatment resistant depression. However, whilst neither treatment has been established as superior to the other in short-term studies, they have yet to be compared head-to-head in longer term studies, or with a superiority design in this patient group., Methods: The Lithium versus Quetiapine in Depression (LQD) study is a parallel group, multi-centre, pragmatic, open-label, patient randomised clinical trial designed to address this gap in knowledge. The study will compare the clinical and cost effectiveness of the decision to prescribe lithium or quetiapine add-on therapy to antidepressant medication for patients with treatment resistant depression. Patients will be randomised 1:1 and followed up over 12 months, with the hypothesis being that quetiapine will be superior to lithium. The primary outcomes will be: (1) time to all-cause treatment discontinuation over one year, and (2) self-rated depression symptoms rated weekly for one year via the Quick Inventory of Depressive Symptomatology. Other outcomes will include between group differences in response and remission rates, quality of life, social functioning, cost-effectiveness and the frequency of serious adverse events and side effects., Discussion: The trial aims to help shape the treatment pathway for patients with treatment resistant depression, by determining whether the decision to prescribe quetiapine is superior to lithium. Strengths of the study include its pragmatic superiority design, broad inclusion criteria (external validity) and longer follow up than previous studies., Trial Registration: ISRCTN registry: ISRCTN16387615 , registered 28 February 2016. ClinicalTrials.gov: NCT03004521 , registered 17 November 2016.

Background: Although the symptoms of major depressive disorder (MDD) are often manageable with pharmacotherapy, response to first-line antidepressant treatment is often less than optimal. This study describes long-term treatment patterns in MDD patients in the United States and quantifies the economic burden associated with different treatment patterns following first-line antidepressant therapy., Methods: MDD patients starting first-line antidepressant monotherapy and having continuous enrollment ≥12 months before and ≥24 months following the index date (i.e., the first documented prescription fill) were selected from the Truven Health Analytics MarketScan (2003-2014) database. Based on the type of first treatment change following initiation, six treatment cohorts were defined a priori ("persistence"; "discontinuation"; "switch"; "dose escalation"; "augmentation"; and "combination"). Treatment patterns through the fourth line of therapy within each cohort, healthcare resource utilization (HCRU), and cost analyses were restricted to patients with adequate treatment duration (defined as ≥42 days) in each line (analysis sub-sample, N = 21,088). HCRU and costs were described at the cohort and pattern levels. Treatment cohorts representing <5% of the analysis sub-sample were decided a priori not to be analyzed due to limited sample size., Results: 39,557 patients were included. Mean age was 42.1 years, 61.1% of patients were female, and mean follow-up was 4.1 years. Among the analysis sub-sample, the discontinuation (49.1%), dose escalation (37.4%), and switch (6.6%) cohorts were the most common of all treatment cohorts. First-line antidepressant discontinuation without subsequent MDD pharmacotherapy (22.9%) and cycling between discontinuation and resumption (11.2%) were the two most common treatment patterns. Median time to discontinuation was 23 weeks. The switch cohort exhibited the highest HCRU (18.9 days with medical visits per-patient-per-year) and greatest healthcare costs ($11,107 per-patient-per-year) following the index date. Treatment patterns representing a cycling on and off treatment in the switch cohort were associated with the greatest healthcare costs overall., Conclusion: A high proportion of patients discontinue first-line antidepressant shortly after initiation. Patterns representing a cycling on and off treatment in the switch cohort were associated with the highest healthcare costs. These findings underscore challenges in effectively treating patients with MDD and a need for personalized patient management.

Background: To assess the cost-utility of vortioxetine versus relevant comparators (agomelatine, bupropion SR, sertraline, and venlafaxine XR) in the finnish setting in major depressive disorder (MDD) patients with inadequate response to selective serotonin- /serotonin-norepinephrine reuptake inhibitors., Methods: A one-year analysis was conducted using a decision tree with a Markov state transition component. The health states were remission, relapse and recovery. A Finnish healthcare payer perspective was adopted., Results: Vortioxetine was less costly and more effective versus all comparators in both direct and societal perspectives. Vortioxetine reduced the average annual direct costs by 4% versus venlafaxine XR and 8% versus sertraline. The greater efficacy associated with vortioxetine was translated into a higher percentage of patients in remission and recovery. The model was most sensitive to changes in remission rates at 8 weeks., Conclusion: This cost-utility analysis showed vortioxetine to be a good alternative for MDD patients switching therapy in Finland.

Objective: This study aims to conduct an evidence review of the effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment for major depressive disorder., Methods: We searched MEDLINE®, the Cochrane Central Registry of Controlled Trials, and PsycINFO through February 2017. We used prespecified criteria to select studies, abstract data, and rate internal validity and strength of the evidence (PROSPERO number CRD42016036358)., Results: We included two randomized trials (RCT), five controlled cohort studies, and six modeling studies of mostly women in their mid-40s with few comorbidities. CNSDose (ABCB1, ABCC1, CYP2C19, CYP2D6, UGT1A1) is the only pharmacogenomics test that significantly improved remission (one additional remitting patient in 12 weeks per three genotyped, 95% CI 1.7 to 3.5) and reduced intolerability in an RCT. ABCB1 genotyping leads to one additional remitting patient in 5 weeks per three genotyped (95% CI 3 to 20), but tolerability was not reported. In an RCT, GeneSight (CYP2D6, CYPC19, CYP1A2, SLC6A4, HTR2A) did not statistically significantly improve remission, and evidence is inconclusive about its tolerability. Evidence is generally low strength because RCTs were few and underpowered. Cost-effectiveness is unclear due to lack of directly observed cost-effectiveness outcomes. We found no studies that evaluated whether pharmacogenomics shortens time to optimal treatment, whether improvements were due to switches to genetically congruent medication, or whether effectiveness varies based on test and patient characteristics., Conclusions: Certain pharmacogenomics tools show promise of improving short-term remission rates in women in their mid-40s with few comorbidities. But, important evidence limitations preclude recommending their widespread use and indicate a need for further research.

Preclinical Research Major depressive disorder (MDD) is a major psychiatric illness and it is predicted to be the second leading cause of disability by 2020 with a lifetime prevalence of about 13%. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used therapeutic class for MDD. However, response to SSRI treatment varies considerably between patients. Biomarkers of treatment response may enable clinicians to target the appropriate drug for each patient. Biomarkers need to have accuracy in real life, sensitivity, specificity, and relevance to depression. Introduction of MDD biomarkers into the health care system can increase the overall cost of clinical diagnosis of patients. Because of that, decisions to allocate health research funding must be based on drug effectiveness and cost-effectiveness. The assessment of MDD biomarkers should include reliable evidence of associated drug effectiveness, adverse events and consequences (reduced productivity and quality of life, disability) and effectiveness of alternative approaches, other drug classes or behavioral or alternative therapies. In addition, all the variables included in an economic model (probabilities, outcomes, and costs) should be based on reliable evidence gained from the literature-ideally meta-analyses-and the evidence should also be determined by informed and specific expert opinion. Early assessment can guide decisions about whether or not to continue test development, and ideally to optimize the process. Drug Dev Res 77 : 374-378, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: To assess the cost-effectiveness of vortioxetine versus venlafaxine XR (extended-release) in major depressive disorder (MDD) patients in South Korea., Methods: A 1-year cost-effectiveness analysis from a limited societal perspective was performed using a combined model consisting of a decision-tree and a Markov model. Patients entered the model when initiating or switching antidepressant treatment following inadequate response to previous treatment. Remission, relapse and recovery were the main health states., Results: Vortioxetine dominated venlafaxine XR, with quality-adjusted life year (QALY) gains of 0.0131 and cost savings of KRW 623,229/year [US$530/year] from a limited societal perspective. Safety contributed more than efficacy to the incremental QALY gains. More patients were in recovery after initial treatment and after 1 year with vortioxetine (31%, 40%) compared to venlafaxine XR (23%, 36%). Vortioxetine remained dominant in 98% of probabilistic simulations., Conclusion: Vortioxetine dominated venlafaxine XR in South Korea and is a relevant treatment option for MDD patients initiating or switching therapy.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of vortioxetine (Lundbeck) to submit clinical and cost-effectiveness evidence for vortioxetine for the treatment of major depressive episodes (MDEs), as part of the Institute's Single Technology Appraisal (STA) process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and the resulting NICE guidance TA367 issued in November 2015. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. Two phase III randomised controlled trials for a second-line population involving vortioxetine were identified-REVIVE and TAK318. These two trials represent only 972 of over 7000 patients included in trials of vortioxetine. In REVIVE, there was a statistically significant difference in depression scores favouring vortioxetine compared with agomelatine [mean Montgomery-Åsberg Depression Rating Scale (MADRS) score difference of 2.16 points; 95 % confidence interval 0.81-3.51]. The ERG concluded that, based on all the evidence, rather than the substantially restricted subset of evidence originally considered by the manufacturer, vortioxetine is likely to be similar in efficacy to other analysed antidepressants [citalopram, sertraline, escitalopram and venlafaxine extended release (XR)], and may be more efficacious than agomelatine and inferior to duloxetine. The ERG concluded that vortioxetine may be more tolerable than other analysed antidepressants (sertraline, venlafaxine XR and bupropion), although the limited data prevent firm conclusions. The base-case incremental cost-effectiveness ratio (ICER) of vortioxetine reported by the manufacturer was £378 per quality-adjusted life-year (QALY) compared with venlafaxine. Given considerable concerns about the indirect treatment comparison undertaken by the manufacturer, the use of only a restrictive subset of the available evidence, and concerns regarding comparators and structural model assumptions, the ERG believes that this is not a valid estimate of the cost effectiveness of vortioxetine. Following corrections made to the model made by the ERG, the estimated cost effectiveness of vortioxetine was sensitive to the source of evidence used, in addition to whether certain comparators were excluded. The NICE thus asked the manufacturer to provide a revised economic model, which incorporated the broader evidence base and considered the cost effectiveness of vortioxetine as a third-line treatment. Assuming equal efficacy, vortioxetine was shown to be less costly and generate a higher QALY gain than relevant comparators at the third-line of treatment owing to its tolerability and adverse event profile. The NICE Appraisal Committee recommended vortioxetine as an option for treating MDEs in adults whose condition has responded inadequately to two antidepressants within the current episode.

Background: The prevalence of depressive disorder in adults with advanced cancer is around 20 %. Although cognitive behavioural therapy (CBT) is recommended for depression and may be beneficial in depressed people with cancer, its use for depression in those with advanced disease for whom cure is not likely has not been explored., Methods: People aged 18 years and above with advanced cancer attending General Practitioner (GP), oncology or hospice outpatients from centres across England will be screened to establish a DSM-IV diagnosis of depression. Self-referral is also accepted. Eligible consenters will be randomised to a single blind, multicentre, randomised controlled trial of the addition to treatment as usual (TAU) of up to 12 one-hour weekly sessions of manualised CBT versus TAU alone. Sessions are delivered in primary care through Increasing Access to Psychological Care (IAPT) service, and the manual includes a focus on issues for people approaching the end of life. The main outcome is the Beck Depression Inventory-II (BDI-II). Subsidiary measures include the Patient Health Questionnaire, quality of life measure EQ-5D, Satisfaction with care, Eastern Cooperative Oncology Group-Performance Status and a modified Client Service Receipt Inventory. At 90 % power, we require 240 participants to enter the trial. Data will be analysed using multi-level (hierarchical) models for data collected at baseline, 6, 12, 18 and 24 weeks. Cost effectiveness analysis will incorporate costs related to the intervention to compare overall healthcare costs and QALYs between the treatment arms. We will conduct qualitative interviews after final follow-up on patient and therapist perspectives of the therapy., Discussion: This trial will provide data on the clinical and cost effectiveness of CBT for people with advanced cancer and depression. We shall gain an understanding of the feasibility of delivering care to this group through IAPT. Our findings will provide evidence for policy-makers, commissioners and clinicians in cancer and palliative care, and in the community., Trial Registration: Controlled Trials ISRCTN07622709 , registered 15 July 2011.

Background: Individuals with a history of recurrent depression have a high risk of repeated depressive relapse/recurrence. Maintenance antidepressant medication (m-ADM) for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to m-ADM. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce the risk of relapse/recurrence compared with usual care but has not yet been compared with m-ADM in a definitive trial., Objectives: To establish whether MBCT with support to taper and/or discontinue antidepressant medication (MBCT-TS) is superior to and more cost-effective than an approach of m-ADM in a primary care setting for patients with a history of recurrent depression followed up over a 2-year period in terms of preventing depressive relapse/recurrence. Secondary aims examined MBCT's acceptability and mechanism of action., Design: Single-blind, parallel, individual randomised controlled trial., Setting: UK general practices., Participants: Adult patients with a diagnosis of recurrent depression and who were taking m-ADM., Interventions: Participants were randomised to MBCT-TS or m-ADM with stratification by centre and symptomatic status. Outcome data were collected blind to treatment allocation and the primary analysis was based on the principle of intention to treat. Process studies using quantitative and qualitative methods examined MBCT's acceptability and mechanism of action., Main Outcomes Measures: The primary outcome measure was time to relapse/recurrence of depression. At each follow-up the following secondary outcomes were recorded: number of depression-free days, residual depressive symptoms, quality of life, health-related quality of life and psychiatric and medical comorbidities., Results: In total, 212 patients were randomised to MBCT-TS and 212 to m-ADM. The primary analysis did not find any evidence that MBCT-TS was superior to m-ADM in terms of the primary outcome of time to depressive relapse/recurrence over 24 months [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.67 to 1.18] or for any of the secondary outcomes. Cost-effectiveness analysis did not support the hypothesis that MBCT-TS is more cost-effective than m-ADM in terms of either relapse/recurrence or quality-adjusted life-years. In planned subgroup analyses, a significant interaction was found between treatment group and reported childhood abuse (HR 1.89, 95% CI 1.06 to 3.38), with delayed time to relapse/recurrence for MBCT-TS participants with a more abusive childhood compared with those with a less abusive history. Although changes in mindfulness were specific to MBCT (and not m-ADM), they did not predict outcome in terms of relapse/recurrence at 24 months. In terms of acceptability, the qualitative analyses suggest that many people have views about (dis)/continuing their ADM, which can serve as a facilitator or a barrier to taking part in a trial that requires either continuation for 2 years or discontinuation., Conclusions: There is no support for the hypothesis that MBCT-TS is superior to m-ADM in preventing depressive relapse/recurrence among individuals at risk for depressive relapse/recurrence. Both treatments appear to confer protection against relapse/recurrence. There is an indication that MBCT may be most indicated for individuals at greatest risk of relapse/recurrence. It is important to characterise those most at risk and carefully establish if and why MBCT may be most indicated for this group., Trial Registration: Current Controlled Trials ISRCTN26666654., Funding: This project was funded by the NIHR Health Technology Assessment programme and the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South West Peninsula and will be published in full in Health Technology Assessment; Vol. 19, No. 73. See the NIHR Journals Library website for further project information.

Background: Major depressive disorder is one of the most common and disabling mental health disorders and is associated with substantial costs in terms of direct health care utilization and workplace productivity. Cognitive dysfunction, which alone substantially increases health care costs, is commonly associated with major depressive disorder. However, the health care costs of cognitive dysfunction in the context of depressive disorder are unknown. Recovery from mood symptoms is not always associated with resolution of cognitive dysfunction. Thus, cognitive dysfunction may contribute to health care burden even with successful antidepressant therapy. , Objective: To compare health care utilization and costs for patients with a depressive disorder with and without cognitive dysfunction, at 3 and 6 months after initiation of antidepressant medication. , Methods: This was an observational study, combining a cross-sectional patient survey, administered during a telephone interview, with health care claims data from a large, geographically diverse U.S. health plan. Included patients had at least 1 pharmacy claim for an antidepressant medication between August 1 and September 30, 2012, and no claim for any antidepressant during the 6 months prior to the index date. In addition to other criteria assessed in the claims data, patients confirmed a diagnosis of depression or major depressive disorder and the absence of any exclusionary neurological diagnoses possibly associated with cognitive impairment. Eligible patients were administered validated cognitive function assessments of verbal episodic memory (Hopkins Verbal Learning Test-Revised, Delayed and Total); attention (Digit Span Forward Maximum Sequence Length); working memory (Digit Span Backward Maximum Sequence Length); and executive function (D-KEFS-Letter Fluency Test). Based on comparison of scores with normative data, patients were assigned to cognitive dysfunction or cognitive normal cohorts. All-cause (all diagnoses) and depressive disorder-related health care utilization and costs (all from a payer perspective) were assessed 6 months prior (baseline) to antidepressant initiation and 3 months and 6 months after (follow-up) initiation of antidepressant medication. Health care utilization and costs included ambulatory (office and hospital outpatient), emergency room, inpatient hospital, pharmacy, other medical (e.g., laboratory and diagnostics), and total (all categories combined). All-cause and depressive disorder-related total costs during the 3- and 6-month follow-up periods were modeled with generalized linear modeling with gamma distribution and log link, while adjusting for potential confounders (age, race, gender, education, employment, and comorbidities)., Results: Of the 13,537 patients who were mailed an invitation, 824 (6%) were eligible and agreed to participate. Of these, 563 patients provided informed consent, completed the interview, maintained eligibility, and were included in the 3-month calculations. Among these, 255 (45%) were classified as having cognitive dysfunction. Mean patient age was 41.3 (± 12.5) years; 80% were female. Most patients were white and employed. More patients in the cognitive normal cohort were white (P  less than  0.001) and employed full time (P = 0.029), had higher education attainment (P  less than    0.001), and had fewer comorbidities (P = 0.007) than those in the cognitive dysfunction cohort. Over the first 3 months, patients with cognitive dysfunction had higher adjusted all-cause costs ($3,309 vs. $2,157, P = 0.002) and higher adjusted depressive disorder-related costs ($718 vs. $406, P  less than  0.001) than patients without cognitive dysfunction. At 6 months, data from 4 patients were removed from the analysis because of exclusionary diagnoses. Over 6 months, patients with cognitive dysfunction had higher adjusted all-cause costs ($4,793) than patients without cognitive dysfunction ($3,683, P = 0.034). Over 6 months, depressive disorder-related costs did not significantly differ between patients with ($771) and without cognitive dysfunction ($594, P = 0.071). The main drivers of all-cause costs were office visits, outpatient hospital visits, and inpatient costs, and the main driver of depressive disorder-related costs was inpatient costs., Conclusions: Cognitive dysfunction was associated with higher adjusted all-cause and depressive disorder-related costs 3 months after initiation of an antidepressant medication. This difference persisted for all-cause costs through 6 months. Identification and treatment of cognitive dysfunction in patients with depressive disorder might reduce health care costs.

Background: Major depressive disorder (MDD) impacts health, quality of life and workplace productivity. Antidepressant treatment is the primary therapeutic intervention. This study assessed the efficacy and tolerability of new generation antidepressants and their cost-effectiveness in the Singapore healthcare system., Methods: We conducted a systematic search for head-to-head randomised controlled trials on ten antidepressants (agomelatine, duloxetine, escitalopram, fluvoxamine, fluoxetine, mirtazapine, paroxetine, sertraline, trazodone and venlafaxine) employed as monotherapy in acute MDD management. We performed a network meta-analysis to compare their relative efficacy. The outcome measures for efficacy were response and remission rate, and mean change in Hamilton Depression Rating Scale (HDRS) score; and for tolerability, study withdrawal rates due to adverse events. To evaluate their relative cost effectiveness, a decision tree simulating a cohort of MDD patients using antidepressant as monotherapy was constructed from a societal perspective over 6 months. We used effectiveness data from our network meta-analysis and local data on resource use for depression in Singapore. The incremental cost expected for each additional quality-adjusted life-year (QALY) gained was calculated and presented as the incremental cost-effectiveness ratio (ICER)., Results: We identified 76 relevant articles for the network meta-analysis. Of the ten agents included in the analysis, mirtazapine and agomelatine were most efficacious in achieving response and remission, respectively. Mirtazapine and duloxetine resulted in the greatest magnitude of change in the HDRS score. Agomelatine, escitalopram and sertraline were the best tolerated of the drugs analysed, while duloxetine was the least well tolerated drug. Using a composite outcome of efficacy (response and remission rates) and tolerability, agomelatine, escitalopram and mirtazapine were the favoured treatments. In the cost-effectiveness analysis, apart from agomelatine, all the treatments were dominated by mirtazapine. Against mirtazapine, agomelatine was not cost effective given that its ICER exceeded the threshold value., Conclusion: Agomelatine, escitalopram and mirtazapine had favourable balance between efficacy and tolerability. In addition, mirtazapine was a cost-effective option in the Singapore healthcare system.

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., (Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objectives: To describe the lifetime outcomes and economic implications of combinatorial pharmacogenomic (CPGx) testing versus treatment as usual (TAU) psychopharmacologic medication selection for a representative major depressive disorder patient who has not responded to previous treatment(s)., Study Design: Markov state-transition analysis based on clinical studies., Methods: Clinical validity and utility were based on published findings in prospective clinical studies of a commercially available CPGx test. Data for quality of life, direct costs, and indirect costs were extracted from meta-analyses of published literature on clinical studies and claims databases. Outcomes were assessed from a societal perspective, and included differences between the CPGx and the TAU strategies in quality-adjusted life-years (QALYs), cumulative direct and indirect costs, and cost per QALY gained., Results: CPGx improved the treatment response rate by 70% (1.7 times as high as that with TAU), increasing QALYs by 0.316 years. With these health benefits, CPGx is expected to save $3711 in direct medical costs per patient and $2553 in work productivity costs per patient over the lifetime. The cost-effectiveness of CPGx testing was robust over a wide range of variation in the input parameters, including the scenario when testing efficacy was set to its lower limit., Conclusions: CPGx testing has been shown by prospective studies to modify treatment decisions for patients nonresponsive to previous treatment(s), with increased rates of treatment response. These effects are projected to increase quality-adjusted survival, and to save both direct and indirect costs to individual patients and society generally.

Background: Clinical practice guidelines for the treatment of major depressive disorder (MDD) recommend antidepressants for patients with moderate-severe depression and active monitoring for patients with mild-moderate symptoms. The feasibility and efficiency of active monitoring has not been proven conclusively. The aim of this study is to evaluate the cost-effectiveness of active monitoring in comparison to antidepressants for primary care patients with mild-moderate MDD., Methods/design: This is a 12-month follow-up multicenter observational prospective controlled trial. Patients are enrolled in 12 primary care centers in Barcelona (Spain). Eligible patients are adults (≥18 years-old) with a new episode of MDD that sign a written consent to participate. This is a naturalistic study in which general practitioners (GPs) use their professional judgment to allocate patients into active monitoring or antidepressants groups. GPs treat the patients following their clinical criteria. At baseline, GPs complete a questionnaire (sociodemographic/job characteristics, training, attitude towards depression, interest on mental health and participation in communication groups). Patients' measurements take place at baseline and after six and 12 months. Main outcome measures include severity of depression (PHQ-9), health-related quality of life (EuroQol-5D) and use of healthcare and social care services (Client Service Receipt Inventory). Secondary outcomes include diagnosis of MDD according to DSM-IV diagnostic criteria (SCID-I), disability (WHO-DAS), anxiety (BAI), comorbidities, medication side-effects and beliefs about medicines (BMQ). The analysis will be done according to the intention to treat analysis. Missing data will be imputed using multiple imputation by chained equations. To minimize the bias resulting from the lack of randomization, a propensity score will be used. Incremental effects and costs between groups will be modelled in each of the imputed databases using multivariate generalized linear models and then combined as per Rubin's rules. Propensity scores will be used to adjust the models. Incremental cost-effectiveness ratios will be calculated by dividing the difference in costs between groups by the difference in effects. To deal with the uncertainty, resampling techniques with bootstrapping will be used and cost-effectiveness planes and cost-effectiveness acceptability curves will be constructed. A series of sensitivity analyses will be performed., Discussion: Given the high burden and costs generated by depressive disorder, it is important that general practitioners treat major depression efficiently. Recent evidence has suggested that antidepressants have low benefits for patients with mild to moderate major depression. For such cases of depression, active monitoring exists as a treatment option, but it is not without difficulties for implementation and its effectiveness and efficiency have not been demonstrated conclusively. The results of the study will provide information on which is the most efficient approach to treat patients with mild to moderate major depression in primary care., Trial Registration: ClinicalTrials.gov: NCT02245373.

Background: Depression accounts for the greatest disease burden of all mental health disorders, contributes heavily to healthcare costs, and by 2020 is set to become the second largest cause of global disability. Although 10% to 16% of people aged 65 years and over are likely to experience depressive symptoms, the condition is under-diagnosed and often inadequately treated in primary care. Later-life depression is associated with chronic illness and disability, cognitive impairment and social isolation. With a progressively ageing population it becomes increasingly important to refine strategies to identity and manage depression in older people. Currently, management may be limited to the prescription of antidepressants where there may be poor concordance; older people may lack awareness of psychosocial interventions and general practitioners may neglect to offer this treatment option., Methods/design: CASPER Plus is a multi-centre, randomised controlled trial of a collaborative care intervention for individuals aged 65 years and over experiencing moderate to severe depression. Selected practices in the North of England identify potentially eligible patients and invite them to participate in the study. A diagnostic interview is carried out and participants with major depressive disorder are randomised to either collaborative care or usual care. The recruitment target is 450 participants. The intervention, behavioural activation and medication management in a collaborative care framework, has been adapted to meet the complex needs of older people. It is delivered over eight to 10 weekly sessions by a case manager liaising with general practitioners. The trial aims to evaluate the clinical and cost effectiveness of collaborative care in addition to usual GP care versus usual GP care alone. The primary clinical outcome, depression severity, will be measured with the Patient Health Questionnaire-9 (PHQ-9) at baseline, 4, 12 and 18 months. Cost effectiveness analysis will assess health-related quality of life using the SF-12 and EQ-5D and will examine cost-consequences of collaborative care. A qualitative process evaluation will be undertaken to explore acceptability, gauge the extent to which the intervention is implemented and to explore sustainability beyond the clinical trial., Discussion: Results will add to existing evidence and a positive outcome may lead to the commissioning of this model of service in primary care., Trial Registration: ISRCTN45842879 (24 July 2012).

Objective: The objective of this study was to assess the cost effectiveness of commonly used antidepressants as first-line treatment of major depressive disorder (MDD) in Belgium., Methods: The model structure was based on a decision tree developed by the Swedish TLV (Tandvårds- och läkemedelsförmånsverket) and adapted to the Belgium healthcare setting, using primary local data on the patterns of treatment and following KCE [Federal Knowledge Center (Federaal Kenniscentrum voor de Gezondheidszorg)] recommendations. Comparators were escitalopram, citalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, and mirtazapine. In the model, patients not achieving remission or relapsing after remission on the assessed treatment moved to a second therapeutic step (titration, switch, add-on, or transfer to a specialist). In case of failure in the second step or following a suicide attempt, patients were assumed to be referred to secondary care. The time horizon was 1 year and the analysis was conducted from the National Institute for Health and Disability Insurance (NIHDI; national health insurance) and societal perspectives. Remission rates were obtained from the TLV network meta-analysis and risk of relapse, efficacy following therapeutic change, risk of suicide attempts and related death, utilities, costs (2012), and resources were derived from the published literature and expert opinion. The effect of uncertainty in model parameters was estimated through scenario analyses and a probabilistic sensitivity analysis (PSA)., Results: In the base-case analysis, escitalopram was identified as the optimal strategy: it dominated all other treatments except venlafaxine from the NIHDI perspective, against which it was cost effective with an incremental cost-effectiveness ratio of 6,352 per quality-adjusted life-year (QALY). Escitalopram also dominated all other treatments from the societal perspective. At a threshold of 30,000 per QALY and from the NIHDI perspective, the PSA showed that the probability of escitalopram being identified as the optimal strategy ranged from 61 % (vs. venlafaxine) to 100 % (vs. fluoxetine)., Conclusion: Escitalopram was associated with the highest probability of being the optimal treatment from the NIHDI and societal perspectives. This analysis, based on new Belgian clinical practice data and following KCE requirements, provides additional information that may be used to guide the choice of treatments in the management of MDD in Belgium.

Objective: A review of existing economic models in major depressive disorder (MDD) highlighted the need for models with longer time horizons that also account for heterogeneity in treatment pathways between patients. A core discrete event simulation model was developed to estimate health and cost outcomes associated with alternative treatment strategies., Methods: This model simulated short- and long-term clinical events (partial response, remission, relapse, recovery, and recurrence), adverse events, and treatment changes (titration, switch, addition, and discontinuation) over up to 5 years. Several treatment pathways were defined on the basis of fictitious antidepressants with three levels of efficacy, tolerability, and price (low, medium, and high) from first line to third line. The model was populated with input data from the literature for the UK setting. Model outputs include time in different health states, quality-adjusted life-years (QALYs), and costs from National Health Service and societal perspectives. The codes are open source., Results: Predicted costs and QALYs from this model are within the range of results from previous economic evaluations. The largest cost components from the payer perspective were physician visits and hospitalizations. Key parameters driving the predicted costs and QALYs were utility values, effectiveness, and frequency of physician visits. Differences in QALYs and costs between two strategies with different effectiveness increased approximately twofold when the time horizon increased from 1 to 5 years., Conclusion: The discrete event simulation model can provide a more comprehensive evaluation of different therapeutic options in MDD, compared with existing Markov models, and can be used to compare a wide range of health care technologies in various groups of patients with MDD., (Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients., (Copyright © 2013 Wiley Publishing Asia Pty Ltd.)

Context: Treatment Resistant Depression (TRD) is a significant and burdensome health concern., Objective: To characterize, compare and understand the difference between TRD and non-TRD patients and episodes in respect of their episode duration, treatment patterns and healthcare resource utilization., Design and Setting: Patients between 18 and 64 years with a new diagnosis of major depressive disorder (MDD) and without a previous or comorbid diagnosis of schizophrenia or bipolar disease were included from PharMetrics Integrated Database, a claims database of commercial insurers in the US. Episodes of these patients in which there were at least two distinct failed regimens involving antidepressants and antipsychotics were classified as TRD., Patients: 82,742 MDD patients were included in the analysis; of these patients, 125,172 episodes were identified (47,654 of these were drug-treated episodes)., Main Outcome Measures: Comparison between TRD and non-TRD episodes in terms of their duration, number and duration of lines of treatment, comorbidities, and medical resource utilization., Results: Of the treated episodes, 6.6% (N = 3,134) met the criteria for TRD. The median time to an episode becoming TRD was approximately one year. The mean duration of a TRD episode was 1,004 days (vs. 452 days for a non-TRD episode). More than 75% of TRD episodes had at least four lines of therapy; half of the treatment regimens included a combination of drugs. Average hospitalization costs were higher for TRD than non-TRD episodes: $6,464 vs. $1,734, as were all other health care utilization costs., Conclusions: While this study was limited to relatively young and commercially covered patients, used a rigorous definition of TRD and did not analyze for cause or consequence, the results highlight high unmet medical need and burden of TRD on patients and health care resources.

Introduction: Major depressive disorder (MDD) is a common and disabling condition across the world. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the most commonly used antidepressants. The objective of this study was to assess the cost-effectiveness [€ per quality-adjusted life year (QALY)] of all SSRIs and all SNRIs for the treatment of MDD in Italy., Methods: A decision analytic model was adapted from the Swedish Dental and Pharmaceutical Benefits agency model to reflect current clinical practice in the treatment of MDD in the largest Italian regions. This adaptation was possible thanks to the collaboration of an expert panel of Italian psychiatrists and health economists. The model evaluated patients with a first diagnosis of MDD and initiating an SSRI or an SNRI for the first time. The time horizon was 12 months. Efficacy and utility data for the model were retrieved from the literature and validated by the expert panel. Local data were considered for resource utilization and for treatment costs based on each regional health service perspective. Population-weighted regional data were used to define a national model. Scenario simulations, one-way sensitivity analyses, and Monte Carlo simulations were performed to test the robustness of the model., Results: The base case analysis showed that escitalopram was associated with a lower total cost (€ 1,562) and a larger health gain (QALYs) at 1 year (0.732) per patient and dominated the other treatment strategies since more QALYs were achieved at a lower total cost. Sensitivity analyses support the robustness of the model., Conclusion: The results indicate that escitalopram is the most cost-effective pharmacological treatment strategy for the Italian health service compared with other SSRIs and all SNRIs used in the first-line treatment of MDD.

Background: The comorbidity of pain and depression is associated with high disease burden for patients in terms of disability, wellbeing, and use of medical care. Patients with major and minor depression often present themselves with pain to a general practitioner and recognition of depression in such cases is low, but evolving. Also, physical symptoms, including pain, in major depressive disorder, predict a poorer response to treatment. A multi-faceted, patient-tailored treatment programme, like collaborative care, is promising. However, treatment of chronic pain conditions in depressive patients has, so far, received limited attention in research. Cost effectiveness of an integrated approach of pain in depressed patients has not been studied., Methods/design: This study is a placebo controlled double blind, three armed randomized multi centre trial. Patients with (sub)chronic pain and a depressive disorder are randomized to either a) collaborative care with duloxetine, b) collaborative care with placebo or c) duloxetine alone. 189 completers are needed to attain sufficient power to show a clinically significant effect of 0.6 SD on the primary outcome measures (PHQ-9 score). Data on depression, anxiety, mental and physical health, medication adherence, medication tolerability, quality of life, patient-doctor relationship, coping, health resource use and productivity will be collected at baseline and after three, six, nine and twelve months., Discussion: This study enables us to show the value of a closely monitored integrated treatment model above usual pharmacological treatment. Furthermore, a comparison with a placebo arm enables us to evaluate effectiveness of duloxetine in this population in a real life setting. Also, this study will provide evidence-based treatments and tools for their implementation in practice. This will facilitate generalization and implementation of results of this study. Moreover, patients included in this study are screened for pain symptoms, differentiating between nociceptive and neuropathic pain. Therefore, pain relief can be thoroughly evaluated., Trial Registration: NTR1089.

Background: Major depressive disorder (MDD) constitutes an important public health problem, as it is highly prevalent in the industrialized world and it is associated with substantial economic consequences for patients, health care providers, insurance and social security organizations and employers. To conduct an economic evaluation comparing agomelatine with other commonly used alternatives for treating patients with major depressive disorder (MDD) in Greece., Methods: An existing international Markov model designed to evaluate the cost-effectiveness of agomelatine was adapted to the Greek setting. It reflects six different health states, in which patients may move on a monthly basis. The analysis was undertaken from a societal perspective. Transition probabilities, utilities and costs assigned to each health state were extracted from the published literature, government sources and expert opinion. Data reflects the year 2012 and was discounted using a rate of 3.5%. Probabilistic analysis was undertaken to deal with uncertainty., Results: Base case analyses revealed that agomelatine is a dominant therapy for MDD relative to escitalopram, fluoxetine and sertraline, and it appeared to be cost-effective compared to venlafaxine (ICER: €547/QALY). Agomelatine remained a dominant treatment against generic sertraline and fluoxetine, and it appeared to be a cost-effective alternative compared to generic venlafaxine and escitalopram (ICER: €1,446/QALY and €3,303/QALY, respectively). Excluding the indirect cost from the analysis, agomelatine remained a cost-effective alternative over all comparators. In the probabilistic sensitivity analysis agomelatine was dominant in 44.5%, 89.6%, 70.6% and 84.6% of simulated samples against branded venlafaxine, escitalopram, fluoxetine and sertraline, respectively., Conclusion: The present evaluation indicates that agomelatine is either a dominant or a cost-effective alternative relative to branded or generic alternatives, in Greece.

Aim: We aimed at estimating excess medical expenditures associated with major depressive disorder (MDD) among working-age adults diagnosed with diabetes, disaggregated by treatment mode: insulin-treated diabetes (ITDM) or non-insulin-treated diabetes (NITDM)., Methods: We analyzed data for over 500,000 individuals with diagnosed diabetes from the 2008 U.S. MarketScan claims database. We grouped diabetic patients first by treatment mode (ITDM or NITDM), then by MDD status (with or without MDD), and finally by whether those with MDD used antidepressant medication. We estimated annual mean excess outpatient, inpatient, prescription drug, and total expenditures using regression models, controlling for demographics, types of health coverage, and comorbidities., Results: Among persons having ITDM, the estimated annual total mean expenditure for those with no MDD (the comparison group) was $19,625. For those with MDD, the expenditures were $12,406 (63%) larger if using antidepressant medication and $7322 (37%) larger if not using antidepressant medication. Among persons having NITDM, the corresponding estimated expenditure for the comparison group was $10,746, the excess expenditures were $10,432 (97%) larger if using antidepressant medication and $5579 (52%) larger if not using antidepressant medication, respectively. Inpatient excess expenditures were the largest of total excess expenditure for those with ITDM and MDD treated with antidepressant medication; for all others with diabetes and MDD, outpatient expenditures were the largest excess expenditure., Conclusions: Among working-age adults with diabetes, MDD was associated with substantial excess medical expenditures. Implementing the effective interventions demonstrated in clinical trials and treatment guidelines recommended by professional organizations might reduce the economic burden of MDD in this population., Competing Interests: The authors report no conflicts of interest., (Published by Elsevier Ireland Ltd.)

Objective: To develop and apply a longitudinal model that adjusts for pre-treatment covariates to examine the trajectory of healthcare costs in duloxetine patients with major depressive disorder (MDD)., Methods: Retrospective healthcare cost data from Thomson Reuters Marketscan® Database included 10,987 patients with MDD, aged 18-64, receiving duloxetine at low (<60 mg/day), standard (60 mg/day), or high (>60 mg/day) initial doses. A linear mixed-effects model for repeated measures used dose, month, and dose*month as fixed effects and patient (dose) as a random effect, and adjusted for demographics, comorbidities, body system disorders, and prior medication history. Model goodness-of-fit was evaluated with R(2). Rates of change (slopes) were estimated from the fitted model and differences in the cost trajectory among dosing cohorts were tested using the F-test. Bootstrapping and propensity score (PS) stratification were conducted to provide sensitivity analyses., Results: Main effects and covariates were all significant (p < 0.05). Adjustment by pre-treatment covariates greatly improved the model fit (R(2 )= 0.43). The model revealed a significant increase in healthcare costs in the 6 months preceding and a significant decrease in the 6 months following duloxetine initiation for each initial dose cohort and the overall cohort (p < 0.05). In both the pre- and post-treatment periods, the high initial-dose cohort had higher healthcare costs than standard or low initial-dose cohorts (p < 0.05). Bootstrapping and PS stratification confirmed these test results., Limitations: The analyses performed here were based on non-randomized, observational data, and thus subject to potential biases due to unmeasured confounding., Conclusions: Longitudinal models, compared with conventional mean-based methods, provide better opportunities to assess changes in cost trajectory patterns around the time of changes in medical treatment. In insured patients with MDD started on duloxetine, healthcare costs increased before duloxetine initiation, perhaps signaling a clinical deterioration that led to a change in treatment strategy. Healthcare costs then decreased following duloxetine initiation.

Objective: To evaluate the compliance, persistence and costs of the treatment of major depressive disorder (MDD) in the setting of Primary Care, placing emphasis on the different aspects of those patients with an initial suboptimal response to antidepressant treatment., Design: A retrospective observational study using the population registers of Badalona Healthcare Services. The inclusion criteria consisted of; age ≥18 years, initial episode during 2008-2009, and to be on antidepressant treatment for at least 8 weeks after the first prescription. The follow-up was 12 months. Two study groups were formed, patients with suboptimal response, and remission., Main Measurements: Sociodemographic data, compliance and adherence to treatment, health costs (direct and indirect)., Results: A total of 2,260 subjects were analysed (mean age 58.8 years, 74% women). Just under half (42.7%, 95% CI; 40.0-46.4%) had a suboptimal response to the treatment. These patients had a higher mean age, a higher proportion of women, and pensioners, as well as higher comorbidity, compared to the remission group. They also had poorer compliance percentages (65.1% vs. 67.7%) and treatment persistence at 12 months (31.8% vs. 53.2%), respectively, P<.001. The annual health costs were, 826.1€ for patients with a suboptimal response vs. 451.2€ in patients in remission; loss of productivity 1,842.0€ vs. 991.4€, respectively; P<.001. The factors associated to a suboptimal response were; lack of compliance (OR=1.7), years with the disorder (OR=1.2), age (OR=1.1) and presence of comorbidity (OR=1.1)., Conclusions: The patients with an initial suboptimal response to antidepressant treatment had a higher comorbidity, lower therapeutic compliance, and incurred higher total costs, particularly in losses in work productivity., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

Background: The Mental Health Research Network and Dementia and Neurodegenerative Diseases Research Network were established in the UK to increase research capacity and activity; the former in mental health generally, and the latter specifically in neurodegenerative disorders including dementia. Little evidence exists on the impact of these networks on research in mental health of older people., Aims: To examine research network support to a multi-centre randomised controlled trial of antidepressants in people with depression superimposed on dementia. Method Qualitative questionnaires were completed by principal investigators, trial-funded research workers and clinical study officers (CSOs) of the research networks., Results: Research network contribution was much valued by principal investigators and the nine research teams. CSOs boosted the recruitment campaign in a challenging environment and enhanced assessment processes. Some problems with consistency and staff turnover were raised., Conclusion: Research network input can make an appreciable difference to the process and outcome of a multi-centre clinical trial.

Background: Switching to another antidepressant is one of the alternative treatment strategies employed in major depressive disorder (MDD) patients who have no remission despite an adequate trial of an antidepressant. The aim of the present study was to present an economic evaluation of sertraline compared with venlafaxine after unsuccessful treatment for depression with citalopram., Material and Method: An economic model was constructed in line with the design of the sequenced treatment alternatives to relieve depression (STAR*D) study. MDD patients who did not have a remission with or who had an intolerance to citalopram were randomly assigned to be switched to either sertraline or venlafaxine. Patients who had no remission at the end of the switching treatment phase still continued the antidepressants and received an adjunctive treatment with aripiprazole. The event probabilities were used to derive the transitional probabilities use in the model. The primary model outcome was remission of symptoms and the secondary outcome was quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICEs) were estimated for the costs per unit of effectiveness. Sensitivity analyses were done to assess the effects of model assumptions., Results: The total direct costs per remission were 27,830 Baht for sertraline and 30,147 Baht for venlafaxine. Sertraline had lower total costs per QALY than venlafaxine (34,788 Baht vs. 37,683 Baht). The more cost-effectiveness of sertraline resulted in 7.68% of cost saving. The incremental cost of venlafaxine compared with sertraline was 2,316 Baht per remission gained and 2895 Baht per QALY gained. By varying the remission rate of venlafaxine from 20% to 40%, the sensitivity analysis results in a decrease in total costs of venlafaxine from 31,926 Baht to 24,808 Baht. In addition, incremental cost per remission gained changed from 4096 Baht in favour of sertraline to 3023 Baht in favour of venlafaxine. Similarly, incremental cost per QALY gained changedfrom in favour of sertraline to in favour of venlafaxine., Conclusion: Based on the STAR*D trial, the results of the economic study indicate that a switch to sertraline is a cost-effectiveness treatment option compared with a switch to venlafaxine in MDD patients who have no remission or cannot tolerate citalopram.

Background: While the clinical utility of atypical antipsychotics has been established in patients with major depressive disorder (MDD) who are refractory to antidepressant therapy, their cost-effectiveness is unknown., Objective: To examine the cost-effectiveness of aripiprazole, quetiapine, and olanzapine/fluoxetine in adults with MDD who are refractory to antidepressant therapy., Methods: Using techniques of decision analysis, we estimated expected outcomes and costs over 6 weeks in adults with MDD receiving (1) aripiprazole 2-20 mg/day and antidepressant therapy; (2) quetiapine 150 mg/day or 300 mg/day and antidepressant therapy; (3) the fixed-dose combination of olanzapine 6, 12, or 18 mg/day with fluoxetine 50 mg/day; or (4) antidepressant therapy alone. Cost-effectiveness was assessed in terms of the cost per additional responder at 6 weeks, defined as the ratio of the difference in the cost of MDD-related care over 6 weeks versus antidepressant therapy alone to the difference in the number of patients achieving clinical response by 6 weeks. We estimated the model using data from Phase 3 clinical trials of atypical antipsychotics along with other secondary data sources., Results: With antidepressant therapy alone, the estimated clinical response rate at 6 weeks was 30%. Aripiprazole, quetiapine 150 mg/day, quetiapine 300 mg/day, and olanzapine/fluoxetine were estimated to increase clinical response at 6 weeks to 49%, 34%, 38%, and 45%, respectively. Costs of MDD-related care over 6 weeks were estimated to be $192 for antidepressant therapy, $847 for aripiprazole, $541 for quetiapine 150 mg/day, $672 for quetiapine 300 mg/day plus antidepressant therapy, and $791 for olanzapine/fluoxetine. Costs per additional responder (vs antidepressant therapy) over a 6-week period were estimated to be $3447 for aripiprazole, $8725 for quetiapine 150 mg/day, $6000 for quetiapine 300 mg/day, and $3993 for olanzapine/fluoxetine., Conclusions: Atypical antipsychotics substantially increase clinical response at 6 weeks. Cost per additional responder is lower for aripiprazole than for quetiapine or olanzapine/fluoxetine.

Randomized trials for selective and indicated prevention of depression in both mixed-aged and older adult samples, conducted in high-income countries (HICs), show that rates of incident depression can be reduced by 20-25% over 1-2 years through the use of psychoeducational and psychological interventions designed to increase protective factors. Recurrence of major depression can also be substantially reduced through both psychological and psychopharmacological strategies. Additional research is needed, however, to address the specific issues of depression prevention in older adults in low- and middle-income countries (LMICs). The growing number of older adults globally, as well as workforce issues and the expense of interventions, makes it important to develop rational, targeted, and cost-effective risk-reduction strategies. In our opinion, one strategy to address these issues entails the use of lay health counselors (LHCs), a form of task shifting already shown to be effective in the treatment of common mental disorders in LMICs. We suggest in this review that the time is right for research into the translation of depression-prevention strategies for use in LMICs.

Objective: To determine the cost-effectiveness of fluoxetine and cognitive-behavioral therapy (CBT) for major depression in Thailand., Methods: A microsimulation model was developed to describe the variation in course of disease between individuals. Model inputs included Thai data on disease parameters and costs while impact measures were derived from a systematic review and meta-analysis of the international literature. Fluoxetine as the cheapest antidepressant drug in Thailand was analyzed for treatment of episodes plus a 6-month continuation phase and for maintenance treatment over 5 years of follow-up. CBT was analyzed for episodic treatment and for 5-year maintenance treatment. Results are presented as cost (Thai bahts) per disability-adjusted life-year (DALY) averted, compared with a "do-nothing" scenario., Results: The cost-effectiveness ratios of all interventions were below 1 time Thailand's gross domestic product of 110,000 bahts per capita. The uncertainty ranges around the cost-effectiveness ratios overlap: maintenance treatment with CBT 11,000 bahts per DALY (8,000-14,000); episodic treatment with CBT 23,000 bahts per DALY (10,000-36,000); episodic plus continuation drug treatment 33,000 bahts per DALY (26,000-44,000); maintenance drug treatment 38,000 bahts per DALY (30,000-48,000); and episodic drug treatment 42,000 bahts per DALY (32,000-57,000)., Conclusions: CBT and generic fluoxetine are cost-effective treatment options for both episodic and maintenance treatment of major depression in Thailand. Maintenance treatment has the greatest potential of health gain., (Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Newer generation antidepressant drugs, with improvements in safety and tolerability, have replaced tricyclic antidepressants as first-line treatment of depressive illness. However, no single antidepressant drug from any class has distinguished itself as the obvious first-line treatment of major depression. The choice of therapy is driven primarily by patient choice, with informed consent for the risks of adverse effects. Cost has become an additional factor in this decision as several of the newer antidepressant drugs are now available in generic form. Several augmentation and drug-switching strategies have demonstrated benefit in refractory illness. While no single strategy distinguished itself as superior to the others, some have been more rigorously tested. Ongoing efforts at improving effectiveness, time to response, and tolerability have led to novel drug therapies. Efforts at characterizing predictors of treatment outcomes now include pharmacogenetic studies.

Objective: To evaluate the benefit of pharmacogenetics in antidepressant treatment., Methods: In a simulated trial 100,000 subjects in a current episode of major depressive disorder (MDD) received citalopram or bupropion based on the clinician's decision (algorithm A) or following indications from 5-HTTLPR genetic testing (algorithm B), which effect size of was estimated from a meta-analysis of pharmacogenetic trials. A and B were compared in a cost-utility analysis (12 weeks). Costs (international $, 2010) were drawn from official sources. Treatment effects were expressed as quality-adjusted life weeks (QALWs). Outcome was incremental cost-effectiveness ratio (ICER)., Results: Under base-case conditions, genetic test use was associated with increases in antidepressant response (0.062 QALWs) and tolerability (0.016 QALWs) but cost benefit was not acceptable (ICER = $2,890; $1,800-$4,091). However, when the joint effect on antidepressant response and tolerability was analyzed in two recurrent episodes, ICER dropped to $1,392 ($837-$1,982). Cost-effectiveness acceptability curve (CEAC) showed a >80% probability that ICER value fell below the commonly accepted 3 times Gross Domestic Product (GDP) threshold (World Health Organization) and therefore suggesting cost-effectiveness., Conclusion: Notwithstanding some caveats (exclusion of gene-gene and gene-environment interactions; simple 5-HTTLPR architecture), this simulation is favourable to incorporate pharmacogenetic test in antidepressant treatment.

Objective: To compare health care utilization and expenditures in patients with depression whose initial antidepressant (AD) treatment was augmented with a second-generation antipsychotic., Methods: Claims data from January 1, 2001, through June 30, 2009, were used to select patients aged 18 to 64 years with depression treated with ADs augmented with aripiprazole, olanzapine, or quetiapine. Patients were required to have 6 months of continuous eligibility before the first AD prescription and 6 months after the second-generation antipsychotic augmentation (index) date. Utilization and expenditures were assessed for 6 months after the index date. Multivariate regression was used to estimate adjusted expenditures and risks for hospitalizations and emergency department visits., Results: A total of 483 patients treated with aripiprazole, 978 with olanzapine, and 2471 with quetiapine were selected. Mean adjusted expenditures for aripiprazole were significantly lower than those for olanzapine for each service category (all-cause, all-cause medical care, mental health-related, and mental health-related medical care) and were significantly lower than those for quetiapine for each category with the exception of mental health-related. The adjusted risks for hospitalization and emergency department visits were significantly higher for quetiapine than for aripiprazole., Conclusions: Compared with patients treated with ADs and aripiprazole, those treated with ADs and olanzapine or quetiapine had greater utilization and higher expenditures., (Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.)

The aim of this study was to examine the association between duloxetine adherence/persistence and hospital utilization. In a managed care claims database, 8521 patients with a major depressive disorder diagnosis were initiated on duloxetine in 2006. Patients had no active duloxetine prescription for 6 months before initiation and had continuous enrollment for 12 months preinitiation and postinitiation. Adherence was defined as medication possession ratio of 0.8 or more, and persistence was defined as the duration of therapy without exceeding a 30-day gap. Logistic regression and negative binominal regression were conducted. Overall, 55.8% of patients were adherent and the average duration of duloxetine therapy was 118.4 days within 6 months after initiation. Adherent patients had significantly lower rates of hospitalization (19.7 vs. 23.4%, P<0.0001) and emergency room visits (30.6 vs. 36.9%, P<0.0001) than nonadherent patients. Hospitalization and emergency room visits were significantly reduced with treatment persistence (P<0.0001). After adjustment for demographics, comorbidities, and prior hospitalization, adherence was associated with reduced hospitalization (odds ratio=0.86) and emergency room visits (odds ratio=0.80). Patients on duloxetine of more than 90 days, compared with less than 31 days, were 16% less likely to be hospitalized and 22% less likely to have emergency room visits. Duloxetine adherence and persistence appear to be associated with reduced hospital utilization in the 1-year follow-up period., (2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.)