Among patients with schizophrenia, poor adherence and persistence with oral atypical antipsychotics (OAA) often results in relapse and hospitalization. Second-generation antipsychotic long-acting injectables (SGA LAI) have demonstrated higher adherence than first-generation antipsychotic LAI and OAA therapies. This study aimed to determine whether SGA LAIs are associated with better persistency compared to OAA among Medicaid recipients with schizophrenia. From the MarketScan Medicaid Database (January 1, 2010-June 30, 2016), patients aged ≥18 years with schizophrenia and ≥2 pharmacy claims more than 90 days apart for the same SGA LAI or OAA were selected. New users of the specific antipsychotic agent were classified, based on their index agent, as: OAA, paliperidone palmitate LAI (PPLAI), aripiprazole LAI (ALAI), and risperidone LAI (RLAI). Discontinuation during 1 year of follow-up was defined as a ≥ 60-day gap in the index OAA or SGA LAI medication past the exhaustion of the previous claim's supply. Inverse probability of treatment weights (IPTW) balanced the cohort characteristics, and weight outliers (<0.1 or >0.9) were excluded. IPTW-weighted Cox proportional hazards regression estimated hazard ratios for discontinuation. Cohorts included 7,029 OAA, 4,302 PPLAI, 586 ALAI, and 1,456 RLAI patients. Mean age was 38.0-41.0 years and 44.0-46.6% were female. Persistence was significantly longer in the SGA LAI cohorts than in the OAA cohort. Adjusted hazard ratios (95% confidence intervals) for discontinuation were 0.60 (0.56-0.64) for PPLAI, 0.69 (0.60-0.79) for ALAI, and 0.70 (0.64-0.77) for RLAI vs OAA. Results may not be generalizable to patients covered by commercial or Medicare insurance, and limitations inherent to any claims-based retrospective analysis apply. SGA LAI may be a valuable option for treating schizophrenia given the improvement in persistence.

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