Colonic transit diagnostic test shows significant gastrointestinal hypomotility in clozapine-treated patients in comparison with subjects treated with other antipsychotics

Clozapine-Induced Gastrointestinal Hypomotility: A 22-Year Bi-National Pharmacovigilance Study of Serious or Fatal ‘Slow Gut’ Reactions, and Comparison with International Drug Safety Advice

“…This suggests constipation is not being recognized and treated seriously, despite the sometimes fatal consequences. This is consistent with other reports of low subjective awareness of objective hypomotility [5, 6, 38] and reinforces our earlier observation that clozapine-treated patients may not recognize or experience constipation in the same way as others due to changes in pain sensitivity or habituation, and thus may be less likely to complain [6, 38]. This decreased sensitivity places the responsibility for actively monitoring and treating CIGH on health professionals; yet the potential severity of CIGH remains poorly recognized amongst mental health staff [8, 15, 17, 39–41].…”

“…However, clozapine’s advantages come at a cost, with an array of problematic adverse effects of which clozapine-induced gastrointestinal hypomotility (CIGH) is one of the most serious [5, 6], albeit one that has received scant attention until the last decade.…”

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.…”

“…It has been shown to induce severe constipation, abdominal distension, ileus and intestinal obstruction and perforation, which can on occasion lead to death (Pelizza and La Pesa, 2007; Palmer et al, 2008; Hibbard et al, 2009; Every-Palmer et al, 2016). Further, therapeutic doses of clozapine are known to prolong colonic transit time (Baptista et al, 2015; Every-Palmer et al, 2016, 2017), an effect that is only partially ameliorated with assertive monitoring regimes and laxative treatment (Every-Palmer et al, 2017). While it is thought that disruption of colonic motility may affect between 50 and 80% of clozapine users (Baptista et al, 2015; Every-Palmer et al, 2016, 2017), with 30% experiencing constipation (Shirazi et al, 2016), and have a higher associated mortality rate than the better known adverse effect of agranulocytosis (Cohen et al, 2012), clozapine's gastrointestinal adverse effects remain poorly understood, under-recognized and inadequately researched (Flanagan and Ball, 2011; Every-Palmer et al, 2014).…”

Mild to moderate clozapine-induced gastrointestinal hypomotility should not require cessation of clozapine

“…However, the term CIGH was coined in 2008 2 and refers to the effects of clozapine in slowing transit throughout the gastrointestinal tract. [3][4][5][6][7] Clozapine impairs gut motility dramatically and this may result in an array of clinical presentations, from mild constipation and delayed gastric emptying at one end, to paralytic ileus, toxic megacolon and possibly death at the other. In other words, paralytic ileus and other lifethreatening complications of CIGH, conditions that necessitate urgent medical and possibly surgical intervention, are but a small sub-set of the CIGH spectrum Mild to moderate CIGH is very common, probably occurring in most people taking clozapine.…”