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

T. Kishi, H. Y. Meltzer, Y. Matsuda, N. Iwata

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
Pages (from-to)2255-2269
Number of pages15
JournalPsychological Medicine
Volume44
Issue number11
DOIs
Publication statusPublished - 08-2014

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

All Science Journal Classification (ASJC) codes

  • Applied Psychology
  • Psychiatry and Mental health

Cite this

@article{bc42972662bd46e4a687f59e968ed318,
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.",
author = "T. Kishi and Meltzer, {H. Y.} and Y. Matsuda and N. Iwata",
year = "2014",
month = "8",
doi = "10.1017/S0033291713002857",
language = "English",
volume = "44",
pages = "2255--2269",
journal = "Psychological Medicine",
issn = "0033-2917",
publisher = "Cambridge University Press",
number = "11",

}

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

In: Psychological Medicine, Vol. 44, No. 11, 08.2014, 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, H. Y.

AU - Matsuda, Y.

AU - Iwata, N.

PY - 2014/8

Y1 - 2014/8

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.

UR - http://www.scopus.com/inward/record.url?scp=84903274461&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903274461&partnerID=8YFLogxK

U2 - 10.1017/S0033291713002857

DO - 10.1017/S0033291713002857

M3 - Review article

C2 - 24262766

AN - SCOPUS:84903274461

VL - 44

SP - 2255

EP - 2269

JO - Psychological Medicine

JF - Psychological Medicine

SN - 0033-2917

IS - 11

ER -