Benefits and harms of Risperidone and Paliperidone for treatment of patients with Schizophrenia or Bipolar disorder: A meta-analysis involving individual participant data and clinical study reports

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Abstract

Background
Schizophrenia and bipolar disorder are severe mental illnesses which are highly prevalent worldwide. Ripseridone and Paliperidone are treatments for either illnesses, but their efficacy compared to other antipsychotics and growing reports of hormonal imbalances continue to raise concerns. As existing evidence on both antipsychotics are solely based on aggregate data, we aimed to assess the benefits and harms of Risperidone and Paliperidone in the treatment of patients with schizophrenia or bipolar
disorder, using individual participant data (IPD), clinical study reports (CSRs) and
publicly available sources (journal publications and trial registries).

Methods
We searched four mainstream databases until December 2020 for randomised
placebo-controlled trials of Risperidone, Paliperidone or Paliperidone palmitate in
patients with schizophrenia or bipolar disorder. We obtained IPD and CSRs from the
Yale University Open Data Access project. The primary outcome Positive and Negative
Syndrome Scale (PANSS) score was analysed in one-stage IPD meta-analysis.
Random-effect meta-analysis of harm outcomes involved methods for coping with rare
events. PROSPERO: CRD42019140556.

Results
Of the 35 studies, IPD meta-analysis involving 22 (63%) studies showed a significant
clinical reduction in the Positive and Negative Syndrome Scale (PANSS) in patients
receiving Risperidone (-5.83, 95%CI: -10.79 to -0.87, I 2 =8.5%, n=4 studies, 1,131
participants), Paliperidone (-6.01, -8.7 to -3.32, I 2 =4.3%, n=13, 3,821) and
Paliperidone palmitate (-7.89, -12.1 to -3.69, I 2 =2.9%, n=5, 2,209). CSRs reported
nearly two times more adverse events (4434 vs. 2296 publication, relative difference
(RD) 1.93, 1.86 to 2.00) and almost 8 times more serious adverse events (650 vs. 82;
RD 7.93, 6.32 to 9.95) than the journal publications. Meta-analyses of individual harms
from CSRs revealed a significant increased risk among several outcomes including
extrapyramidal disorder, tardive dyskinaesia and increased weight. But the difference
in relative risks between data sources were not significant. Three treatment-related
gynecomastia events occurred, and the severity of these events was considered as
mild-to-moderate.

Conclusion
IPD meta-analysis conclude that Risperidone and Paliperidone antipsychotics had a
small beneficial effect on reducing PANSS score over nine weeks, which is more
conservative than estimates from reviews based on journal publications. CSRs also
contained significantly more data on harms that were unavailable in journal
publications or trial registries.
Original languageEnglish
JournalBMC Medicine
DOIs
Publication statusPublished - 25 Aug 2021

Keywords

  • Antipsychotics
  • Risperidone
  • Paliperidone
  • Schizophrenia
  • Bipolar disorder
  • Individual participant data analysis
  • Meta-analysis
  • Clinical study reports

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