Long-term efficacy and safety of paliperidone palmitate monthly injection and oral paliperidone extended-release tablets in schizophrenia, a randomized controlled trial

This study aimed to compare the 9-month efficacy and safety of paliperidone palmitate 1-monthly injection (PP1M) versus oral paliperidone extended-release (ER) tablets in patients with stable schizophrenia (SCZ). A single-center randomized controlled trial was conducted, enrolling 119 adult outpatients (mean age 46.03 years) diagnosed with SCZ (DSM-5 criteria), randomized to PP1M (n = 60) or ER (n = 59). The primary outcome was change in Positive and Negative Syndrome Scale (PANSS) total score, with secondary outcomes including Clinical Global Impression-Severity (CGIS) and Treatment Emergent Symptom Scale (TESS) scores. No statistically significant differences in PANSS total score improvements were observed between groups at 3, 6, and 9 months (P > 0.05). PP1M demonstrated transient superiority in CGI-S reduction at 3 and 6 months (mean difference: -0.31 and - 0.45, respectively; P < 0.05), but this difference dissipated by month 9. No significant differences in tolerability, as measured by TESS scores, were found between groups, with no significant differences in adverse events across follow-up periods. PP1M showed numerically greater (though nonsignificant) improvements in negative symptoms, suggesting potential subtle benefits. In conclusion, this study did not detect significant differences in long-term efficacy or safety between PP1M and ER in stable SCZ patients. While PP1M provided early CGI-S advantages likely attributable to adherence optimization, no inherent pharmacodynamic superiority was observed. These findings support PP1M as a pragmatic option for adherence-challenged patients, emphasizing individualized treatment selection based on preferences and feasibility.