Antipsychotic exposure shows time-dependent associations with vocational recovery in schizophrenia cohortDo antipsychotics help people with schizophrenia get back to work or school?

Background. Antipsychotic medications are recommended for schizophrenia spectrum disorders, yet their long-term effects on functional recovery remain unclear, with conflicting evidence often derived from between-subject comparisons vulnerable to confounding by indication. Methods. We conducted a nationwide register-based cohort study of 65,630 individuals with incident schizophrenia spectrum disorders in Denmark (1998-2023). We modelled antipsychotic exposure against "productive engagement" (employment or education). We used two analytical approaches: (1) within-subject stratified Cox models with time-varying covariates to eliminate time-invariant confounding; and (2) Fine-Gray competing risks models with baseline exposure, accounting for mortality and emigration. Results. Over 26.9 million person-weeks, the overall productive engagement rate was 48.2%. Integration of hospital pharmacy data revealed 6.1% exposure misclassification in studies relying solely on community records. The primary within-subject analysis revealed significant temporal heterogeneity: medication use was associated with reduced engagement rates in the acute (0-2 years: HR 0.908) and consolidation phases (2-5 years: HR 0.946), but reversed to a small positive association in the maintenance phase (5+ years: HR 1.019). The between-subject Fine-Gray model, which estimates cumulative engagement probabilities, yielded an SHR of 1.002 (95% CI 0.988-1.015), a population-level average that obscured these phase-specific dynamics. Conclusions. Antipsychotic pharmacotherapy exerts a time-dependent, biphasic impact on vocational recovery. We identified a window of vulnerability during the post-acute "consolidation" phase (years 2-5) where treatment is associated with a transient reduction in productive engagement, before becoming protective after five years. These findings challenge the assumption that symptomatic stability automatically facilitates functional reintegration.