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Background The long-term effectiveness of antipsychotic maintenance treatment after first-episode psychosis (FEP) is contested. In this real-world observational study, we examined how cumulative exposure to antipsychotics within the first 5 years from FEP was associated with the 19-year outcome. Methods Finnish national registers were used to detect all patients who were hospitalized due to non-affective psychosis in the mid-1990s, and who were treatment naïve prior to the inclusion period (N = 1318). Generalized linear models with logit link function were used to estimate how cumulative exposure to antipsychotics within the first 5 years from onset was associated with mortality, work capability, and the use of psychiatric services at the end of the 19-year follow-up. To adjust for confounding by indication, the primary outcome analyses implemented stabilized inverse probability of treatment weighting using propensity scores. Results Persons with a higher cumulative exposure to antipsychotics within the first 5 years from FEP were more likely to still be receiving antipsychotics (adjusted odds ratio [OR] = 2.1; 95% CI: 1.5−2.8), psychiatric treatment (OR = 1.4; 95% CI: 1.1−1.7), and disability allowances (OR = 1.3; 95% CI: 1.01−1.6) at the end of the 19-year follow-up, as compared to low/zero-exposure. Higher cumulative exposure was also associated with higher mortality (OR = 1.5; 95% CI: 1.1–2.1). Conclusions After adjustment for confounders, moderate and high cumulative exposure to antipsychotics within the first 5 years from FEP was consistently associated with a higher risk of adverse outcomes during the 19-year follow-up, as compared to low or zero exposure. Due to potential unmeasured confounding, controlled trials are needed.

Five-Year Cumulative Exposure to Antipsychotic Medication After First-Episode Psychosis and its Association With 19-Year Outcomes