Sexual function despite hyperprolactinemia: a 24-month analysis of paliperidone palmitate versus haloperidol decanoate

Objectives: Sexual dysfunction is common in schizophrenia and may contribute to poor quality of life and non-adherence. Paliperidone palmitate (PP) and haloperidol decanoate (HD) differ substantially in prolactin liability, but their long-term effects on sexual function are unclear. We compared 24-month ASEX trajectories and prolactin–ASEX associations in the ACLAIMS trial. Methods: In participants with ≥1 ASEX assessment, ASEX total score (5–30) was modelled longitudinally with mixed-effects models for repeated measures (MMRM); the binary sexual-dysfunction outcome was modelled with generalised estimating equations (GEE). Prolactin was assessed from months −0.5–24, and prolactin–ASEX associations were examined by sex. Results: 175 participants were included (PP n = 86; HD n = 89). Baseline dysfunction prevalence was 49% in both arms. PP produced higher prolactin throughout follow-up (all p<.001), but ASEX trajectories did not differ significantly. An exploratory month 22–24 window comparison favoured PP (p=.019). Greater prolactin rise from baseline was associated with overall ASEX worsening at month 12 (r = 0.21, p=.013), with concordant but non-significant sex-specific estimates (males r = 0.15; females r = 0.30). Conclusion: Despite higher prolactin with PP, ASEX trajectories were similar between PP and HD. A late PP-favouring signal was observed. Greater within-person prolactin increase was associated with later sexual-function worsening across the cohort.