Safety and tolerability of long-acting injectable versus oral antipsychotics

A meta-analysis of randomized controlled studies comparing the same antipsychotics

Fuminari Misawa, Taishiro Kishimoto, Katsuhiko Hagi, John M. Kane, Christoph U. Correll

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Objective We aimed to assess whether long-acting injectable antipsychotics (LAIs), which are initiated in a loading strategy or overlapping with oral antipsychotics (OAPs) and which cannot be stopped immediately, are associated with greater safety/tolerability issues than OAPs. Method Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing LAIs and OAPs, including only LAI-OAP pairs of the same OAP (allowing oral risperidone and paliperidone as comparators for either risperidone or paliperidone LAI). Primary outcome was treatment discontinuation due to adverse events. Secondary outcomes included serious adverse events, death, ≥ 1 adverse event and individual adverse event rates. Results Across 16 RCTs (n = 4902, mean age = 36.4 years, males = 65.8%, schizophrenia = 99.1%) reporting on 119 adverse event outcomes, 55 (46.2%) adverse events were reported by ≥ 2 studies allowing a formal meta-analysis. Out of all 119 reported adverse events, LAIs and OAPs did not differ significantly regarding 115 (96.6%). LAIs were similar to OAPs regarding the frequency of treatment discontinuation due to adverse events, serious adverse events, all-cause death and death for reasons excluding accident or suicide. Compared to OAPs, LAIs were associated with significantly more akinesia, low-density lipoprotein cholesterol change and anxiety. Conversely, LAIs were associated with significantly lower prolactin change. Conclusion LAIs and OAPs did not differ on all serious and > 90% of individual adverse events. However, more studies focusing on adverse event frequencies, severity and time course associated with LAI vs OAP formulations of the same antipsychotic are needed. Additionally, adverse events data for LAIs after stopping overlapping oral antipsychotic treatment are needed.

Original languageEnglish
Pages (from-to)220-230
Number of pages11
JournalSchizophrenia Research
Volume176
Issue number2-3
DOIs
Publication statusPublished - 2016 Oct 1

Fingerprint

Antipsychotic Agents
Meta-Analysis
Safety
Injections
Risperidone
Randomized Controlled Trials
Prolactin
LDL Cholesterol
Suicide
Accidents
Cause of Death
Schizophrenia
Anxiety

Keywords

  • Adverse events
  • Long-acting injectable antipsychotics
  • Meta-analysis
  • Oral antipsychotics
  • Randomized controlled trial
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Safety and tolerability of long-acting injectable versus oral antipsychotics : A meta-analysis of randomized controlled studies comparing the same antipsychotics. / Misawa, Fuminari; Kishimoto, Taishiro; Hagi, Katsuhiko; Kane, John M.; Correll, Christoph U.

In: Schizophrenia Research, Vol. 176, No. 2-3, 01.10.2016, p. 220-230.

Research output: Contribution to journalArticle

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abstract = "Objective We aimed to assess whether long-acting injectable antipsychotics (LAIs), which are initiated in a loading strategy or overlapping with oral antipsychotics (OAPs) and which cannot be stopped immediately, are associated with greater safety/tolerability issues than OAPs. Method Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing LAIs and OAPs, including only LAI-OAP pairs of the same OAP (allowing oral risperidone and paliperidone as comparators for either risperidone or paliperidone LAI). Primary outcome was treatment discontinuation due to adverse events. Secondary outcomes included serious adverse events, death, ≥ 1 adverse event and individual adverse event rates. Results Across 16 RCTs (n = 4902, mean age = 36.4 years, males = 65.8{\%}, schizophrenia = 99.1{\%}) reporting on 119 adverse event outcomes, 55 (46.2{\%}) adverse events were reported by ≥ 2 studies allowing a formal meta-analysis. Out of all 119 reported adverse events, LAIs and OAPs did not differ significantly regarding 115 (96.6{\%}). LAIs were similar to OAPs regarding the frequency of treatment discontinuation due to adverse events, serious adverse events, all-cause death and death for reasons excluding accident or suicide. Compared to OAPs, LAIs were associated with significantly more akinesia, low-density lipoprotein cholesterol change and anxiety. Conversely, LAIs were associated with significantly lower prolactin change. Conclusion LAIs and OAPs did not differ on all serious and > 90{\%} of individual adverse events. However, more studies focusing on adverse event frequencies, severity and time course associated with LAI vs OAP formulations of the same antipsychotic are needed. Additionally, adverse events data for LAIs after stopping overlapping oral antipsychotic treatment are needed.",
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