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

Abstract

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.

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

“…This is likely due to the anticholinergic action149 and is a dangerous side effect which patients should be monitored for, given the reduced pain sensitivity demonstrated in schizophrenia 150,151. OLA, CLO, and low-potency FGAs substantially impair colon transit, while drugs with low affinity to cholinergic receptors, such as BRE, CAR, LUR, and PALI, do not 152.…”

Spatiotemporal Mapping Techniques Show Clozapine Impairs Neurogenic and Myogenic Patterns of Activity in the Colon of the Rabbit in a Dose-Dependent Manner

“…CIGH causes prolonged colonic transit (Baptista et al, 2015; Every-Palmer et al, 2016), with an array of clinical manifestations from constipation (Shirazi et al, 2016) to life-threatening conditions such as paralytic ileus (Nielsen and Meyer, 2012) and toxic megacolon (Palmer et al, 2008). Our work in identifying the likely underlying pharmacological mechanisms, leads us to recommend avoiding additional anticholinergic and antiserotenergic medication when using clozapine, using the lowest effective dose, and assertive management of slow transit.…”

Clozapine Induced Constipation: A Case Report.

“…Although a number of antipsychotics cause constipation, studies indicate Clozapine induced constipation is quite common and is "approximately three times more likely to occur than with other antipsychotics" [1]. Though constipation is not a serious side effect of Clozapine, reports state that if left undiagnosed and untreated, it may potentially prove to be fatal and cause death [4].…”