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Int. J. Mol. Sci. 2016, 17(6), 863; doi:10.3390/ijms17060863

Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis

GKT School of Medical Education Department, King’s College London University, London SE1 1UL, UK
Health Service and Population Research Department, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK
Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AZ, UK
Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London SE5 8AF, UK
National Psychosis Unit, South London and Maudsley NHS Foundation Trust, London BR3 3BX, UK
Toxicology Unit, Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK
Author to whom correspondence should be addressed.
Academic Editor: Domenico De Berardis
Received: 13 March 2016 / Revised: 13 May 2016 / Accepted: 16 May 2016 / Published: 2 June 2016
(This article belongs to the Special Issue Antipsychotics)
View Full-Text   |   Download PDF [728 KB, uploaded 2 June 2016]   |  


Constipation is a frequently overlooked side effect of clozapine treatment that can prove fatal. We conducted a systematic review and meta-analysis to estimate the prevalence and risk factors for clozapine-associated constipation. Two authors performed a systematic search of major electronic databases from January 1990 to March 2016 for articles reporting the prevalence of constipation in adults treated with clozapine. A random effects meta-analysis was conducted. A total of 32 studies were meta-analyzed, establishing a pooled prevalence of clozapine-associated constipation of 31.2% (95% CI: 25.6–37.4) (n = 2013). People taking clozapine were significantly more likely to be constipated versus other antipsychotics (OR 3.02 (CI: 1.91–4.77), p < 0.001, n = 11 studies). Meta-regression identified two significant study-level factors associated with constipation prevalence: significantly higher (p = 0.02) rates of constipation were observed for those treated in inpatient versus outpatient or mixed settings and for those studies in which constipation was a primary or secondary outcome measure (36.9%) compared to studies in which constipation was not a specified outcome measure (24.8%, p = 0.048). Clozapine-associated constipation is common and approximately three times more likely than with other antipsychotics. Screening and preventative strategies should be established and appropriate symptomatic treatment applied when required. View Full-Text
Keywords: constipation; clozapine; treatment-resistant schizophrenia; adverse events; systematic review; meta-analysis constipation; clozapine; treatment-resistant schizophrenia; adverse events; systematic review; meta-analysis

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Shirazi, A.; Stubbs, B.; Gomez, L.; Moore, S.; Gaughran, F.; Flanagan, R.J.; MacCabe, J.H.; Lally, J. Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2016, 17, 863.

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