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

Published online by Cambridge University Press:  21 November 2013

T. Kishi ,
H. Y. Meltzer ,
Y. Matsuda  and
N. Iwata
T. Kishi*
Affiliation:
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
H. Y. Meltzer
Affiliation:
Division of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Y. Matsuda
Affiliation:
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
N. Iwata
Affiliation:
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
*
*Address for correspondence: T. Kishi, M.D., Ph.D., Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. (Email: [email protected])
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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

Buspironegepironeipsapironemajor depressive disorder; meta-analysisserotonin1A receptor partial agonistzalospirone
Type
Review Article
Information
Psychological Medicine , Volume 44 , Issue 11 , August 2014 , pp. 2255 - 2269
Copyright
Copyright © Cambridge University Press 2013 

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