COSTS ASSOCIATED WITH ADJUNCTIVE ATYPICAL ANTIPSYCHOTIC– RELATED WEIGHT GAIN AMONG PATIENTS WITH MAJOR DEPRESSIVE DISORDER: AN ECONOMIC MODEL USING NUMBERS NEEDED TO HARM

Introduction

The economic burden of major depressive disorder (MDD) is significant and includes costs due to treatment-related adverse events such as weight gain. In this economic modeling study, we quantified real-world direct costs associated with weight gain in patients initiating an atypical antipsychotic (AA) as adjunctive therapy for MDD (aMDD), then applied clinical trial–derived numbers needed to harm (NNHs) for weight gain to compare costs among AAs approved for aMDD.

Methods

Electronic medical records and claims from the Optum Market Clarity Dataset (1/1/2008–6/30/2022) were used to identify adults with a diagnosis of MDD who initiated aripiprazole, brexpiprazole, cariprazine, or quetiapine extended-release (XR) (1st dispensing=index) adjunctive to antidepressant therapy (ADT). Patients were required to have continuous health plan enrollment for ≥6 months before and after index, ≥2 months of continuous postindex AA use, and evidence of concurrent use of ADT with the index AA. Adjunctive AA–related weight gain was defined as ≥7% increase in body weight within 3 months of AA initiation relative to the latest preindex (≤3 months) measurement. Follow-up healthcare costs were evaluated from 3 to 6 months postindex and included medical (ie, hospitalizations, emergency department visits, and outpatient visits) and pharmacy costs per patient per month (PPPM). The incremental cost of adjunctive AA–related weight gain was assessed as the mean difference in costs between patients with and without weight gain, with cohorts balanced based on baseline demographic, clinical, and economic characteristics using inverse probability of treatment weighting. To estimate the comparative costs of treatmentrelated weight gain per 100 patients treated with each adjunctive AA, previously published NNHs from placebo-controlled trials were applied as measures of weight gain incidence. NNHs were reported with 95% CIs or described as “ns” if the 95% CI included infinity. The perspective was that of the US payer; all costs were converted to 2023 US dollars.

Results

In the real-world analysis, a total of 3534 eligible patients were identified, 350 of whom were considered to have adjunctive AA–related weight gain. Mean (SD) unweighted total medical and pharmacy costs were $5415 ($18,458) and $3995 ($11,812) PPPM in patients with and without weight gain, respectively. The weighted incremental cost (95% CI) associated with weight gain was $1414 ($30, $2798) PPPM (P=.045). Clinical trial–derived NNHs (95% CI) vs placebo for weight gain associated with aMDD were 131 (ns) for cariprazine, 24 (17, 45) for aripiprazole, 38 (21, 177) for quetiapine XR, and 52 (ns) for brexpiprazole. Applying these NNHs to average real-world costs yielded monthly incremental adjunctive AA–related weight gain costs per 100 patients of $1079 for cariprazine, $2719 for brexpiprazole, $3721 for quetiapine XR, and $5892 for aripiprazole.

Conclusions

Real-world patients treated with AAs for aMDD who experienced weight gain had significantly higher healthcare costs by $1414 (95% CI: $30, $2798) PPPM versus those who did not gain weight. Based on aMDD clinical trial–derived NNHs, the risk of excessive weight gain with cariprazine was lower than with aripiprazole, quetiapine XR, and brexpiprazole; therefore, the estimated cost of adjunctive AA–related weight gain was lower with cariprazine than the other AAs studied.