Long-acting injectable antipsychotics for prevention of relapse in bipolar disorder

A systematic review and meta-analyses of randomized controlled trials

Taro Kishi, Kazuto Oya, Nakao Iwata

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

Background: This meta-analysis of randomized controlled trials aimed to examine the advantages of long-acting injectable antipsychotics over placebo or oral medications regarding efficacy and safety for patients with bipolar disorder. Methods: Two categorical meta-analyses of randomized controlled trials were performed to compare study-defined relapse rate (primary), discontinuation rates, and individual adverse events: (1) risperidone-long-acting injectable vs placebo, and (2) long-acting injectable antipsychotics vs oral medications. Results: We identified 7 randomized controlled trials (n = 1016; long-acting injectable antipsychotics [flupenthixol (1 randomized controlled trial) and risperidone (6 randomized controlled trials) = 449]; oral medications [mood stabilizers, antidepressants, antipsychotic, or any combination of these agents = 283]; and placebo = 284). Risperidone-long-acting injectable antipsychotic was superior to placebo for study-defined relapse rate (risk ratio = 0.63, P < .0001), relapse of manic symptoms (risk ratio = 0.42, P < .00001), and all-cause discontinuation (risk ratio = 0.75, P = .007). Risperidone-long-acting injectable was associated with higher incidence of prolactin-related adverse events (risk ratio = 4.82, P = .001) and weight gain (risk ratio = 3.80, P<.0001) than placebo. The pooled long-acting injectable antipsychotics did not outperform oral medications regarding primary outcome but with significant heterogeneity (I2 = 74%). Sensitivity analysis, including only studies with rapid cycling or high frequency of relapse patients, revealed that long-acting injectable antipsychotics were superior compared to oral medications (I2 = 0%, RR = 0.58, P = .0004). However, the comparators in this sensitivity analysis did not include second-generation antipsychotic monotherapy. In sensitivity analysis, including only studies with second-generation antipsychotic monotherapy as the comparator, longacting injectable antipsychotics did not outperform second-generation antipsychotic monotherapy. Risperidone-long-acting injectable was also associated with higher incidence of prolactin-related adverse events than oral medications (RR = 2.66, P = .03). Conclusions: Long-acting injectable antipsychotics appear beneficial for relapse prevention in patients with rapid cycling. Furthermore, randomized controlled trials comparing long-acting injectable antipsychotics and oral second-generation antipsychotic using larger samples of rapid cycling patients are warranted.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalInternational Journal of Neuropsychopharmacology
Volume19
Issue number9
DOIs
Publication statusPublished - 01-01-2016

Fingerprint

Secondary Prevention
Bipolar Disorder
Antipsychotic Agents
Meta-Analysis
Randomized Controlled Trials
Injections
Risperidone
Odds Ratio
Placebos
Recurrence
Prolactin
Flupenthixol
Incidence
Patient Safety
Antidepressive Agents
Weight Gain

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

@article{b1dcda47da274f00bd7f778e11214794,
title = "Long-acting injectable antipsychotics for prevention of relapse in bipolar disorder: A systematic review and meta-analyses of randomized controlled trials",
abstract = "Background: This meta-analysis of randomized controlled trials aimed to examine the advantages of long-acting injectable antipsychotics over placebo or oral medications regarding efficacy and safety for patients with bipolar disorder. Methods: Two categorical meta-analyses of randomized controlled trials were performed to compare study-defined relapse rate (primary), discontinuation rates, and individual adverse events: (1) risperidone-long-acting injectable vs placebo, and (2) long-acting injectable antipsychotics vs oral medications. Results: We identified 7 randomized controlled trials (n = 1016; long-acting injectable antipsychotics [flupenthixol (1 randomized controlled trial) and risperidone (6 randomized controlled trials) = 449]; oral medications [mood stabilizers, antidepressants, antipsychotic, or any combination of these agents = 283]; and placebo = 284). Risperidone-long-acting injectable antipsychotic was superior to placebo for study-defined relapse rate (risk ratio = 0.63, P < .0001), relapse of manic symptoms (risk ratio = 0.42, P < .00001), and all-cause discontinuation (risk ratio = 0.75, P = .007). Risperidone-long-acting injectable was associated with higher incidence of prolactin-related adverse events (risk ratio = 4.82, P = .001) and weight gain (risk ratio = 3.80, P<.0001) than placebo. The pooled long-acting injectable antipsychotics did not outperform oral medications regarding primary outcome but with significant heterogeneity (I2 = 74{\%}). Sensitivity analysis, including only studies with rapid cycling or high frequency of relapse patients, revealed that long-acting injectable antipsychotics were superior compared to oral medications (I2 = 0{\%}, RR = 0.58, P = .0004). However, the comparators in this sensitivity analysis did not include second-generation antipsychotic monotherapy. In sensitivity analysis, including only studies with second-generation antipsychotic monotherapy as the comparator, longacting injectable antipsychotics did not outperform second-generation antipsychotic monotherapy. Risperidone-long-acting injectable was also associated with higher incidence of prolactin-related adverse events than oral medications (RR = 2.66, P = .03). Conclusions: Long-acting injectable antipsychotics appear beneficial for relapse prevention in patients with rapid cycling. Furthermore, randomized controlled trials comparing long-acting injectable antipsychotics and oral second-generation antipsychotic using larger samples of rapid cycling patients are warranted.",
author = "Taro Kishi and Kazuto Oya and Nakao Iwata",
year = "2016",
month = "1",
day = "1",
doi = "10.1093/ijnp/pyw038",
language = "English",
volume = "19",
pages = "1--10",
journal = "International Journal of Neuropsychopharmacology",
issn = "1461-1457",
publisher = "Cambridge University Press",
number = "9",

}

TY - JOUR

T1 - Long-acting injectable antipsychotics for prevention of relapse in bipolar disorder

T2 - A systematic review and meta-analyses of randomized controlled trials

AU - Kishi, Taro

AU - Oya, Kazuto

AU - Iwata, Nakao

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: This meta-analysis of randomized controlled trials aimed to examine the advantages of long-acting injectable antipsychotics over placebo or oral medications regarding efficacy and safety for patients with bipolar disorder. Methods: Two categorical meta-analyses of randomized controlled trials were performed to compare study-defined relapse rate (primary), discontinuation rates, and individual adverse events: (1) risperidone-long-acting injectable vs placebo, and (2) long-acting injectable antipsychotics vs oral medications. Results: We identified 7 randomized controlled trials (n = 1016; long-acting injectable antipsychotics [flupenthixol (1 randomized controlled trial) and risperidone (6 randomized controlled trials) = 449]; oral medications [mood stabilizers, antidepressants, antipsychotic, or any combination of these agents = 283]; and placebo = 284). Risperidone-long-acting injectable antipsychotic was superior to placebo for study-defined relapse rate (risk ratio = 0.63, P < .0001), relapse of manic symptoms (risk ratio = 0.42, P < .00001), and all-cause discontinuation (risk ratio = 0.75, P = .007). Risperidone-long-acting injectable was associated with higher incidence of prolactin-related adverse events (risk ratio = 4.82, P = .001) and weight gain (risk ratio = 3.80, P<.0001) than placebo. The pooled long-acting injectable antipsychotics did not outperform oral medications regarding primary outcome but with significant heterogeneity (I2 = 74%). Sensitivity analysis, including only studies with rapid cycling or high frequency of relapse patients, revealed that long-acting injectable antipsychotics were superior compared to oral medications (I2 = 0%, RR = 0.58, P = .0004). However, the comparators in this sensitivity analysis did not include second-generation antipsychotic monotherapy. In sensitivity analysis, including only studies with second-generation antipsychotic monotherapy as the comparator, longacting injectable antipsychotics did not outperform second-generation antipsychotic monotherapy. Risperidone-long-acting injectable was also associated with higher incidence of prolactin-related adverse events than oral medications (RR = 2.66, P = .03). Conclusions: Long-acting injectable antipsychotics appear beneficial for relapse prevention in patients with rapid cycling. Furthermore, randomized controlled trials comparing long-acting injectable antipsychotics and oral second-generation antipsychotic using larger samples of rapid cycling patients are warranted.

AB - Background: This meta-analysis of randomized controlled trials aimed to examine the advantages of long-acting injectable antipsychotics over placebo or oral medications regarding efficacy and safety for patients with bipolar disorder. Methods: Two categorical meta-analyses of randomized controlled trials were performed to compare study-defined relapse rate (primary), discontinuation rates, and individual adverse events: (1) risperidone-long-acting injectable vs placebo, and (2) long-acting injectable antipsychotics vs oral medications. Results: We identified 7 randomized controlled trials (n = 1016; long-acting injectable antipsychotics [flupenthixol (1 randomized controlled trial) and risperidone (6 randomized controlled trials) = 449]; oral medications [mood stabilizers, antidepressants, antipsychotic, or any combination of these agents = 283]; and placebo = 284). Risperidone-long-acting injectable antipsychotic was superior to placebo for study-defined relapse rate (risk ratio = 0.63, P < .0001), relapse of manic symptoms (risk ratio = 0.42, P < .00001), and all-cause discontinuation (risk ratio = 0.75, P = .007). Risperidone-long-acting injectable was associated with higher incidence of prolactin-related adverse events (risk ratio = 4.82, P = .001) and weight gain (risk ratio = 3.80, P<.0001) than placebo. The pooled long-acting injectable antipsychotics did not outperform oral medications regarding primary outcome but with significant heterogeneity (I2 = 74%). Sensitivity analysis, including only studies with rapid cycling or high frequency of relapse patients, revealed that long-acting injectable antipsychotics were superior compared to oral medications (I2 = 0%, RR = 0.58, P = .0004). However, the comparators in this sensitivity analysis did not include second-generation antipsychotic monotherapy. In sensitivity analysis, including only studies with second-generation antipsychotic monotherapy as the comparator, longacting injectable antipsychotics did not outperform second-generation antipsychotic monotherapy. Risperidone-long-acting injectable was also associated with higher incidence of prolactin-related adverse events than oral medications (RR = 2.66, P = .03). Conclusions: Long-acting injectable antipsychotics appear beneficial for relapse prevention in patients with rapid cycling. Furthermore, randomized controlled trials comparing long-acting injectable antipsychotics and oral second-generation antipsychotic using larger samples of rapid cycling patients are warranted.

UR - http://www.scopus.com/inward/record.url?scp=84992187348&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992187348&partnerID=8YFLogxK

U2 - 10.1093/ijnp/pyw038

DO - 10.1093/ijnp/pyw038

M3 - Review article

VL - 19

SP - 1

EP - 10

JO - International Journal of Neuropsychopharmacology

JF - International Journal of Neuropsychopharmacology

SN - 1461-1457

IS - 9

ER -