Comparative efficacy of oral and long-acting injectable paliperidone on social functioning in schizophrenia: A...

Schizophrenia significantly impairs personal and social functioning. Although paliperidone is a first-line antipsychotic available in oral extended-release (ER) and long-acting injectable (LAI) formulations, their comparative effects on functional outcomes remain unclear.

We conducted a systematic review and meta-analysis of studies (2007-2024) assessing paliperidone's impact on Personal and Social Performance (PSP) scale scores. Included were 20 RCTs and 38 single-arm trials. Three-level meta-analysis with robust variance estimation (RVE) was adopted to handle non-independent repeated outcome data.

Meta-analysis of RCTs showed paliperidone significantly improved PSP scores versus placebo (pooled MD = 2.51, 95% CI: 0.23 to 4.80), with within-study heterogeneity (I² = 7.72%) and a markedly high between-study heterogeneity (I² = 78.25%). Single-arm trials showed a marked mean PSP increase of 9.46 points (95%CI: 7.75-11.17). Subgroup analyses revealed both paliperidone ER (MD = 7.25, 95% CI: 5.52 to 8.99) and LAI (MD = 4.54, 95% CI: 1.75 to 7.33) were superior to placebo, but no significant difference was found between formulations or versus other oral antipsychotics. Improvements in were most prominent in patients with marked baseline difficulties (PSP 31-50, MD = 5.45, 95% CI: 2.89 to 7.91) and in participants receiving short-term follow-up of ≤12 weeks (MD = 5.45, 95% CI: 3.25 to 7.64).

Paliperidone effectively improves personal and social functioning in schizophrenia, with no functional superiority of long-acting injectables. Formulation choice should be individualized, considering baseline function, illness phase, and adherence, rather than presuming inherent differences in functional efficacy.