Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials

Pharmacopsychiatry. 2020 Jan;53(1):5-13. doi: 10.1055/a-0914-3260. Epub 2019 Jun 17.

Abstract

Background: Results of previous studies on the safety and efficacy of adjunctive reboxetine for schizophrenia have been inconsistent.

Aim: The aim of this study was to examine the efficacy and tolerability of reboxetine as an adjunct medication to antipsychotic treatment in a meta-analysis of randomized controlled trials (RCTs).

Methods: Two independent investigators extracted data for a random effects meta-analysis and assessed the quality of studies using risk of bias and the Jadad scale. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio (RR)±95% confidence intervals (CIs) were calculated.

Results: Nine RCTs (n=630) with double-blind design were identified. Reboxetine outperformed placebo in improving negative (9 RCTs, n=602, SMD: -0.47 [95% CI: -0.87, -0.07], p=0.02; I2=82%), but not the overall, positive, and general psychopathology scores. The significant therapeutic effect on negative symptoms disappeared in the sensitivity analysis after removing an outlying study and in 50% (6/12) of the subgroup analyses. Reboxetine outperformed placebo in reducing weight (3 RCTs, n=186, WMD: -3.83 kg, p=0.04; I2=92%) and body mass index (WMD: -2.23 kg/m2, p=0.04; I2=95%). Reboxetine caused dry mouth but was associated with less weight gain overall and weight gain of ≥7% of the initial weight. All-cause discontinuation and other adverse events were similar between reboxetine and placebo.

Conclusion: Adjunctive reboxetine could be useful for attenuating antipsychotic-induced weight gain, but it was not effective in treating psychopathology including negative symptoms in schizophrenia.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Body Mass Index
  • Cognition
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Patient Dropouts
  • Randomized Controlled Trials as Topic
  • Reboxetine / administration & dosage
  • Reboxetine / adverse effects
  • Reboxetine / therapeutic use*
  • Schizophrenia / drug therapy*

Substances

  • Antipsychotic Agents
  • Reboxetine