Azapirone 5-HT1A receptor partial agonist treatment for major depressive disorder: Systematic review and meta-analysis

T. Kishi*, Herbert Y Meltzer, Y. Matsuda, N. Iwata

*Corresponding author for this work

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

Background. A meta-analysis of the serotonin1A (5-HT1A) receptor partial agonist of the azapirone class as an anxiolytic drug for the treatment of major depressive disorder (MDD) has not previously been reported. Method. We carried out a systematic review of the literature available in PubMed, the Cochrane Library database and PsycINFO up to 12 October 2013, and conducted a meta-analysis of randomized controlled trials (RCTs) comparing 5-HT1A agonists with placebo and RCTs of 5-HT1A agonist augmentation therapies for MDD treatment. We calculated the risk ratio (RR), number needed to treat (NNT)/number needed to harm (NNH) and 95% confidence intervals (CIs). Results. Fifteen RCTs comparing 5-HT1A agonists with placebo (total n=2469, four studies with buspirone, seven with gepirone, three with ipsapirone and one with zalospirone) were identified. Pooled 5-HT1A agonists had significantly more responders (RR 0.74, 95% CI 0.65-083, p<0.00001, NNT=6, 12 trials, n=1816) than placebo. Pooled 5-HT1A agonists were superior to placebo in discontinuation due to inefficacy (RR 0.49, p=0.02, NNH=16, p=0.03, 10 trials, n=1494) but were inferior to placebo in discontinuation due to side-effects (RR 1.88, p<0.0001, NNH=17, p=0.001, 13 trials, n=2196). However, all-cause discontinuation was similar in both groups (RR 0.99, p=0.85, 14 trials, n=2402). Four 5-HT1A agonist augmentation studies were identified (total n=365, three buspirone studies and one tandospirone study). There were no statistically significant effects of 5-HT1A agonist augmentation therapies on response rate (RR 0.98, p=0.85, four trials, n=341). 5-HT1A agonist-related side-effects including gastrointestinal symptoms, dizziness, insomnia, palpitation, paresthesia and sweating were greater than with placebo (p<0.00001 to p=0.03). Conclusions. Our results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.

Original languageEnglish (US)
Pages (from-to)2255-2269
Number of pages15
JournalPsychological Medicine
Volume44
Issue number11
DOIs
StatePublished - Jan 1 2014

Fingerprint

Serotonin 5-HT1 Receptor Agonists
Receptor, Serotonin, 5-HT1A
Major Depressive Disorder
Meta-Analysis
Placebos
Odds Ratio
Buspirone
Numbers Needed To Treat
Therapeutics
Randomized Controlled Trials
Confidence Intervals
Sweating
Paresthesia
Anti-Anxiety Agents
Sleep Initiation and Maintenance Disorders
Dizziness
PubMed
Libraries
Databases

Keywords

  • Buspirone
  • Gepirone
  • Ipsapirone
  • Major depressive disorder; meta-analysis
  • Zalospirone

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Applied Psychology
  • Medicine(all)

Cite this

@article{70620229fdbc4d9aa078385baecb9539,
title = "Azapirone 5-HT1A receptor partial agonist treatment for major depressive disorder: Systematic review and meta-analysis",
abstract = "Background. A meta-analysis of the serotonin1A (5-HT1A) receptor partial agonist of the azapirone class as an anxiolytic drug for the treatment of major depressive disorder (MDD) has not previously been reported. Method. We carried out a systematic review of the literature available in PubMed, the Cochrane Library database and PsycINFO up to 12 October 2013, and conducted a meta-analysis of randomized controlled trials (RCTs) comparing 5-HT1A agonists with placebo and RCTs of 5-HT1A agonist augmentation therapies for MDD treatment. We calculated the risk ratio (RR), number needed to treat (NNT)/number needed to harm (NNH) and 95{\%} confidence intervals (CIs). Results. Fifteen RCTs comparing 5-HT1A agonists with placebo (total n=2469, four studies with buspirone, seven with gepirone, three with ipsapirone and one with zalospirone) were identified. Pooled 5-HT1A agonists had significantly more responders (RR 0.74, 95{\%} CI 0.65-083, p<0.00001, NNT=6, 12 trials, n=1816) than placebo. Pooled 5-HT1A agonists were superior to placebo in discontinuation due to inefficacy (RR 0.49, p=0.02, NNH=16, p=0.03, 10 trials, n=1494) but were inferior to placebo in discontinuation due to side-effects (RR 1.88, p<0.0001, NNH=17, p=0.001, 13 trials, n=2196). However, all-cause discontinuation was similar in both groups (RR 0.99, p=0.85, 14 trials, n=2402). Four 5-HT1A agonist augmentation studies were identified (total n=365, three buspirone studies and one tandospirone study). There were no statistically significant effects of 5-HT1A agonist augmentation therapies on response rate (RR 0.98, p=0.85, four trials, n=341). 5-HT1A agonist-related side-effects including gastrointestinal symptoms, dizziness, insomnia, palpitation, paresthesia and sweating were greater than with placebo (p<0.00001 to p=0.03). Conclusions. Our results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.",
keywords = "Buspirone, Gepirone, Ipsapirone, Major depressive disorder; meta-analysis, Zalospirone",
author = "T. Kishi and Meltzer, {Herbert Y} and Y. Matsuda and N. Iwata",
year = "2014",
month = "1",
day = "1",
doi = "10.1017/S0033291713002857",
language = "English (US)",
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pages = "2255--2269",
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issn = "0033-2917",
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}

Azapirone 5-HT1A receptor partial agonist treatment for major depressive disorder : Systematic review and meta-analysis. / Kishi, T.; Meltzer, Herbert Y; Matsuda, Y.; Iwata, N.

In: Psychological Medicine, Vol. 44, No. 11, 01.01.2014, p. 2255-2269.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Azapirone 5-HT1A receptor partial agonist treatment for major depressive disorder

T2 - Systematic review and meta-analysis

AU - Kishi, T.

AU - Meltzer, Herbert Y

AU - Matsuda, Y.

AU - Iwata, N.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background. A meta-analysis of the serotonin1A (5-HT1A) receptor partial agonist of the azapirone class as an anxiolytic drug for the treatment of major depressive disorder (MDD) has not previously been reported. Method. We carried out a systematic review of the literature available in PubMed, the Cochrane Library database and PsycINFO up to 12 October 2013, and conducted a meta-analysis of randomized controlled trials (RCTs) comparing 5-HT1A agonists with placebo and RCTs of 5-HT1A agonist augmentation therapies for MDD treatment. We calculated the risk ratio (RR), number needed to treat (NNT)/number needed to harm (NNH) and 95% confidence intervals (CIs). Results. Fifteen RCTs comparing 5-HT1A agonists with placebo (total n=2469, four studies with buspirone, seven with gepirone, three with ipsapirone and one with zalospirone) were identified. Pooled 5-HT1A agonists had significantly more responders (RR 0.74, 95% CI 0.65-083, p<0.00001, NNT=6, 12 trials, n=1816) than placebo. Pooled 5-HT1A agonists were superior to placebo in discontinuation due to inefficacy (RR 0.49, p=0.02, NNH=16, p=0.03, 10 trials, n=1494) but were inferior to placebo in discontinuation due to side-effects (RR 1.88, p<0.0001, NNH=17, p=0.001, 13 trials, n=2196). However, all-cause discontinuation was similar in both groups (RR 0.99, p=0.85, 14 trials, n=2402). Four 5-HT1A agonist augmentation studies were identified (total n=365, three buspirone studies and one tandospirone study). There were no statistically significant effects of 5-HT1A agonist augmentation therapies on response rate (RR 0.98, p=0.85, four trials, n=341). 5-HT1A agonist-related side-effects including gastrointestinal symptoms, dizziness, insomnia, palpitation, paresthesia and sweating were greater than with placebo (p<0.00001 to p=0.03). Conclusions. Our results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.

AB - Background. A meta-analysis of the serotonin1A (5-HT1A) receptor partial agonist of the azapirone class as an anxiolytic drug for the treatment of major depressive disorder (MDD) has not previously been reported. Method. We carried out a systematic review of the literature available in PubMed, the Cochrane Library database and PsycINFO up to 12 October 2013, and conducted a meta-analysis of randomized controlled trials (RCTs) comparing 5-HT1A agonists with placebo and RCTs of 5-HT1A agonist augmentation therapies for MDD treatment. We calculated the risk ratio (RR), number needed to treat (NNT)/number needed to harm (NNH) and 95% confidence intervals (CIs). Results. Fifteen RCTs comparing 5-HT1A agonists with placebo (total n=2469, four studies with buspirone, seven with gepirone, three with ipsapirone and one with zalospirone) were identified. Pooled 5-HT1A agonists had significantly more responders (RR 0.74, 95% CI 0.65-083, p<0.00001, NNT=6, 12 trials, n=1816) than placebo. Pooled 5-HT1A agonists were superior to placebo in discontinuation due to inefficacy (RR 0.49, p=0.02, NNH=16, p=0.03, 10 trials, n=1494) but were inferior to placebo in discontinuation due to side-effects (RR 1.88, p<0.0001, NNH=17, p=0.001, 13 trials, n=2196). However, all-cause discontinuation was similar in both groups (RR 0.99, p=0.85, 14 trials, n=2402). Four 5-HT1A agonist augmentation studies were identified (total n=365, three buspirone studies and one tandospirone study). There were no statistically significant effects of 5-HT1A agonist augmentation therapies on response rate (RR 0.98, p=0.85, four trials, n=341). 5-HT1A agonist-related side-effects including gastrointestinal symptoms, dizziness, insomnia, palpitation, paresthesia and sweating were greater than with placebo (p<0.00001 to p=0.03). Conclusions. Our results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.

KW - Buspirone

KW - Gepirone

KW - Ipsapirone

KW - Major depressive disorder; meta-analysis

KW - Zalospirone

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U2 - 10.1017/S0033291713002857

DO - 10.1017/S0033291713002857

M3 - Review article

C2 - 24262766

AN - SCOPUS:84903274461

VL - 44

SP - 2255

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JO - Psychological Medicine

JF - Psychological Medicine

SN - 0033-2917

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