Skip to main content
×
Home
    • Aa
    • Aa
  • The International Journal of Neuropsychopharmacology, Volume 16, Issue 6
  • July 2013, pp. 1259-1266

Augmentation of antipsychotic drug action by azapirone 5-HT1A receptor partial agonists: a meta-analysis

  • Taro Kishi (a1), Herbert Y. Meltzer (a2) and Nakao Iwata (a1)
  • DOI: http://dx.doi.org/10.1017/S1461145713000151
  • Published online: 03 April 2013
Abstract
Abstract

The aim of the study was to evaluate the evidence that serotonin1A (5-HT1A) receptor partial agonists of the azapirone class, which are not antipsychotic, have benefits for adjunctive treatment of overall psychopathology, positive and negative symptoms for patients with schizophrenia. We carried out a systematic review of the literature available through PubMed, Cochrane Library, PsycINFO and Google Scholar during September 2012, followed by a meta-analysis of randomized placebo-controlled trials. Risk ratio (RR), 95% confidence intervals (CI) and standardized mean difference (s.m.d.) were calculated. Four studies, involving 163 patients with schizophrenia, met inclusion criteria: buspirone: three trials and 137 patients; tandospirone: one trial and 26 patients. As adjunctive therapy, 5-HT1A partial agonists were significantly superior to placebo for overall improvement in psychopathology (s.m.d. = −0.46, CI = −0.79 to −0.13, p = 0.006, N = 4, n = 149) and marginally more effective to improve positive symptoms (s.m.d. = −0.31, CI = −0.64 to 0.01, p = 0.06, N = 4, n = 149). However, 5-HT1A partial agonists were not more efficacious than placebo as adjunctive therapy for improving negative symptoms (s.m.d. = −0.09, CI = −0.60 to 0.42, p = 0.72, N = 4, n = 149). In addition, there was no significant difference in discontinuation rates between 5-HT1A partial agonists and placebo (all cause: RR = 0.98, CI = 0.49–1.98, p = 0.96, N = 4, n = 153, side-effects: RR = 1.96, CI = 0.54–7.19, p = 0.31, N = 4, n = 153). 5-HT1A partial agonists as adjunctive therapy improved overall psychopathology with a trend to improve positive symptoms in patients with schizophrenia. Because the number of studies was small, additional controlled clinical trials with larger numbers of patients are indicated.

Copyright
Corresponding author
Address for correspondence: Dr T. Kishi, Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. Tel:+81 562 93 9250Fax:+81 562 93 1831Email:tarok@fujita-hu.ac.jp
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

NC Andreasen (1982) Negative symptoms in schizophrenia. Definition and reliability. Arch Gen Psychiatry 39:784788.

L Bardin , A Auclair , MS Kleven , EP Prinssen , W Koek , A Newman-Tancredi , R Depoortere (2007) Pharmacological profiles in rats of novel antipsychotics with combined dopamine D2/serotonin 5-HT1A activity: comparison with typical and atypical conventional antipsychotics. Behav Pharmacol 18:103118.

MW Beltman , RC Voshaar , AE Speckens (2010) Cognitive-behavioural therapy for depression in people with a somatic disease: meta-analysis of randomised controlled trials. Br J Psychiatry 197:1119.

AF Carvalho , JR Machado , JL Cavalcante (2009) Augmentation strategies for treatment-resistant depression. Curr Opin Psychiatry 22:712.

LD Cohn , BJ Becker (2003) How meta-analysis increases statistical power. Psychol Methods 8:243253.

R DerSimonian , N Laird (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177188.

A Ghaleiha , AA Noorbala , F Farnaghi , M Hajiazim , S Akhondzadeh (2010) A double-blind, randomized, and placebo-controlled trial of buspirone added to risperidone in patients with chronic schizophrenia. J Clin Psychopharmacol 30:678682.

JG Hensler (2003) Regulation of 5-HT1A receptor function in brain following agonist or antidepressant administration. Life Sci 72:16651682.

JP Higgins , SG Thompson , JJ Deeks , DG Altman (2003) Measuring inconsistency in meta-analyses. BMJ 327:557560.

M Horiguchi , HY Meltzer (2012) The role of 5-HT1A receptors in phencyclidine (PCP)-induced novel object recognition (NOR) deficit in rats. Psychopharmacology 221:205215.

M Horiguchi , KE Hannaway , AE Adelekun , K Jayathilake , HY Meltzer (2012) Prevention of the phencyclidine-induced impairment in novel object recognition in female rats by co-administration of lurasidone or tandospirone, a 5-HT(1A) partial agonist. Neuropsychopharmacology 37:21752183.

HC Jackson , DJ Nutt (1992) Effects of benzodiazepine receptor inverse agonists on locomotor activity and exploration in mice. Eur J Pharmacol 221:199203.

B Le Francois , M Czesak , D Steubl , PR Albert (2008) Transcriptional regulation at a HTR1A polymorphism associated with mental illness. Neuropharmacology 55:977985.

GK Matheson , DM Pfeifer , MB Weiberg , C Michel (1994) The effects of azapirones on serotonin1A neurons of the dorsal raphe. Gen Pharmacol 25:675683.

HY Meltzer , M Huang (2008) In vivo actions of atypical antipsychotic drug on serotonergic and dopaminergic systems. Prog Brain Res 172:177197.

HY Meltzer , BW Massey (2011) The role of serotonin receptors in the action of atypical antipsychotic drugs. Curr Opin Pharmacol 11:5967.

HY Meltzer , T Sumiyoshi (2008) Does stimulation of 5-HT(1A) receptors improve cognition in schizophrenia? Behav Brain Res 195:98102.

HY Meltzer , Z Li , Y Kaneda , J Ichikawa (2003) Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 27:11591172.

S Miyamoto , GE Duncan , CE Marx , JA Lieberman (2005) Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry 10:79104.

NC Moore , E Meyendorff , V Yeragani , PA LeWitt , S Gershon (1987) Tiaspirone in schizophrenia. J Clin psychopharmacol 7:98101.

A Newman-Tancredi , MS Kleven (2011) Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties. Psychopharmacology 216:451473.

SV Onrust , K McClellan (2001) Perospirone. CNS Drugs 15:329337; discussion 338.

JE Overall , DR Gorham (1962) The brief psychiatric rating scale. Psychol Rep 10:799812.

D Piskulic , JS Olver , P Maruff , TR Norman (2009) Treatment of cognitive dysfunction in chronic schizophrenia by augmentation of atypical antipsychotics with buspirone, a partial 5-HT(1A) receptor agonist. Hum Psychopharmacol 24:437446.

T Sumiyoshi , Y Higuchi (2012) Facilitative effect of serotonin1A receptor agonists on cognition in patients with schizophrenia. Curr Med Chem 20:357362.

T Sumiyoshi , M Matsui , S Nohara , I Yamashita , M Kurachi , C Sumiyoshi , K Jayathilake , HY Meltzer (2001) Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment. Am J Psychiatry 158:17221725.

T Sumiyoshi , S Park , K Jayathilake , A Roy , A Ertugrul , HY Meltzer (2007) Effect of buspirone, a serotonin1A partial agonist, on cognitive function in schizophrenia: a randomized, double-blind, placebo-controlled study. Schizophr Res 95:158168.

T Sumiyoshi , CA Stockmeier , JC Overholser , GE Dilley , HY Meltzer (1996) Serotonin1A receptors are increased in postmortem prefrontal cortex in schizophrenia. Brain Res 708:209214.

J Tauscher , S Kapur , NP Verhoeff , DF Hussey , ZJ Daskalakis , S Tauscher-Wisniewski , AA Wilson , S Houle , S Kasper , RB Zipursky (2002) Brain serotonin 5-HT(1A) receptor binding in schizophrenia measured by positron emission tomography and [11C]WAY-100635. Arch Gen Psychiatry 59:514520.

DP Taylor , SL Moon (1991) Buspirone and related compounds as alternative anxiolytics. Neuropeptides 19 Suppl:1519.

K Wedzony , M Mackowiak , K Fijal , K Golembiowska (1996a) Evidence that conditioned stress enhances outflow of dopamine in rat prefrontal cortex: a search for the influence of diazepam and 5-HT1A agonists. Synapse 24:240247.

K Wedzony , M Mackowiak , K Fijal , K Golembiowska (1996b) Ipsapirone enhances the dopamine outflow via 5-HT1A receptors in the rat prefrontal cortex. Eur J Pharmacol 305:7378.

BD Winters , JM Reid (2010) A distributed cortical representation underlies crossmodal object recognition in rats. J Neurosci 30:62536261.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The The International Journal of Neuropsychopharmacology
  • ISSN: 1461-1457
  • EISSN: 1469-5111
  • URL: /core/journals/the-international-journal-of-neuropsychopharmacology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords: