Search

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.)

Context/Objective: Depression is the most common psychological comorbidity associated with spinal cord injury (SCI) and affects healthcare utilization and costs. This study aimed to use an International Classification of Disease (ICD) and prescription drug-based depression phenotypes to classify people with SCI, and to evaluate the prevalence of those phenotypes, associated risk factors, and healthcare utilization. Design: Retrospective Observational Study Setting: Marketscan Database (2000-2019) Participants: Individuals with SCI were classified into six ICD-9/10, and prescription drugs defined phenotypes: Major Depressive Disorder (MDD), Other Depression (OthDep), Antidepressants for Other Psychiatric Conditions (PsychRx), Antidepressants for non-psychiatric condition (NoPsychRx), Other Non-depression Psychiatric conditions only (NonDepPsych), and No Depression (NoDep). Except for the latter, all the other groups were referred to as "depressed phenotypes". Data were screened for 24 months pre- and 24 months post-injury depression. Interventions: None Outcome Measures: Healthcare utilization and payments Results: There were 9,291 patients with SCI classified as follows: 16% MDD, 11% OthDep, 13% PsychRx, 13% NonPsychRx, 14% NonDepPsych, 33% NoDep. Compared with the NoDep group, the MDD group was younger (54 vs. 57 years old), predominantly female (55% vs. 42%), with Medicaid coverage (42% vs. 12%), had increased comorbidities (69% vs. 54%), had fewer traumatic injuries (51% vs. 54%) and had higher chronic 12-month pre-SCI opioid use (19% vs. 9%) (all P  < 0.0001). Classification into a depressed phenotype before SCI was found to be significantly associated with depression phenotype post-SCI, as evidenced by those who experienced a negative change (37%) vs. a positive change (15%, P  < 0.0001). Patients in the MDD cohort had higher healthcare utilization and associated payments at 12 and 24 months after SCI. Conclusion: Increasing awareness of psychiatric history and MDD risk factors may improve identifying and managing higher-risk patients with SCI, ultimately optimizing their post-injury healthcare utilization and cost. This method of classifying depression phenotypes provides a simple and practical way to obtain this information by screening through pre-injury medical records.

Introduction: Bipolar disorder is a recurrent mental health disorder with a prevalence rate of 1.4%. On average, there can be a delay of 9.5 years from the initial presentation of symptoms to a confirmed diagnosis. Individuals living with bipolar disorder have a reduced life expectancy. There is limited evidence regarding the effectiveness of antidepressants in treating bipolar disorder. The ASCEnD clinical trial will test the clinical and cost-effectiveness of the aripiprazole/sertraline combination in comparison with quetiapine for the treatment of bipolar depression (individuals who suffer from depressive episodes in bipolar disorder) and will include a nested qualitative study., Methods: The qualitative study will use semi-structured interviews to explore pilot trial participants' and clinicians' perspectives on recruitment procedures, the acceptability of the intervention, the management of bipolar disorder and attitudes to medication combinations., Conclusion: Findings will inform recruitment strategies and optimise training for the participating sites in the ASCEnD full trial. They will also help to illuminate the lived experience of people with bipolar disorder and the clinicians who work with people with bipolar disorder. The discussion will explore perspectives on the delay in diagnosis, having a diagnosis, the impact of living with bipolar disorder and attitudes to treatment, including drug combinations., Patient or Public Contribution: A Lived Experience Advisory Panel (LEAP) has been convened with the support of the McPin Foundation, which will contribute to the ASCEnD trial and its nested qualitative study to provide input on the design and delivery of the trial and qualitative study, analysis of qualitative data and dissemination of findings., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

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.)

Background: The prevalence of depression is gradually increasing worldwide with an increasing utilization of antidepressants. Nevertheless, despite their lower costs, generic-brand antidepressants were reported to be less prescribed. We aimed to examine the costs of reference- versus generic-brand antidepressant prescriptions in primary care practice., Methods: This cross-sectional study included electronic prescriptions for adult patients that contained antidepressants (World Health Organization's Anatomical Therapeutic Chemical (ATC) code: N06A), which were generated by a systematically selected sample of primary care doctors ( n = 1431) in Istanbul in 2016. We examined the drug groups preferred, the reference- versus generic-brand status, and pharmacotherapy costs., Findings: The majority of the prescriptions were prescribed for women (71.8%), and the average age of the patients was 53.6 ± 16.2 years. In prescriptions with a depression-related indication ( n = 40 497), the mean number and cost of drugs were 1.5 ± 1.0 and 22.7 ± 26.4 United States Dollar ($) per prescription, respectively. In these prescriptions, the mean number and cost of antidepressants per encounter were 1.1 ± 0.2 and $17.0 ± 13.2, respectively. Reference-brand antidepressants were preferred in 58.2% of depression-related prescriptions, where the mean cost per prescription was $18.3 ± 12.4. The mean cost per prescription of the generics, which constituted 41.8% of the antidepressants in prescriptions, was $15.1 ± 11.4. We found that if the generic version with the lowest cost was prescribed instead of the reference-brand, the mean cost per prescription would be $12.9 ± 11.2., Conclusions: Our study highlighted the substantial pharmacoeconomic impact of generic-brand antidepressant prescribing, whose preference over reference-brands could reduce the cost of antidepressant medication treatment by 17.5% in primary care, which could be approximately doubled if the cheapest generic antidepressant had been prescribed.

In France, the funding of mental health institutions relies on an annual budget allocation. Esketamine, a non-competitive NMDA glutamate receptor antagonist, has been approved for adults with treatment-resistant major depressive disorder since 2019. However, due to its high cost (€200 per 28 mg device, excluding tax), the aim of this work was to evaluate whether the income received by an institution for the management of a patient treated with Esketamine could cover the purchase of devices, based on real clinical data. Within our institution, seven patients underwent treatment with Esketamine during the study period resulting in a total usage of 714 devices, amounting to a purchase cost of €142,800. Over the course of the follow-up period, the institution received €149,054 in revenue for the treatment of these patients. Our analysis reveals that the expense associated with Esketamine constitutes 95.8 % of the income generated from caring for these patients. This not only raises questions about the pricing of this drug but also highlights the lack of a funding system for costly psychiatric drugs. This concern extends to somatic treatments associated with psychiatric care., (Copyright © 2023 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

The social restrictions amid coronavirus disease 2019 (COVID-19) pandemic have posed a serious threat to mental health and have implications in the use of medications for mental health including antidepressants (ADs). This study investigated the trends in prescriptions and costs of various ADs in England during COVID-19 pandemic. National prescribing rates and net ingredient costs (NIC) of all ADs prescriptions during 2016 to 2020 were analyed. The total number of ADs prescriptions dispensed during COVID-19 pandemic (January to December 2020) were 78 million, 4 million more than in 2019 that costed NHS England £ 139 million more than in 2019. Sertraline, an SSRI antidepressant drug, alone accounted for an extra £113 million during 2020 than in 2019. The peak dispensing for ADs was observed in March 2020 while the total costs for AD drugs peaked in April 2020. The rising prescription costs for ADs during COVID-19 pandemic is a potential cause of concern, in particular the increasing use in adolescents and younger adults needs attention, who are at a higher risk of life-threatening adverse drug reactions.

Background: SSRIs and SNRIs are antidepressants that have largely substituted old antidepressants like Monoamine Oxidase Inhibitors (MAOIs) and Tricyclic Antidepressants (TCAs). They have been widely used since 1987 when the FDA approved the first SSRI Fluoxetine and the first SNRI Venlafaxine in 1993. Since then, several new SSRIs and SNRIs have been approved and entered the market. Utilization, pricing, and spending trends of SSRIs and SNRIs have not been analyzed yet in Medicaid., Aim: To assess the trends of drug expenditure, utilization, and price of SSRI and SNRI antidepressants in the US Medicaid program, and to highlight the market share of SSRIs and SNRIs and the effect of generic drug entry on Medicaid drug expenditure., Methods: A retrospective descriptive data analysis was conducted for this study. National pharmacy summary data for study brand and generic drugs were retrieved from the Medicaid State Outpatient Drug Utilization Data. These data were collected by the US Centers for Medicare and Medicaid Services (CMS). The study period was between 1991 and 2018. Study drugs include 12 different SSRI and SNRI brands and their generics available in the market, such as citalopram, escitalopram, paroxetine, fluoxetine, sertraline, venlafaxine, desvenlafaxine, duloxetine, and levomilnacipran. Data were analyzed annually and categorized by total prescriptions (utilization), total reimbursement (spending), and cost per prescription as the proxy of the price for each drug., Results: From 1991 to 2018, total prescriptions of SSRI and SNRI drugs rose by 3001%. Total Medicaid spending on SSRIs and SNRIs increased from USD 64.5 million to USD 2 billion in 2004, then decreased steadily until it reached USD 755 million in 2018. The SSRIs average utilization market share was 87% compared to 13% of the SNRIs utilization market share. About 72% of total Medicaid spending on the two groups goes to SSRIs, while the remaining 28% goes to SNRIs. Brand SSRIs and SNRIs prices increased over time. On the contrary, generic drugs prices steadily decreased over time., Discussion: An increase in utilization and spending for both SSRI and SNRI drugs was observed. After each generic drug entered the market, utilization shifted from the brand name to the respective generic due to their lower price. These generic substitutions demonstrate a meaningful cost-containment policy for Medicaid programs., Implications for Health Policies: Our findings show the overall view of Medicaid expenditure on one of the most commonly prescribed drug classes in the US. They also provide an important insight toward the antidepressant market and the importance of monitoring different drugs and their alternatives.

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.

Introduction: Major depressive disorder (MDD) is a globally prevalent chronic psychiatric illness with a significant disease impact. As many as 30% of patients with MDD do not adequately respond to two therapies and are considered to be treatment resistant. This study aimed to quantify healthcare costs associated with treatment resistant depression (TRD) in the UK., Methods: A retrospective chart review of patients with TRD was conducted in primary and secondary care settings over a 2 year period. Data abstracted from medical records of patients included demographics, clinical characteristics and healthcare resource utilization (HCRU; number of consultations, use of Crisis Resolution and Home Treatment Teams [CRHTTs], non-drug and drug interventions, and hospitalizations). HCRU per patient per month (28 days) was calculated for three health states: major depressive episode (MDE), remission and recovery. Unit costs were from the British National Formulary (BNF) and the Personal Social Services Research Unit (PSSRU)., Results: A total of 295 patients with TRD were recruited between January 2016 and May 2018. The mean age of the total sample was 43.3 years; 60.3% were female. Costs per patient, per 28 days, were highest in the MDE state, with the average cost (£992) mainly driven by consultations, non-drug treatment, hospitalizations and CRHTT, with a considerable fall in costs as patients moved into remission and subsequent recovery., Conclusion: The results suggest that antidepressant treatments for TRD that are more effective in reducing the time spent in an MDE health state, and helping patients achieve remission and recovery, are essential for reducing the overall HCRU and costs in patients with TRD. Cost of TRD in the UK Strengths and limitations of this study This observational study of TRD is the first to assess the HCRU impact associated with different predefined health states. Using retrospective data from both primary and secondary care physicians from regions across the UK ensures a representative real-world patient population. One limitation is that the selection of patients is based on criteria that define TRD that rely on physician judgement. Although the study captures direct HCRU costs, the indirect costs of lost productivity and care are not included in the overall burden. This study has defined the current clinical management of patients with TRD in the UK and provides an estimate of the associated HCRU and associated costs.

Objectives: The Depression Care for People with Cancer program (DCPC) is a cost-effective depression care model for UK patients with cancer. However, DCPC's cost-effectiveness in the United States is unknown, particularly for patients with prostate cancer in the United States. This study evaluates the health and economic impact of providing DCPC to patients with prostate cancer., Methods: DCPC was compared with usual care in a mathematical model that simulates depression and its outcomes in a hypothetical cohort of US patients with prostate cancer. DCPC was modeled as a sequential combination of universal depression screening, post-screening evaluations, and first-line combination therapy. Primary outcomes were lifetime direct costs of depression care, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Secondary outcomes included life expectancy, number of depression-free months and lifetime depressive episodes, duration of depressive episodes, cumulative incidence of depression, lifetime depression diagnoses/misdiagnoses, and the cumulative incidence of maintenance therapy for depression. Sensitivity analyses were used to examine uncertainty., Results: In the base case, DCPC dominated usual care by offering 0.11 more QALYs for $2500 less per patient (from averted misdiagnoses). DCPC also offered 5 extra depression-free months, shorter depressive episodes, and a lower chance of maintenance therapy. DCPC's trade-offs were a higher cumulative incidence of depression and more lifetime depressive episodes. Life expectancy was identical under usual care and DCPC. Sensitivity analyses indicate that DCPC was almost always preferable to usual care., Conclusion: Compared with usual care, DCPC may offer more value to US patients with prostate cancer. DCPC should be considered for inclusion in prostate cancer survivorship care guidelines., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: We compared economic outcomes when elderly patients with neuropsychiatric disorders received psychotropic medications guided by a combinatorial pharmacogenomic (PGx) test., Methods: This is a subanalysis of a 1-year prospective assessment of medication cost for patients with neuropsychiatric disorders receiving combinatorial PGx testing. Pharmacy claims were used to compare per member per year (PMPY) medication cost for patients ≥65 and <65 years old when medications were congruent or incongruent with the PGx test. Polypharmacy was also assessed., Results: Congruent prescribing was associated with savings of US$3497 PMPY ( P < .001) for patients ≥65 years and US$2467 PMPY ( P < .001) for patients <65, compared to incongruent prescribing. Congruent prescribing in patients ≥65 treated by primary care providers was associated with US$4113 PMPY ( P = .026) in savings, while congruent prescribing by psychiatrists was associated with US$120 PMPY ( P = .719). Congruent prescribing was also associated with one fewer neuropsychiatric medication for patients ≥65 ( P = .070)., Conclusion: Congruence with PGx testing was associated with medication cost savings in elderly patients.

Background and objective : Depression is a global public health threat, and its treatment constitutes drugs in psychopharmacology, a domain that is rapidly growing with the addition of newer agents in market that are of high cost. Therefore, the present study aims to investigate the number of registered brands and price variation of oral antidepressants in Pakistan. Methods : A descriptive observational study was carried out to analyze the cost of oral antidepressants in Pakistan. Pharma guide 2019 was used to derive the cost of antidepressants marketed in Pakistan. The details about the number of registered brands and maximum and minimum prices of antidepressant drugs were calculated. Results : Sixteen drugs in 38 formulations were registered in 607 brands in Pakistan. Variations among 38 different formulations range from 0% to 746.39%. Out of these 38 formulations, 31 had variations below 200%, while 7 formulations had price variation above 200%. The highest price (746.39%) variation was observed for citalopram 20 mg (price per tablet PKR 6.79 to PKR 57.47) and no (0%) price variation was for bupropion 75 mg (price per tablet PKR 10). Conclusion : The study revealed wide variations in the number of registered brands and prices of oral tablets of antidepressants in Pakistan. The government needs to devise effective strategies to implement established policies to ensure uniformity in price, quality, and effectiveness with the ultimate goal to reduce treatment cost. Also, measures should be taken to inform prescribers about cost variation of drugs as prerequisite for cost-effective treatments to ultimately reduce treatment cost and financial burden and improve patient's adherence to therapy.

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.

Clinical guidelines for depression management recommend continuous antidepressant medication; however, poor adherence to medication is commonly seen in the treatment of depression. Income is an important factor influencing antidepressant medication adherence. The purpose of this study was to investigate the relationship between income level and adherence to antidepressant medication in outpatients with depression. This was a retrospective cohort study using National Health Insurance claim data for services provided between January 1 and December 31, 2012. We examined data from a total of 142,336 individuals aged 18 years or older who were continuously enrolled in treatment after a new episode of major depression and who had initiated antidepressant treatment. The operational definition of adherence to antidepressant treatment was medication being dispensed to the patient at least 80% of the time during 3 and 6 months (ie. MPR ≥80%). To investigate the relationship between income level and adherence to antidepressants, we estimated adjusted odds ratios and 95% confidence intervals using hierarchical logistic regression analysis, adjusting for sociodemographic, clinical, and medical use characteristics. A total of 22.64% and 15.13% of depression patients showed adherence to antidepressants during 3 and 6 months, respectively. A statistically significant association was found between income level and adherence to antidepressants over 3 and 6 months for individuals with employee and self-employed subscribers. In addition, adherence to antidepressants was lower among those with a lower income than those with a higher income. We confirmed that social disparities exist in adherence to antidepressant treatment by income level in this Korean population-based retrospective cohort of depression outpatients., Competing Interests: The authors have declared that no competing interests exist.

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.)

Purpose: Antidepressant augmentation strategies for treatment-resistant depression (TRD) are discussed here with an analysis of patient out-of-pocket costs for various medications. The choice of agent ranges from newer atypical antipsychotics (aripiprazole, brexpiprazole, quetiapine) to older agents including buspirone, liothyronine (T3), and lithium. We sought to better understand the differences among these agents to aid in clinical decision making., Methods: We conducted a focused review of the support for each of the aforementioned agents in antidepressant augmentation. We then compared the approximate out-of-pocket cost for each medication during a typical augmentation trial using the typical prescription costs on ClinCalc.com derived from the Medical Expenditure Panel Survey. We calculated the cost to achieve response for one patient with TRD based on the number needed to treat (NNT)., Findings: We observed significant variance in cost to achieve response based on the NNT derived from our review of each of the medications. For example, the overall out-of-pocket cost for one patient to achieve response with aripiprazole (the costliest generic agent) could cover lithium prescriptions for 4 to 5 patients with TRD to achieve response. Although brexpiprazole was estimated separately because of its brand name cost, we estimated that 324 patients receiving lithium could achieve response for same cost of single patient receiving brexpiprazole., Implications: These findings suggest that among augmentation agents, there are differences in cost that may be highly important in clinical decision making. Other issues of medication monitoring may incur additional costs, and brand name medications offer significantly greater complexity and potential out-of-pocket costs to patients. The use of lithium as a first-line agent for TRD should be considered based on low cost, lowest NNT, and data in support of its efficacy.

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.

Objective: The number of prescriptions for antidepressants (ADs) in England and Wales has almost doubled in the past decade. The objective of this article is to describe the current prescribing rates of different antidepressants by general practice (GP) practice., Methods: We collated the prescribing behavior in each GP practice in the year April 1, 2017, to March 31, 2018. The monthly GP practice prescribing data reports for medication prescribing for each British National Formulary code and practice, as well as the prescriptions, quantity, and costs were examined in relation to prescribing practice., Results: The data showed that 2.1 billion doses of antidepressant were prescribed to a total population of 52 million people. That equates to 11% of individuals taking ≥ 1 antidepressants on any day. Selective serotonin reuptake inhibitors (SSRIs) were the most prescribed class of ADs, with sertraline the most prescribed SSRI. The other most prescribed ADs were citalopram, fluoxetine, and mirtazapine. Some older agents, such as trimipramine and doxepin, are prescribed at a very high tariff., Conclusions: Broadly, the findings are in keeping with National Institute for Health and Care Excellence guidance in that the bulk of prescriptions were for SSRIs. Regular audit of patient treatment at a general practice level will ensure appropriate targeted use of licensed medications as supported by the evidence base., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

Background: The incidence and burden of depressive disorders are increasing in South Korea. There are many differences between pharmaceutically treated depression (PTD) and treatment-resistant depression (TRD), including the economic consequences; however, to our knowledge, the economic burden of depression is understudied in South Korea. Therefore, the objective of the present study was to calculate the different economic costs of PTD and TRD in South Korea, specifically by comparing several aspects of medical care., Methods: This study comprised patients aged 18 and over who were newly prescribed antidepressants for more than 28 days with a depression code included from January 1, 2012, to December 31, 2012, by the Health Insurance Review and Assessment Service (HIRA). TRD was classified as more than two antidepressant regimen failures in PTD patients. The cost was calculated based on the cost reflected on the receipt registered with HIRA., Results: Of the 834,694 patients with PTD, 34,812 patients (4.17%) were converted to TRD. The cost of medical care for TRD (6,610,487 KRW, 5881 USD) was approximately 5 times higher than the cost of non-TRD (1,273,045 KRW, 1133 USD) and was significantly higher for patients with or without depression and suicide codes. Medical expenses incurred by non-psychiatrists were roughly 1.7 times higher than those incurred by psychiatrists., Conclusions: TRD patients had significantly higher healthcare costs than PTD patients. Identifying these financial aspects of care for depression can help to establish a more effective policy to reduce the burden on mentally ill patients.

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

Background: Prescription of antidepressant drugs (ADs) has increased in recent decades, with rising costs for patients as well as for the health care system. There is sparse evidence of which factors explain the high economic costs and financial burden for the general population., Aims of the Study: The aim was to assess individual-level determinants of out-of-pocket and total health care costs of AD use in the Swedish general population., Methods: We randomly sampled 400,000 individuals aged 18+ from Statistics Sweden's population register from 2010 to 2013. Two-part regression models were used for our two primary outcome variables: (i) total health care costs for AD use per year and individual, and (ii) total out-of-pocket costs of AD use per year and individual., Results: Women, the unemployed, unmarried people and residents of big cities have both higher use of ADs and higher associated total health care and out-of-pocket costs. Today, ADs are relatively inexpensive and average cost differences among all groups are therefore minor. The elderly have higher use of ADs, but are more commonly low-volume users and do not have higher total health care or out-of-pocket costs., Discussion and Limitations: Groups with relatively low socioeconomic status are at risk of higher costs for antidepressant use. However, given the Swedish system of drug subsidies, differences in financial burden for individuals are minor. The limitations of this study included that we lacked data on diagnosis and could therefore not categorize the reasons for AD consumption. Furthermore, our results may not be generalized to other countries with a lower AD prevalence then Sweden's, since our estimates are dependent on the point prevalence of antidepressant use in the population., Implications for Health Care Provision and Use: Groups with higher AD consumption and economic costs may suffer from more severe depression owing to more risk factors and less social support in their surroundings, and may be in greater need of additional treatment and support than other groups., Implications for Health Policies and Further Research: Our results offer insight at an aggregate level, and more information on the underlying causes of higher costs is needed to discern the policy implications.

Objective: To describe the prevalence and costs of anxiety and depression among moderate-to-severe psoriasis (PsO) patients in a commercially-insured US population. Methods: The IBM MarketScan Commercial database was used to select adults with moderate-to-severe PsO (≥1 PsO diagnosis and ≥1 systemic or biologic medication) within each calendar year from 2014 to 2016. Adults with no diagnosis of PsO or similar disorders were randomly selected (2014-2016) and matched 1:1 to PsO patients to compare the prevalence of anxiety and depression each year. Moderate-to-severe PsO patients identified in 2014 with continuous enrollment through 2015 were stratified into those with treated anxiety and/or depression (≥1 anxiety or depression diagnosis plus any anxiolytics, antidepressants, or antipsychotics within 30 days) vs those without anxiety/depression, and then matched 1:1 to determine the incremental burden of treated anxiety/depression among PsO patients. All-cause and PsO-related healthcare costs were compared between the matched cohorts using generalized linear models. Results: In total, 69,644 matched PsO and non-PsO patients were identified in 2014, 61,478 in 2015, and 66,880 in 2016. The prevalence of anxiety/depression among PsO patients increased more than for matched controls, from 18.2% vs 12.2% in 2014 ( p  < 0.01) to 19.6% vs 13.1% in 2016 ( p  < 0.01). Prevalence of treated anxiety/depression followed the same trend, with increases from 14.5% vs 8.9% in 2014 ( p  < 0.01) to 15.9% vs 9.9% in 2016 ( p  < 0.01). For patients with moderate-to-severe PsO, unadjusted incremental all-cause healthcare costs associated with treated anxiety/depression were $8,077 ( p  < 0.01); 91% was due to utilization of medical services such as hospitalizations, ER visits, office visits, and other outpatient services (all p  < 0.01). Conclusions: The prevalence of psychiatric disorders is higher among PsO patients than the general population, and the incremental burden of treated anxiety/depression is substantial. Further research is needed, but PsO treatments that improve psychiatric symptoms such as anxiety/depression may benefit patients and reduce their economic burden.

Background: Depressed patients often focus on negative life events. Effective antidepressant therapy reverses this negative emotional bias (NEB) within 1 week. Clinical therapeutic effect usually requires 4-6 weeks. The value of implementing NEB monitoring for the personalisation of antidepressant therapy is unknown., Objective: To estimate the likely outcome and cost consequences of adopting the P1vital Oxford Emotional Test Battery (ETB) for this purpose in routine primary care in England., Methods: A hybrid decision analytic model (decision tree plus Markov model) was developed to estimate the cost-effectiveness of ETB monitoring versus no ETB over 52 weeks using quality-adjusted life years (QALYs). Differences in depression severity, episode type and analytical perspectives were considered. Input data were derived from relevant guidelines, literature, national databases, expert opinion and the developers for the year 2013. Multiple sensitivity analyses addressed uncertainty., Findings: The mean number of ETB tests is 2.162 per newly diagnosed patient and 2.166 per patient with recurrent depression. The incremental cost-effectiveness of ETB versus 'no ETB' is £4355/QALY from the healthcare perspective. From the broader societal perspective, ETB is more effective and cost saving., Conclusions: Monitoring negative emotional bias in primary care in England for personalised antidepressant treatment using ETB seems as an effective and cost-effective option under all considered scenarios (including worst case). Its main economic value seems to lie in reduced productivity loss as opposed to healthcare savings., Clinical Implications: The test supports accelerated application of evidence-based depression care. Further optimisation and implementation in the ongoing European PReDicT trial is ongoing., Competing Interests: Competing interests: GRD, JK and CTD own shares in P1vital Products Ltd. JK is an employee of P1vital Products Ltd. GRD, CTD, GMG and CJH own shares in P1vital Ltd. GRD and CTD are employees of P1vital Ltd., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Clinicians play an important role in containing pharmaceutical spending at the patient level, as well as ensuring efficacy and quality outcomes, yet little research has examined how to achieve this goal., Measures: Using auditing and feedback (A&F) as part of a Pharmacy and Therapeutics (P&T) Committee, we evaluated our community-based hospice program's prescribing habits for opioids, antipsychotics, and antidepressants and calculated oral pharmaceutical prescription costs per-patient-day. Quality of care was reflected by patient pain scores in electronic medical records., Intervention: Our P&T Committee adopted an A&F approach to monitor and assess provider prescribing habits and cost. An already-existing pain quality improvement program assessed care quality., Outcomes: Pain relief either improved or was maintained while medication costs were reduced by over $1.00 per-patient-day from 2010 to 2011., Conclusions/lessons Learned: An active, hospice P&T Committee featuring A&F can significantly affect medication costs for a hospice program while maintaining or improving patient outcomes., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Treatment-resistant depression (TRD), defined as episodes of depression that do not respond to ≥ 2 lines of adequate depression therapy, is associated with a high economic burden. Although the economic burden of TRD is reported elsewhere, its exact magnitude and current value is uncertain due to differences in methodology in TRD identification., Objective: To compare all-cause health care resource utilization (HCRU) and associated health care payments among patients with TRD and those with depression but without TRD, using administrative claims data., Methods: This retrospective cohort study used data from the Truven Health MarketScan Commercial and Medicare Supplemental Databases (October 1, 2008-September 30, 2016). All patients were aged ≥ 18 years, newly diagnosed with depression (≥ 1 inpatient admission or ≥ 2 outpatient visits with a primary or secondary depression diagnosis), and newly treated with depression therapy. The population included patients with and without TRD. Patients with TRD were defined as having been treated with ≥ 3 courses of depression therapy within a 360-day period (initiation of the third course served as the TRD index date), while patients without TRD (non-TRD) were defined as having been treated with 2 courses of depression therapy. TRD and non-TRD cohorts were matched using propensity scores. Using the TRD index date of their matched TRD pair, non-TRD patients were assigned a simulated index date following second-line therapy. Eligible TRD and non-TRD patients were continuously enrolled from a 12-month baseline period before the first course of therapy through a 12-month follow-up period beginning with the TRD index date and simulated index date, respectively. Annual all-cause HCRU and associated payments (2016 U.S. dollars) were assessed in aggregate and by place of service during the follow-up period and were compared between the matched cohorts using nonparametric Wilcoxon signed-rank tests., Results: The matched analysis included 800 patients in each cohort. For both cohorts, the mean age of patients was 39 years, and 60% were female. All clinical characteristics and all-cause HCRU were comparable at baseline. Compared with non-TRD patients, TRD patients had a significantly higher mean number of all-cause emergency department (ED) visits (0.29 vs. 0.24), outpatient visits (18.0 vs. 13.4), and prescriptions (30.0 vs. 24.0; all P < 0.05) during the 12-month follow-up period. The TRD cohort also had significantly higher mean total all-cause health care payments ($9,890 vs. $6,848; P < 0.001) and mean payments by place of service (ED: $518 vs. $408; outpatient: $3,603 vs. $2,585; pharmacy: $2,613 vs. $1,837; all P < 0.05) compared with the non-TRD cohort., Conclusions: In relation to propensity score-matched non-TRD patients, TRD patients used significantly more resources (ED visits, outpatient visits, and number of prescriptions) and had significantly higher overall health care payments. These results serve to highlight the unmet need in patients with TRD, suggesting that improved and more effective management of these patients may help reduce the economic burden of disease., Disclosures: This study was funded by Alkermes. Sussman and Menzin, employees of Boston Health Economics, were paid consultants, and Olfson, an employee of Columbia University Irving Medical Center, was an unpaid consultant to Alkermes in connection with the study and development of this research article. O'Sullivan and Shah are employees of the study sponsor. Results from this analysis were first presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting in Boston, MA, on April 23-26, 2018.

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.

Aim: Previous studies indicate that mirtazapine is unique in its quick responsiveness compared to other antidepressants. Although some other studies have evaluated its cost-effectiveness, they have not considered its early stage remission rate. The aim of this study was to address this research gap by using precise clinical data to evaluate the cost-effectiveness of mirtazapine in Japan., Methods: We developed a Markov model to reflect the week-by-week transition probabilities. The Markov cycle was set as 1 week. While our clinical parameters were obtained largely from existing meta-analyses, cost data were derived from government reports. Cost-effectiveness was evaluated by incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year estimated based on the probability sensitivity analyses. The ICERs were estimated at 2, 8, 26, and 52 weeks., Results: In severe depression, the ICERs ranged between JPY 872 153 and 1 772 723. The probability of mirtazapine being cost-effective ranged from 0.75 to 0.99 when the ICER threshold was JPY 5 000 000. In moderate depression, the ICERs ranged between JPY 2 356 499 and 4 770 145. The probability of mirtazapine being cost-effective ranged from 0.55 to 0.83 when the ICER threshold was JPY 5 000 000., Conclusion: When considering the early stage efficacy of mirtazapine, it appeared to be cost-effective compared to selective serotonin reuptake inhibitors, especially for severe depression and in the early stage treatment in the Japanese setting. However, our study has some limitations. First, mirtazapine is compared with batched selective serotonin reuptake inhibitors rather than individual ones. Second, we did not consider antidepressant combination therapy as treatment options., (© 2019 The Authors. Psychiatry and Clinical Neurosciences © 2019 Japanese Society of Psychiatry and Neurology.)

This study aimed to assess the associations between the use of different types of antidepressants and health service utilization and costs among depressed patients. Data used in this study were retrieved from the Taiwan National Health Insurance Research Database. We identified 447 411 new antidepressant users during the study period (2011-2015) and they were individually followed for a 1-year period. Two-part generalized estimating equation models were conducted. Results demonstrated that there was a substantial decrease in outpatient service utilized by patients undertaking serotonin antagonists and reuptake inhibitors (β = -0.2074), serotonin-norepinephrine reuptake inhibitors (β = -0.0452), tricyclic antidepressants (β = -0.1308), or other antidepressants (β = -0.0637), compared with their counterparts in the selective serotonin reuptake inhibitors group (all P < 0.05). Compared with patients who were treated with selective serotonin reuptake inhibitors, those who were prescribed serotonin antagonists and reuptake inhibitors (β = -0.4934, P < 0.05) or tricyclic antidepressants (β = -0.4194, P < 0.05) had incurred lower costs pertaining to outpatient service, while considerably higher costs were borne by those patients embarked on the treatment of serotonin-norepinephrine reuptake inhibitors (β = 0.3228, P < 0.05) or other antidepressants (β = 0.1118, P < 0.05). We concluded that the initiation of various classes of antidepressants led to significant variations in health service utilization and costs among depressed patients.

Background: Antidepressants, benzodiazapines, and opioid medications are used to manage the pain, anxiety, or depression associated with workplace injuries., Objective: To evaluate the impact of these medications on workers' compensation costs and time lost from work., Methods: A cohort of 22,383 indemnity claims from 2008 to 2013 were evaluated for the association of prescribed medications on claim cost and delayed claim closure controlling for confounders., Results: Claims with anti-depressant, opioid, or benzodiazepine prescriptions were 2.24 (95% CI: 2.00 to 2.51), 1.14 (95% CI: 1.02 to 1.27), and 1.38 (95% CI: 1.23 to 1.54) times more likely to remain open at the end of the study., Conclusion: The concurrent treatment of pain, depression or anxiety, and occupational injuries are associated with large increases in claim cost and delayed return to work.

Background: The estimated effect of unemployment on depression may be biased by time-varying, intermediate, and time-constant confounding. One of the few methods that can account for these sources of bias is the parametric g-formula, but until now this method has required that all relevant confounders be measured., Methods: We combine the g-formula with methods to adjust for unmeasured time-constant confounding. We use this method to estimate how antidepressant purchasing is affected by a hypothetical intervention that provides employment to the unemployed. The analyses are based on an 11% random sample of the Finnish population who were 30-35 years of age in 1995 (n = 49,753) and followed until 2012. We compare estimates that adjust for measured baseline confounders and time-varying socioeconomic covariates (confounders and mediators) with estimates that also include individual-level fixed-effect intercepts., Results: In the empirical data, around 10% of person-years are unemployed. Setting these person-years to employed, the g-formula without individual intercepts found a 5% (95% confidence interval [CI] = 2.5%, 7.4%) reduction in antidepressant purchasing at the population level. However, when also adjusting for individual intercepts, we find no association (-0.1%; 95% CI = -1.8%, 1.5%)., Conclusions: The results indicate that the relationship between unemployment and antidepressants is confounded by residual time-constant confounding (selection). However, restrictions on the effective sample when using individual intercepts can compromise the validity of the results. Overall our approach highlights the potential importance of adjusting for unobserved time-constant confounding in epidemiologic studies and demonstrates one way that this can be done.

Background: We aimed at describing the trends in antidepressants use (AD) by age and sex, during 2007-2011, in 5 European settings (Sweden, Norway, Denmark, Catalonia and Veneto), and to assess whether the differences found across settings could be related to economic, social and cultural determinants., Methods: We collected data of AD use expressed in defined daily doses (DDD). Data were retrieved from population-based databases. We calculated DDD/1000 inhabitants/day. We analysed which economic, social, and cultural covariates determined between-settings differences in AD consumption., Results: The use of AD showed an increasing trend during the study period, being Selective Serotonin Reuptake Inhibitors the most consumed, followed "others AD". Women and the elderly showed the highest AD consumption. Between-settings variability in AD consumption showed a positive correlation with pharmaceutical expenditure and a negative one with general practitioner's rate. After adjusting by pharmaceutical expenditure and general practitioners rate Masculinity, Long-Term Orientation and Individualism cultural dimensions were associated with AD use by using the Hofstede´s cultural dimensions model., Limitations: This study has been conducted in administrative databases, with no information on AD use by indication; differences among AD use could be related to their prescription for other disorders. Analyses were based on a small dataset and none of the results reached statistical significance., Conclusions: AD use increased through 2007-2011. Pharmaceutical expenditure and General Practitioners rate, Masculinity, Long-Term Orientation and Individualism explained the differences in AD use between countries. People's attitude should be considered when designing national campaigns to improve antidepressant use., (Copyright © 2019. Published by Elsevier B.V.)

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 and Objective: Chronic pain is a highly prevalent problem, involving high costs and seriously affecting a patient's quality of life. This review aimed to systematically review economic evaluations of pharmacological-based treatments for non-malignant chronic pain and to compare different treatment approaches with regard to their economic profile., Methods: PubMed and Scopus were systematically searched in April 2016. Studies were included if quality-adjusted life years and incremental cost-effectiveness ratios were reported. Quality assessment was carried out by using La Torre's weighted scale on the Drummond checklist. Costs were converted into US$2014., Results: Fourteen economic evaluations met the inclusion criteria. Three treatment categories identified were: opioids, anticonvulsants, and anti-depressants. Compared to anticonvulsants and antidepressant, opioids had lower ICER. Transdermal buprenorphine showed an ICER of about US$11,000.00 while pregabalin showed an ICER of US$19,200. Studies included showed a diversity of methodological approaches, such as different modeling approaches and different perspectives (NHS and private payer)., Conclusion: There are limitations to the success of making appropriate recommendations about which treatment is most cost-effective due to considerable variability between treatments, pain syndromes, and drug dosages. Opioids may have lower ICER, but the societal implications of the opioid epidemic and overdose deaths should be taken into account when coming to general conclusions about their cost-effectiveness. To ensure correct resource allocation as well as the best benefit for patients, uniform and standardized approaches of cost and outcome measurement in economic evaluations of chronic are needed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Migraine is a common and disabling neurological disease associated with substantial economic burden. Among patients with migraine, it is unknown if cost differences exist when preventive migraine medication (PMM) switches occur., Objective: To understand the cost burden and health care resource utilization of patients who discontinue or cycle through 1 (PMM1), 2 (PMM2), or ≥ 3 (PMM3) unique PMM drug classes over a 12-month period versus patients who adhere persistently to their initial PMM class., Methods: This retrospective observational study used the Truven Health Analytics MarketScan databases to identify adult patients with migraine initiating their first PMM class (antidepressants, antiepileptics, beta blockers, or neurotoxins) from 2011-2013 (index date = first PMM claim). Patients were required to have ≥ 2 outpatient (1 if inpatient) migraine diagnosis codes (ICD-9-CM 346.xx) from 1 year pre-index to 1 year post-index with ≥ 1 code occurring pre-index. Inclusion criteria also required 12 months of pre- and post-index continuous medical and prescription enrollment. All-cause and migraine-specific total direct costs (outpatient, inpatient, emergency department, and prescriptions), based on the 2014 Consumer Price Index, were estimated for each PMM versus a persistent subgroup during the 12-month post-index period. Propensity score bin bootstrapping, controlling for patient baseline characteristics, was used to adjust separate cost comparisons between each PMM subgroup and the persistent subgroup; bootstrap simulations yielded propensity score-adjusted P values., Results: The study population included 55,402 patients who received a PMM. The study population was mainly female (85%) with a mean age of 39.2 years and mean Charlson Comorbidity Index of 0.31. Antiepileptics were the most common drug class chosen at index across all subgroups; however, lower use of antiepileptics was observed in PMM2 and PMM3 subgroups, which were more likely to be prescribed either antidepressants or beta blockers at index. Mean all-cause total direct costs, including prescription costs, were significantly higher in PMM2 ($13,429) and PMM3 ($18,394) subgroups versus the persistent subgroup ($11,941; each adjusted pairwise comparison, P < 0.001). Mean migraine-specific total direct costs were significantly lower for the persistent subgroup ($2,420) versus PMM2 and PMM3 subgroups and escalated with increasing numbers of drug class discontinuations or switches, from a mean of $2,997 to $5,004 (both adjusted pairwise comparisons, P < 0.001). Subgroup differences in all-cause and migraine-specific direct costs were primarily due to variations in outpatient and emergency department services., Conclusions: All-cause total direct costs rose with increasing number of PMM switches over the 12-month post-index period, and were significantly higher than in the persistent subgroup, with the exception of PMM1. Additional analyses indicated that the lack of increase between PMM-persistent and PMM1 costs was due to higher pharmacy costs that were likely related to continuous use of medication in the PMM-persistent subgroup. These data suggest an increased cost burden among patients with migraine who cycle through ≥ 2 PMMs versus those who continue to receive their initial medication class., Disclosures: Eli Lilly and Company was the sole sponsor and funder for this study and was responsible for the study design, data collection, data analysis, interpretation of data, and decision to publish the findings. All authors are employees and minor stockholders of Eli Lilly and Company. Nyhuis was employed by Eli Lilly and Company at the time of this study. The findings of this study were presented in part at the 18th Congress of the International Headache Society; September 7-10, 2017; Vancouver, Canada.

Antidepressant prescribing patterns have changed globally over the past few years, with conventional drugs including tricyclic antidepressants and monoamine oxidase inhibitors being replaced by selective serotonin reuptake inhibitors (SSRIs) and novel antidepressants. The objective of this study was to assess antidepressant utilization in Iran from 2006 to 2013 and to show Iran's situation in antidepressant consumption compared with other countries. A cross-sectional study was undertaken using prescription claims data from Iranian insurance agencies. In addition, total antidepressant sales data were obtained from the databank of the national regulatory authority. Medicines were classified according to the Anatomic Therapeutic Chemical (ATC-2012 edition) System. The Organisation for Economic Co-operation and Development data were used to compare national results from Iran with other countries. Antidepressant sales were four-fold higher than those of prescribed antidepressants [24 defined daily doses (DDD)/1000 inhabitants/day were sold whereas 6 DDD/1000 inhabitants/day were prescribed in 2013]. The trend in antidepressant prescriptions and consumption showed increasing use of SSRIs (N06AB). Nortriptyline, fluoxetine, and citalopram accounted for more than 60% of all prescriptions each year. The type of adverse reactions with new expensive antidepressants may seem convincing for the growing tendency toward using these medicines, but considering their high costs, health policymakers have to be aware of the risk of overprescription of newer antidepressant. Drivers of over-the-counter purchase of antidepressants need to be explored., Competing Interests: The authors declare no conflicts of interest., (© Atlantis Press International B.V.)

Background: Depression is usually managed in primary care and antidepressants are often the first-line treatment, but only half of those treated respond to a single antidepressant., Objectives: To investigate whether or not combining mirtazapine with serotonin-noradrenaline reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) antidepressants results in better patient outcomes and more efficient NHS care than SNRI or SSRI therapy alone in treatment-resistant depression (TRD)., Design: The MIR trial was a two-parallel-group, multicentre, pragmatic, placebo-controlled randomised trial with allocation at the level of the individual., Setting: Participants were recruited from primary care in Bristol, Exeter, Hull/York and Manchester/Keele., Participants: Eligible participants were aged ≥ 18 years; were taking a SSRI or a SNRI antidepressant for at least 6 weeks at an adequate dose; scored ≥ 14 points on the Beck Depression Inventory-II (BDI-II); were adherent to medication; and met the International Statistical Classification of Diseases and Related Health Problems , Tenth Revision, criteria for depression., Interventions: Participants were randomised using a computer-generated code to either oral mirtazapine or a matched placebo, starting at a dose of 15 mg daily for 2 weeks and increasing to 30 mg daily for up to 12 months, in addition to their usual antidepressant. Participants, their general practitioners (GPs) and the research team were blind to the allocation., Main Outcome Measures: The primary outcome was depression symptoms at 12 weeks post randomisation compared with baseline, measured as a continuous variable using the BDI-II. Secondary outcomes (at 12, 24 and 52 weeks) included response, remission of depression, change in anxiety symptoms, adverse events (AEs), quality of life, adherence to medication, health and social care use and cost-effectiveness. Outcomes were analysed on an intention-to-treat basis. A qualitative study explored patients' views and experiences of managing depression and GPs' views on prescribing a second antidepressant., Results: There were 480 patients randomised to the trial (mirtazapine and usual care, n  = 241; placebo and usual care, n  = 239), of whom 431 patients (89.8%) were followed up at 12 weeks. BDI-II scores at 12 weeks were lower in the mirtazapine group than the placebo group after adjustment for baseline BDI-II score and minimisation and stratification variables [difference -1.83 points, 95% confidence interval (CI) -3.92 to 0.27 points; p  = 0.087]. This was smaller than the minimum clinically important difference and the CI included the null. The difference became smaller at subsequent time points (24 weeks: -0.85 points, 95% CI -3.12 to 1.43 points; 12 months: 0.17 points, 95% CI -2.13 to 2.46 points). More participants in the mirtazapine group withdrew from the trial medication, citing mild AEs (46 vs. 9 participants)., Conclusions: This study did not find convincing evidence of a clinically important benefit for mirtazapine in addition to a SSRI or a SNRI antidepressant over placebo in primary care patients with TRD. There was no evidence that the addition of mirtazapine was a cost-effective use of NHS resources. GPs and patients were concerned about adding an additional antidepressant., Limitations: Voluntary unblinding for participants after the primary outcome at 12 weeks made interpretation of longer-term outcomes more difficult., Future Work: Treatment-resistant depression remains an area of important, unmet need, with limited evidence of effective treatments. Promising interventions include augmentation with atypical antipsychotics and treatment using transcranial magnetic stimulation., Trial Registration: Current Controlled Trials ISRCTN06653773; EudraCT number 2012-000090-23., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 22, No. 63. See the NIHR Journals Library website for further project information., Competing Interests: Simon Gilbody is deputy chairperson of the Health Technology Assessment programme Commissioning Board. Tim J Peters chaired the Medical Research Council–National Institute for Health Research Methodology Research Programme panel from 2007 to 2014. Ian Anderson has received personal fees from the following: Alkermes plc, Lundbeck Ltd, Otsuka Pharmaceutical Ltd, Janssen Ltd and Takeda Pharmaceutical Company Ltd.

Direct-to-consumer advertising (DTCA) for prescription drugs is a relatively unique feature of the US health care system and a source of tens of billions of dollars in annual spending. It has also garnered the attention of researchers and policymakers interested in its implications for firm and consumer behavior. However, few economic studies have explored the DTCA response to public policies, especially those mandating coverage of these products. We use detailed advertising expenditure data to assess if pharmaceutical firms increase their marketing efforts after the implementation of relevant state and federal health insurance laws. We focus on mental health parity statutes and related drug therapies-a potentially ripe setting for inducing stronger consumer demand. We find no clear indication that firms expect greater value from DTCA after these regulatory changes. DTCA appears driven by other considerations (e.g., product debut); however, it remains a possibility that firms respond to these laws through other, unobserved channels (e.g., provider detailing).

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 examine the within-trial costs and cost-effectiveness of using PARO, compared with a plush toy and usual care, for reducing agitation and medication use in people with dementia in long-term care., Design: An economic evaluation, nested within a cluster-randomized controlled trial., Setting: Twenty-eight facilities in South-East Queensland, Australia., Participants: A total of 415 residents, all aged 60 years or older, with documented diagnoses of dementia., Intervention: Facilities were randomized to 1 of 3 groups: PARO (individual, nonfacilitated 15-minute sessions, 3 afternoons per week for 10 weeks); plush toy (as per PARO but with artificial intelligence disabled); and usual care., Measurements: The incremental cost per Cohen-Mansfield Agitation Inventory-Short Form (CMAI-SF) point averted from a provider's perspective. Australian New Zealand Clinical Trials Registry (BLINDED FOR REVIEW)., Results: For the within-trial costs, the PARO group was $50.47 more expensive per resident compared with usual care, whereas the plush toy group was $37.26 more expensive than usual care. There were no statistically significant between-group differences in agitation levels after the 10-week intervention. The point estimates of the incremental cost-effectiveness ratios were $13.01 for PARO and $12.85 for plush toy per CMAI-SF point averted relative to usual care., Conclusion: The plush toy used in this study offered marginally greater value for money than PARO in improving agitation. However, these costs are much lower than values estimated for psychosocial group activities and sensory interventions, suggesting that both a plush toy and the PARO are cost-effective psychosocial treatment options for agitation., (Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Importance: Electroconvulsive therapy (ECT) is a highly effective treatment for depression but is infrequently used owing to stigma, uncertainty about indications, adverse effects, and perceived high cost., Objective: To assess the cost-effectiveness of ECT compared with pharmacotherapy/psychotherapy for treatment-resistant major depressive disorder in the United States., Design, Setting, and Participants: A decision analytic model integrating data on clinical efficacy, costs, and quality-of-life effects of ECT compared with pharmacotherapy/psychotherapy was used to simulate depression treatment during a 4-year horizon from a US health care sector perspective. Model input data were drawn from multiple meta-analyses, randomized trials, and observational studies of patients with depression. Where possible, data sources were restricted to US-based studies of nonpsychotic major depression. Data were analyzed between June 2017 and January 2018., Interventions: Six alternative strategies for incorporating ECT into depression treatment (after failure of 0-5 lines of pharmacotherapy/psychotherapy) compared with no ECT., Main Outcomes and Measures: Remission, response, and nonresponse of depression; quality-adjusted life-years; costs in 2013 US dollars; and incremental cost-effectiveness ratios. Strategies with incremental cost-effectiveness ratios of $100 000 per quality-adjusted life-year or less were designated cost-effective., Results: Based on the Sequenced Treatment Alternatives to Relieve Depression trial, we simulated a population with a mean (SD) age of 40.7 (13.2) years, and 62.2% women. Over 4 years, ECT was projected to reduce time with uncontrolled depression from 50% of life-years to 33% to 37% of life-years, with greater improvements when ECT is offered earlier. Mean health care costs were increased by $7300 to $12 000, with greater incremental costs when ECT was offered earlier. In the base case, third-line ECT was cost-effective, with an ICER of $54 000 per quality-adjusted life-year. Third-line ECT remained cost-effective in a range of univariate, scenario, and probabilistic sensitivity analyses. Incorporating all input data uncertainty, we estimate a 74% to 78% likelihood that at least 1 of the ECT strategies is cost-effective and a 56% to 58% likelihood that third-line ECT is the optimal strategy., Conclusions and Relevance: For US patients with treatment-resistant depression, ECT may be an effective and cost-effective treatment option. Although many factors influence the decision to proceed with ECT, these data suggest that, from a health-economic standpoint, ECT should be considered after failure of 2 or more lines of pharmacotherapy/psychotherapy.

Background: Physician's intention to prescribe drugs could potentially be used to improve targeting of alcohol interventions and enhanced disease management to patients with a high risk of severe alcohol-related harm within outpatient settings., Methods: Comparison of ten-year incidence trajectories of 13.8 million reimbursed purchases of prescription drugs among 303,057 Finnish men and women of whom 7490 ultimately died due to alcohol-related causes (Alc+), 14,954 died without alcohol involvement (Alc-), and 280,613 survived until the end of 2007., Results: 5-10 years before death, 88% of the persons with an Alc+ death had received prescription medication, and over two-thirds (69%) had at least one reimbursed purchase of drugs for the alimentary tract and metabolism, the cardiovascular system, or the nervous system. Among persons with an Alc+ death, the incidence rate (IR) for purchases of hypnotics, and sedatives was 1.38 times higher (95% confidence interval (CI):1.32,1.44) compared to those with an Alc- death, and 4.07 times higher (95%CI:3.92,4.22) compared to survivors; and the IR for purchases of anxiolytics was 1.40 times higher (95%CI:1.34,1.47) compared to those with an Alc- death, and 3.61 times higher (95%CI:3.48,3.78) compared to survivors., Conclusions: Using physician's intention to prescribe drugs affecting the alimentary tract and metabolism, cardiovascular system and nervous system could potentially be used to flag patients who might benefit from screening, targeted interventions or enhanced disease management. In particular, patients who are to be prescribed anxiolytics, hypnotics, and sedatives, and antidepressants may benefit from enhanced interventions targeted to problem drinking., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.

Background: In a previous single center study we found that a standardized drug treatment algorithm (ALGO) was more cost effective than treatment as usual (TAU) for inpatients with major depression. This report aimed to determine whether this promising initial finding could be replicated in a multicenter study., Methods: Treatment costs were calculated for two time periods: the study period (from enrolment to exit from study) and time in hospital (from enrolment to hospital discharge) based on daily hospital charges. Cost per remitted patient during the study period was considered as primary outcome., Results: 266 patients received ALGO and 84 received TAU. For the study period, ALGO costs were significantly lower than TAU (ALGO: 7 848 ± 6 065 €; TAU: 10 033 ± 7 696 €; p = 0.04). For time in hospital, costs were not different (ALGO: 14 734 ± 8 329 €; TAU: 14 244 ± 8 419 €; p = 0.617). Remission rates did not differ for the study period (ALGO: 57.9%, TAU: 50.0%; p=0.201). Remission rates were greater in ALGO (83.3%) than TAU (66.2%) for time in hospital (p = 0.002). Cost per remission was lower in ALGO (13 554 ± 10 476 €) than TAU (20 066 ± 15 391 €) for the study period (p < 0.001) and for time in hospital (ALGO: 17 582 ± 9 939 €; TAU: 21 516 ± 12 718 €; p = 0.036)., Limitations: Indirect costs were not assessed. Different dropout rates in TAU and ALGO complicated interpretation., Conclusions: Treatment algorithms enhance the cost effectiveness of the care of depressed inpatients, which replicates our prior results in an independent sample., (Copyright © 2017. Published by Elsevier B.V.)

Background: Although the clinical and health economic characteristics of commercially insured adults with treatment-resistant depression (TRD) have been well characterized, little is known about TRD in the Medicaid population., Objective: To describe clinical and health economic characteristics of adult Medicaid beneficiaries with TRD., Methods: Retrospective longitudinal cohort analyses were performed with Truven Health MarketScan Medicaid Database (2008-2014), focusing on adults with major depressive disorder (MDD) following an index antidepressant prescription. TRD was operationally defined as starting a third treatment regimen after 2 adequate regimens of antidepressants or augmentation therapy within 12 months of an index antidepressant prescription. Among patients with and without TRD, percentages with inpatient admissions, emergency department visits, and outpatient visits (all cause, mental health related, and depression related) were determined. Logistic regression models were used to examine associations between TRD status and use of inpatient, outpatient, and emergency services. Separate analyses were performed for the first and second year after the index antidepressant prescription., Results: Approximately one quarter (25.9%) of pharmacologically treated adults with MDD met criteria for TRD. In relation to MDD patients without TRD, patients with TRD were proportionately more likely to be older, male, and white. Compared with MDD patients without TRD, patients with TRD were also significantly more likely to receive inpatient care for any cause (31.0% vs. 21.6%; P < 0.001), a mental health-related reason (12.7% vs. 7.6%; P < 0.001), or depression (10.1% vs. 6.1%; P < 0.001) during the first year following their index antidepressant prescription. Over the second follow-up year, patients with TRD continued to be more likely than patients without TRD to receive inpatient care for any reason (26.7% vs. 19.5%; P < 0.001), a mental health-related reason (5.6% vs. 2.7%; P < 0.001), and depression (3.7% vs. 1.7%; P < 0.001). The mean health care costs of patients with TRD were also significantly higher than the costs of patients without TRD during the first year ($18,982 [SD ± $35,276] vs. $11,642 [SD ± $29,203]) and second year ($17,997 [SD ± $34,146] vs. $10,325 [SD ± $28,224]) following the index antidepressant prescription., Conclusions: In the U.S. Medicaid program, adults with TRD have substantially and persistently higher health care costs than their counterparts who do not meet criteria for TRD. The service use and health care cost patterns of patients with TRD in the Medicaid program highlight challenges of developing interventions and care coordination strategies to meet their complex clinical needs., Disclosures: This project was sponsored by Janssen Scientific Affairs. Olfson received a grant from Janssen Scientific Affairs through Columbia University Medical Center. Amos and Benson are employees of Janssen Scientific Affairs. Marcus was paid by Janssen Scientific Affairs to provide consulting support for this study and reports fees from Sunovion Pharmaceuticals and Alkermes outside of this study. McRae was a fellow affiliated with Janssen Scientific Affairs during the development of this research and manuscript. Study concept and design were contributed by Amos, Olfson, Marcus, Benson, and McRae. Data analysis was performed by all the authors. The manuscript was primarily written by Olfson, along with the other authors, and revised by McRae, Benson, Amos, Marcus, and Olfson. A different data cut from the same database was presented previously at the 2017 Annual Meeting of the International Society for Pharmacoeconomics and Outcomes Research; May 20-24, 2017; Boston, MA; and the 2017 AcademyHealth Annual Research Meeting; June 25-27, 2017; New Orleans, LA.