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

Taro Kishi*, Herbert Y Meltzer, Nakao Iwata

*Corresponding author for this work

Research output: Contribution to journalReview article

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1259-1266
Number of pages8
JournalInternational Journal of Neuropsychopharmacology
Volume16
Issue number6
DOIs
StatePublished - Jul 1 2013

Fingerprint

Receptor, Serotonin, 5-HT1A
Antipsychotic Agents
Serotonin 5-HT1 Receptor Agonists
Meta-Analysis
Confidence Intervals
Psychopathology
Placebos
Schizophrenia
Odds Ratio
Buspirone
Controlled Clinical Trials
Therapeutics
PubMed
Libraries
Randomized Controlled Trials

Keywords

  • 5-HT receptor partial agonist
  • buspirone
  • discontinuation rate
  • efficacy
  • meta-analysis
  • psychosis
  • schizophrenia
  • systematic review
  • tandospirone

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Psychiatry and Mental health

Cite this

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title = "Augmentation of antipsychotic drug action by azapirone 5-HT1A receptor partial agonists: A meta-analysis",
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.{\^A} ={\^A} -0.46, CI{\^A} ={\^A} -0.79 to -0.13, p{\^A} ={\^A} 0.006, N{\^A} ={\^A} 4, n{\^A} ={\^A} 149) and marginally more effective to improve positive symptoms (s.m.d.{\^A} ={\^A} -0.31, CI{\^A} ={\^A} -0.64 to 0.01, p{\^A} ={\^A} 0.06, N{\^A} ={\^A} 4, n{\^A} ={\^A} 149). However, 5-HT1A partial agonists were not more efficacious than placebo as adjunctive therapy for improving negative symptoms (s.m.d.{\^A} ={\^A} -0.09, CI{\^A} ={\^A} -0.60 to 0.42, p{\^A} ={\^A} 0.72, N{\^A} ={\^A} 4, n{\^A} ={\^A} 149). In addition, there was no significant difference in discontinuation rates between 5-HT1A partial agonists and placebo (all cause: RR{\^A} ={\^A} 0.98, CI{\^A} ={\^A} 0.49-1.98, p{\^A} ={\^A} 0.96, N{\^A} ={\^A} 4, n{\^A} ={\^A} 153, side-effects: RR{\^A} ={\^A} 1.96, CI{\^A} ={\^A} 0.54-7.19, p{\^A} ={\^A} 0.31, N{\^A} ={\^A} 4, n{\^A} ={\^A} 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.",
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Augmentation of antipsychotic drug action by azapirone 5-HT1A receptor partial agonists : A meta-analysis. / Kishi, Taro; Meltzer, Herbert Y; Iwata, Nakao.

In: International Journal of Neuropsychopharmacology, Vol. 16, No. 6, 01.07.2013, p. 1259-1266.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Augmentation of antipsychotic drug action by azapirone 5-HT1A receptor partial agonists

T2 - A meta-analysis

AU - Kishi, Taro

AU - Meltzer, Herbert Y

AU - Iwata, Nakao

PY - 2013/7/1

Y1 - 2013/7/1

N2 - 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.

AB - 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.

KW - 5-HT receptor partial agonist

KW - buspirone

KW - discontinuation rate

KW - efficacy

KW - meta-analysis

KW - psychosis

KW - schizophrenia

KW - systematic review

KW - tandospirone

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