Adjunctive ondansetron for schizophrenia: A systematic review and meta-analysis of randomized controlled trials

Wei Zheng, Dong Bin Cai, Qing E. Zhang, Jie He, Li Yun Zhong, Kang Sim, Gabor S. Ungvari, Yu Ping Ning, Yu Tao Xiang

Research output: Contribution to journalReview article

Abstract

The serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor has been implicated in the pathogenesis of schizophrenia. This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive ondansetron, a potent 5-HT3 receptor antagonist, in the treatment of schizophrenia. Only RCTs examining adjunctive ondansetron for schizophrenia were included. Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were analyzed using RevMan, Version 5.3. Study quality was evaluated with the Cochrane risk of bias and the Jadad scale. Data of 5 RCTs (n = 304) covering 149 patients on ondansetron (4-8 mg/day) and 155 patients on placebo were analyzed. Three RCTs reported “randomized allocation” with a specific description; the weighted Jadad score was 3.8. Adjunctive ondansetron outperformed placebo in the reduction of Positive and Negative Syndrome Scale (PANSS) total score [3 RCTs, n = 171; SMD: −1.06 (95%CI: −2.10, −0.02), p = 0.04, I 2 = 85%], the negative [4 RCTs, n = 209; SMD: −0.96 (95%CI: −1.71, −0.22), p = 0.01, I 2 = 80%], and general psychopathology symptom scores [3 RCTs, n = 171; SMD: −0.97 (95%CI: −1.91, −0.02), p = 0.04, I 2 = 82%], but not in the positive (p = 0.05) and depressive symptom scores (p = 0.91). The difference in PANSS total score remained significant after excluding one outlying RCT [2 RCTs, n = 141; SMD: −0.50 (95%CI: −0.84, −0.16), P = 0.004, I 2 = 0%]. Four RCTs examined the effect of ondansetron on cognition applying different instruments yielding conflicting findings. Ondansetron was superior over placebo in improving extrapyramidal symptoms, but no group differences were found in overall discontinuation rate and adverse drug reactions. In conclusion, adjunctive ondansetron appears to be efficacious and safe in improving negative symptoms and general psychopathology. The effect of ondansetron on cognitive impairment in schizophrenia needs to be further explored in large-scale RCTs.

Original languageEnglish
Pages (from-to)27-33
Number of pages7
JournalJournal of Psychiatric Research
Volume113
DOIs
Publication statusPublished - 1 Jun 2019

Fingerprint

Ondansetron
Meta-Analysis
Schizophrenia
Randomized Controlled Trials
Confidence Intervals
Receptors, Serotonin, 5-HT3
Placebos
Psychopathology
Drug-Related Side Effects and Adverse Reactions
Cognition
Serotonin
Odds Ratio

Cite this

Zheng, Wei ; Cai, Dong Bin ; Zhang, Qing E. ; He, Jie ; Zhong, Li Yun ; Sim, Kang ; Ungvari, Gabor S. ; Ning, Yu Ping ; Xiang, Yu Tao. / Adjunctive ondansetron for schizophrenia : A systematic review and meta-analysis of randomized controlled trials. In: Journal of Psychiatric Research. 2019 ; Vol. 113. pp. 27-33.
@article{b88841cac36e4c67abf34ad62867f858,
title = "Adjunctive ondansetron for schizophrenia: A systematic review and meta-analysis of randomized controlled trials",
abstract = "The serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor has been implicated in the pathogenesis of schizophrenia. This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive ondansetron, a potent 5-HT3 receptor antagonist, in the treatment of schizophrenia. Only RCTs examining adjunctive ondansetron for schizophrenia were included. Standardized mean difference (SMD), risk ratio (RR) and their 95{\%} confidence intervals (CIs) were analyzed using RevMan, Version 5.3. Study quality was evaluated with the Cochrane risk of bias and the Jadad scale. Data of 5 RCTs (n = 304) covering 149 patients on ondansetron (4-8 mg/day) and 155 patients on placebo were analyzed. Three RCTs reported “randomized allocation” with a specific description; the weighted Jadad score was 3.8. Adjunctive ondansetron outperformed placebo in the reduction of Positive and Negative Syndrome Scale (PANSS) total score [3 RCTs, n = 171; SMD: −1.06 (95{\%}CI: −2.10, −0.02), p = 0.04, I 2 = 85{\%}], the negative [4 RCTs, n = 209; SMD: −0.96 (95{\%}CI: −1.71, −0.22), p = 0.01, I 2 = 80{\%}], and general psychopathology symptom scores [3 RCTs, n = 171; SMD: −0.97 (95{\%}CI: −1.91, −0.02), p = 0.04, I 2 = 82{\%}], but not in the positive (p = 0.05) and depressive symptom scores (p = 0.91). The difference in PANSS total score remained significant after excluding one outlying RCT [2 RCTs, n = 141; SMD: −0.50 (95{\%}CI: −0.84, −0.16), P = 0.004, I 2 = 0{\%}]. Four RCTs examined the effect of ondansetron on cognition applying different instruments yielding conflicting findings. Ondansetron was superior over placebo in improving extrapyramidal symptoms, but no group differences were found in overall discontinuation rate and adverse drug reactions. In conclusion, adjunctive ondansetron appears to be efficacious and safe in improving negative symptoms and general psychopathology. The effect of ondansetron on cognitive impairment in schizophrenia needs to be further explored in large-scale RCTs.",
keywords = "Cognition, Meta-analysis, Negative symptoms, Ondansetron, Schizophrenia",
author = "Wei Zheng and Cai, {Dong Bin} and Zhang, {Qing E.} and Jie He and Zhong, {Li Yun} and Kang Sim and Ungvari, {Gabor S.} and Ning, {Yu Ping} and Xiang, {Yu Tao}",
year = "2019",
month = "6",
day = "1",
doi = "10.1016/j.jpsychires.2019.02.024",
language = "English",
volume = "113",
pages = "27--33",
journal = "Journal of Psychiatric Research",
issn = "0022-3956",
publisher = "Elsevier",

}

Adjunctive ondansetron for schizophrenia : A systematic review and meta-analysis of randomized controlled trials. / Zheng, Wei; Cai, Dong Bin; Zhang, Qing E.; He, Jie; Zhong, Li Yun; Sim, Kang; Ungvari, Gabor S.; Ning, Yu Ping; Xiang, Yu Tao.

In: Journal of Psychiatric Research, Vol. 113, 01.06.2019, p. 27-33.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Adjunctive ondansetron for schizophrenia

T2 - A systematic review and meta-analysis of randomized controlled trials

AU - Zheng, Wei

AU - Cai, Dong Bin

AU - Zhang, Qing E.

AU - He, Jie

AU - Zhong, Li Yun

AU - Sim, Kang

AU - Ungvari, Gabor S.

AU - Ning, Yu Ping

AU - Xiang, Yu Tao

PY - 2019/6/1

Y1 - 2019/6/1

N2 - The serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor has been implicated in the pathogenesis of schizophrenia. This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive ondansetron, a potent 5-HT3 receptor antagonist, in the treatment of schizophrenia. Only RCTs examining adjunctive ondansetron for schizophrenia were included. Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were analyzed using RevMan, Version 5.3. Study quality was evaluated with the Cochrane risk of bias and the Jadad scale. Data of 5 RCTs (n = 304) covering 149 patients on ondansetron (4-8 mg/day) and 155 patients on placebo were analyzed. Three RCTs reported “randomized allocation” with a specific description; the weighted Jadad score was 3.8. Adjunctive ondansetron outperformed placebo in the reduction of Positive and Negative Syndrome Scale (PANSS) total score [3 RCTs, n = 171; SMD: −1.06 (95%CI: −2.10, −0.02), p = 0.04, I 2 = 85%], the negative [4 RCTs, n = 209; SMD: −0.96 (95%CI: −1.71, −0.22), p = 0.01, I 2 = 80%], and general psychopathology symptom scores [3 RCTs, n = 171; SMD: −0.97 (95%CI: −1.91, −0.02), p = 0.04, I 2 = 82%], but not in the positive (p = 0.05) and depressive symptom scores (p = 0.91). The difference in PANSS total score remained significant after excluding one outlying RCT [2 RCTs, n = 141; SMD: −0.50 (95%CI: −0.84, −0.16), P = 0.004, I 2 = 0%]. Four RCTs examined the effect of ondansetron on cognition applying different instruments yielding conflicting findings. Ondansetron was superior over placebo in improving extrapyramidal symptoms, but no group differences were found in overall discontinuation rate and adverse drug reactions. In conclusion, adjunctive ondansetron appears to be efficacious and safe in improving negative symptoms and general psychopathology. The effect of ondansetron on cognitive impairment in schizophrenia needs to be further explored in large-scale RCTs.

AB - The serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor has been implicated in the pathogenesis of schizophrenia. This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive ondansetron, a potent 5-HT3 receptor antagonist, in the treatment of schizophrenia. Only RCTs examining adjunctive ondansetron for schizophrenia were included. Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were analyzed using RevMan, Version 5.3. Study quality was evaluated with the Cochrane risk of bias and the Jadad scale. Data of 5 RCTs (n = 304) covering 149 patients on ondansetron (4-8 mg/day) and 155 patients on placebo were analyzed. Three RCTs reported “randomized allocation” with a specific description; the weighted Jadad score was 3.8. Adjunctive ondansetron outperformed placebo in the reduction of Positive and Negative Syndrome Scale (PANSS) total score [3 RCTs, n = 171; SMD: −1.06 (95%CI: −2.10, −0.02), p = 0.04, I 2 = 85%], the negative [4 RCTs, n = 209; SMD: −0.96 (95%CI: −1.71, −0.22), p = 0.01, I 2 = 80%], and general psychopathology symptom scores [3 RCTs, n = 171; SMD: −0.97 (95%CI: −1.91, −0.02), p = 0.04, I 2 = 82%], but not in the positive (p = 0.05) and depressive symptom scores (p = 0.91). The difference in PANSS total score remained significant after excluding one outlying RCT [2 RCTs, n = 141; SMD: −0.50 (95%CI: −0.84, −0.16), P = 0.004, I 2 = 0%]. Four RCTs examined the effect of ondansetron on cognition applying different instruments yielding conflicting findings. Ondansetron was superior over placebo in improving extrapyramidal symptoms, but no group differences were found in overall discontinuation rate and adverse drug reactions. In conclusion, adjunctive ondansetron appears to be efficacious and safe in improving negative symptoms and general psychopathology. The effect of ondansetron on cognitive impairment in schizophrenia needs to be further explored in large-scale RCTs.

KW - Cognition

KW - Meta-analysis

KW - Negative symptoms

KW - Ondansetron

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=85063323407&partnerID=8YFLogxK

U2 - 10.1016/j.jpsychires.2019.02.024

DO - 10.1016/j.jpsychires.2019.02.024

M3 - Review article

VL - 113

SP - 27

EP - 33

JO - Journal of Psychiatric Research

JF - Journal of Psychiatric Research

SN - 0022-3956

ER -