Paliperidone ER and LAI show no significant difference in personal and social performance scoresPaliperidone Treatment Shows Improvement in Schizophrenia Social Performance

Schizophrenia research Published September 1, 2026 Study authors: Huang Yue, Zhang Jiarong, Ling Jie, Zhao Linghui, He Ben, Zhu Guoying PubMed ↗ DOI ↗ Editorial oversight: Dr. Ji-eun Park, MD · Brain, Mind & Pain

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Key Takeaway

Note that no significant difference exists between paliperidone ER and LAI for personal and social performance scores.

This meta-analysis evaluated the efficacy of paliperidone oral extended-release (ER) and paliperidone long-acting injectable (LAI) in patients with schizophrenia. The analysis included 20 RCTs and 38 single-arm trials to assess Personal and Social Performance (PSP) scale scores.

Key findings indicate that both paliperidone ER and LAI are superior to placebo, with mean differences of 7.25 (95% CI: 5.52 to 8.99) and 4.54 (95% CI: 1.75 to 7.33) respectively. Single-arm trials showed a marked mean increase of 9.46 points (95% CI: 7.75 to 11.17). Notably, no significant difference was found between the ER and LAI formulations, nor between paliperidone and other oral antipsychotics. Improvements were more prominent in patients with marked baseline difficulties (MD = 5.45) and those with short-term follow-up (MD = 5.45).

The authors note high between-study heterogeneity (I = 78.25%) as a limitation. Clinically, the data suggests that formulation choice should be individualized based on patient factors like baseline function and adherence, as no inherent functional superiority was established between ER and LAI formulations.

How this fits prior evidence

This meta-analysis addresses a gap in understanding the functional efficacy of different paliperidone delivery methods. While prior evidence indicates that 5-HTR antagonists improve negative symptoms and cognition in schizophrenia, this study specifically compares the functional outcomes of ER versus LAI formulations. It confirms that both formulations are effective compared to placebo, but does not establish a clinical superiority of one over the other.

A large review of 20 randomized trials and 38 single-arm trials looked at how paliperidone affects people with schizophrenia. The study specifically measured personal and social performance, which tracks how well a person functions in daily life. The researchers looked at two versions of the medicine: an extended-release oral pill and a long-acting injectable version.

Both the oral and injectable versions of paliperidone were found to be more effective than a placebo. The study also found that both versions performed similarly to other oral antipsychotic medications. Notably, there was no significant difference in effectiveness between the oral and injectable versions of paliperidone.

Patients who started with more significant difficulties showed more noticeable improvements. However, the study noted high variation between the different trials included in the analysis. Because of this variation, the results should be viewed as a general overview. Doctors can use this information to help decide which version of the medication is best for a patient based on their specific needs and daily routine.

What this means for you:

Both oral and injectable paliperidone show similar improvements in social performance for people with schizophrenia.

Common questions

Is the injectable version of paliperidone more effective than the oral version?

The study found no significant difference in effectiveness between the oral extended-release version and the long-acting injectable version of paliperidone. Both versions showed significant improvements in personal and social performance scores compared to a placebo.

Who benefits most from this treatment?

The study found that improvements in personal and social performance were more prominent in patients who had marked baseline difficulties. Additionally, more prominent improvements were noted in participants with short-term follow-up periods of 12 weeks or less.

How does paliperidone compare to other antipsychotics?

The study found no significant difference in performance scores when comparing paliperidone to other oral antipsychotic medications. Both the oral and injectable forms of paliperidone were shown to be superior to a placebo.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedSep 2026

PMID42296848

View Original Abstract ↓

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (I = 7.72%) and a markedly high between-study heterogeneity (I = 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). CONCLUSION: 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.

Paliperidone ER and LAI show no significant difference in personal and social performance scoresPaliperidone Treatment Shows Improvement in Schizophrenia Social Performance

How this fits prior evidence

Common questions

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Paliperidone ER and LAI show no significant difference in personal and social performance scoresPaliperidone Treatment Shows Improvement in Schizophrenia Social Performance

How this fits prior evidence

Common questions

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