Rare and very rare adverse effects of clozapine

Abstract

Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment.

Update on the treatment of Parkinson’s disease psychosis: role of pimavanserin

“…This monitoring for agranulocytosis (an absolute neutrophil count below 500/mm 3 ) was initiated after a study in 1975. In this study, 17 of 2,660 (0.7%) patients were diagnosed with agranulocytosis, and 8 of these patients died from infection after diagnosis 26. It has been shown that agranulocytosis may occur at any dose; therefore, patients taking even the smaller doses used in PDP must be closely monitored.…”

An update of safety of clinically used atypical antipsychotics

“…Although it is the gold standard in the treatment of resistant schizophrenia with a clear and established superior effectiveness than other APs [66], clozapine has a wide range of AEs, many of which are severe or life-threatening, even if most of the latter are relatively rare [67].…”

“…The anticholinergic properties of clozapine as well as its H 1 antagonism were related to several grades of impairment of intestinal peristalsis ranging from transient-to-obstinate constipation and paralytic ileus up to intestinal obstruction [67]. Constipation is a very frequent reported AE (15%-60%) [98].…”

The Business Case for Expanded Clozapine Utilization

“…In the nonclozapine arm, it was assumed that ADRs did not occur and medications had no costs, so the costs reflected inpatient stays. Mortality was estimated by the effect of clozapine on suicide among veterans and anticipated mortality from serious ADRs (61)(62)(63). The business case for clozapine was broadened by multiplying the results over the treatment-eligible population within the VHA.…”

“…Pooled risks and mortality of the clozapine-related ADRs were calculated from studies identified through the literature review and the clozapine-prescribing information (7,(62)(63)(64). A pooled risk of clozapine-related seizures and subsequent risk of discontinuation were calculated from an analysis of the clozapine patient management system database (64).…”