Clinical Therapeutics/Volume 41, Number 2, 2019 Medication Adherence, Health Care Utilization, and Costs in Patients With Major Depressive Disorder Initiating Adjunctive Atypical * Antipsychotic Treatment Michael S. Broder, MD, MSHS1; Mallik Greene, BPharm, PhD, DBA2; Tingjian Yan, PhD1; Eunice Chang, PhD1; Ann Hartry, PhD3; and Irina Yermilov, MD, MPH, MS1 1Partnership for Health Analytic Research, LLC, Beverly Hills, CA, USA; 2Otsuka Phar- maceutical Development & Commercialization, Inc, Princeton, NJ, USA; and 3Lundbeck, Deerfield, IL, USA ABSTRACT (HR ¼ 1.14; 95% CI, 1.00e1.29; P ¼ 0.054). The adjusted rate of all-cause hospitalization or emergency Purpose: The purpose of this study was to compare department visit in the postindex period was lowest for medication adherence, health care utilization, and cost brexpiprazole at 27.4% (95% CI, 24.0%e31.0%), among patients receiving adjunctive treatment for compared with 31.1% (95% CI, 27.3%e35.2%) for major depressive disorder (MDD) with brexpiprazole, lurasidone and 35.3% (95% CI, 33.5%e37.1%) for quetiapine, or lurasidone. quetiapine (P< 0.001 for all comparisons). Quetiapine Methods: UsingTruvenHealthMarketScan® users had increased all-cause costs compared with Commercial, Medicaid, and Medicare Supplemental brexpiprazole users (estimate ¼ $2309; 95% CI, Databases, we identified adults with MDD initiating $31e$4587; P ¼ 0.047); all-cause medical costs did not adjunctive treatment with brexpiprazole, quetiapine, or differ between lurasidone and brexpiprazole lurasidone (index atypical antipsychotic [AAP]). We (estimate ¼ $913; 95% CI, $−2033 e$3859; P ¼ 0.543). compared medication adherence and persistence Adjusted psychiatric hospital care, psychiatric costs, and measured by proportion of days covered (PDC) and PDC did not differ significantly among the groups. treatment duration of index AAP, all-cause and Implications: In patients with MDD and a variety psychiatric hospital care (hospitalization or emergency of insurance types, brexpiprazole use was associated department visit), and medical costs during 6-month with statistically significantly lower risks of follow-up. Models performed included logistic discontinuation, risk of hospital care (hospitalization regression for hospital care, linear regression for PDC and ED visits), and all-cause medical costs compared and cost, and Cox proportional hazards regression for with adjunctive quetiapine. Differences between time to discontinuation, adjusting for demographic, brexpiprazole and lurasidone were not statistically clinical, and utilization differences during the 6 months significant. These findings suggest that drug choice is before index AAP. associated with subsequent health care utilization and Findings: The total sample included 778 brexpiprazole, costs. (Clin Ther. 2019;41:221e232) 2019 The 626 lurasidone, and 3458 quetiapine therapy initiators. © Authors. Published by Elsevier Inc. This is an open Adjusting for baseline differences, the risk of access article under the CC BY-NC-ND license (http:// discontinuation of index AAP was statistically significantly creativecommons.org/licenses/by-nc-nd/4.0/). higher for quetiapine than for brexpiprazole (hazard ratio [HR] ¼ 1.13; 95% CI, 1.02e1.25; P ¼ 0.023) and did Accepted for publication December 6, 2018 not differ between lurasidone and brexipiprazole https://doi.org/10.1016/j.clinthera.2018.12.005 0149-2918/$ - see front matter * fi © 2019 The Authors. Published by Elsevier Inc. This is an open access This study was presented at ISPOR Asia Paci c 2018, article under the CC BY-NC-ND license September 8e11, 2018, Tokyo, Japan. (http://creativecommons.org/licenses/by-nc-nd/4.0/). February 2019 221 Clinical Therapeutics Key words: atypical antipsychotic, health care uti- Although lurasidone is not indicated for MDD, it was lization, major depressive disorder, costs, medication selected because it was the newest AAP, with strong adherence, secondary data analysis. evidence from a randomized clinical trial supporting use in patients with MDD.12 On the basis of our PubMed search, there are no head-to-head retrospective studies comparing these commonly used AAPs in MDD in the INTRODUCTION real-world setting. In the absence of comparative trials, Major depressive disorder (MDD), or unipolar major retrospective studies can support clinical decision depression, is characterized by a history of 1 major making. Although such evidence is always subject to depressive episodes without evidence of mania or more biases than randomized trials, retrospective hypomania. In 2015, an estimated 16.1 million studies may be larger, be more generalizable, and people in the United States had at least 1 major produce results sooner. Within the large population of depressive episode in the past year (approximately 1 patients with inadequately treated MDD, randomized in 15 of all US adults).1 MDD is associated with trials of necessity focus on a small subset of patients. To alarmingly high costs (as much as $200 billion per supplement the clinical data on the optimal year in direct and indirect costs according to 1 recent augmentation strategy for inadequately treated MDD, study2) and may be responsible for more human pain we conducted a retrospective, exploratory study using than any other mental or behavioral disorder.1 the most recent data from Medicare, Medicaid, and Furthermore, despite available therapies, costs appear commercial insurance to compare health care utilization to have increased steadily in recent decades.3 and costs among patients with MDD receiving the latest The recommended initial therapy guidelines for approved brexpiprazole with commonly used branded MDD from both the American Psychiatric Association AAPs including quetiapine or lurasidone. (APA) and the Texas Medication Algorithm Project consist of a combination of treatment with pharmacologic therapy and psychotherapy, based on METHODS trials that found the combination was more effective This was a retrospective cohort study using the e than either treatment alone.4 6 A wide variety of Truven Health Analytics MarketScan® Commercial, antidepressants can be used as initial Medicaid, and Medicare Supplemental Databases. All pharmacotherapy. Selective serotonin reuptake databases comply with the Health Insurance inhibitors are the most widely prescribed class, with Portability and Accountability Act. no clear advantage to any other particular therapy at The MarketScan Commercial Database includes preventing relapse or recurrence.7,8 Patients with medical and pharmacy claims for approximately 65 inadequate relief of symptoms after initial treatment million individuals and their dependents, who are often fare much worse over the long run.9 covered through employer-sponsored private health Two common strategies for managing depression that insurance plans. The MarketScan Medicare has not resolved with initial treatment are switching Supplemental Database contains records on treatment and augmenting initial antidepressant with an approximately 5.3 million retired employees and agent from another pharmacologic class.5,10 spouses >65 years old who are enrolled in Medicare Augmentation strategies frequently involve the use of with supplemental Medigap insurance paid by their atypical antipsychotic (AAP) medication, but there is former employers. The MarketScan Medicaid little clinical trial evidence to help clinicians choose a Database contains the pooled health care experience particular augmentation strategy.11 Both branded and of approximately 40 million Medicaid enrollees from generic options for treatment exist, and selection on the multiple states. It includes inpatient and outpatient basis of price is common. Brexpiprazole, quetiapine, services, outpatient prescription drug claims, as well and lurasidone are branded AAPs commonly used in as information on enrollment, long-term care, and this setting. Among these 3 AAPs, brexpiprazole is the other medical care. In addition to standard latest AAP approved by the US Food and Drug demographic variables, such as age and sex, the Administration (FDA) as an augmentation treatment to database includes variables of particular value to an antidepressant medication to treat adults with MDD. researchers investigating Medicaid populations (such 222 Volume 41 Number 2 M.S. Broder et al. as ethnicity, maintenance assistance status, and pharmacy claim in both the 90 days before and the 90 Medicare eligibility). days after the index date. In addition, we required at Patients with MDD were identified by the presence least 15 days’ antidepressant supply overlapping with of at least 1 inpatient or 2 outpatient claims for the first prescription of the index therapy. Patients MDD (International Classification of Diseases, Ninth who used multiple AAPs on the index date were Revision, Clinical Modification [ICD-9-CM] codes excluded. All patients were required to have 296.2x, 296.3x; International Classification of continuous enrollment for the 6 months before and Diseases, Tenth Revision, Clinical Modification [ICD- after the index date. 10-CM] codes F32.0-F32.5, F32.9, F33.0x-F33.4x, For the resulting cohorts, we compared baseline F33.9x) in any diagnosis field of a claim during the demographic characteristics, insurance type, measures study period, which was January 1, 2015 to of chronic and acute illness, and utilization and cost. December 31, 2016, for Medicaid data and January In the follow-up period, we compared medication 1, 2015 to September 30, 2016, for Commercial and persistence and adherence