Associations of long‐acting injectable antipsychotics and non‐clozapine antipsychotic polytherapy at discharge with treatment failure in psychotic disorders: A prospective multicenter cohort study

AIM: To evaluate the association of long-acting injectable antipsychotic (LAI) treatment with treatment failure and the association of antipsychotic polytherapy excluding clozapine (APEC) during the first 365 days and thereafter. Because APEC is generally selected after inadequate response to monotherapy, we hypothesized a less favorable association after 365 days. METHODS: This prospective multicenter cohort enrolled patients admitted to three Japanese psychiatric emergency hospitals from April 2022 through March 2023; follow-up continued through 31 March 2026. Treatment failure comprised psychiatric rehospitalization, loss to outpatient follow-up, or death after discharge. Hospital-stratified multivariable Cox models estimated the LAI association. Prespecified interval-specific analyses estimated APEC associations during the first 365 days after discharge and thereafter. RESULTS: Among 444 patients (54.5% women; mean [SD] age, 50.2 [17.1] years), 263 (59.2%) experienced treatment failure. An LAI at discharge was associated with a lower hazard of treatment failure (adjusted hazard ratio [HR], 0.67; 95% CI, 0.45-0.98; P = 0.039). HR was similar whether LAI was used as monotherapy or in combination therapy. As to APEC, the ratio of the late-period to early-period hazard ratios was 1.28 (95% CI, 0.72-2.29; P = 0.40). CONCLUSIONS: LAI use at discharge was associated with a lower hazard of treatment failure, although the association was attenuated and no longer statistically significant after adjustment for previous LAI use. Category-specific comparisons were inconclusive. There was no statistically significant evidence that the association between APEC at discharge and treatment failure differed between the first 365 days and the subsequent period. CLINICAL TRIALS REGISTRATION: UMIN-CTR (https://www.umin.ac.jp/ctr/index-j.htm), UMIN000045925.