Clozapine-induced sialorrhea: pathophysiology and management strategies

Abstract

Rationale: Clozapine is an atypical antipsychotic agent with proven efficacy in refractory schizophrenia, but its widespread use is limited by adverse effects such as agranulocytosis, seizures, sedation, weight gain, and sialorrhea. Clozapine-induced sialorrhea (CIS) is bothersome and has socially stigmatizing adverse effects, which result in poor treatment compliance. The pathophysiology of this condition is poorly understood and the treatment options available are based mostly on case reports and open-label studies. Objective: To review the available studies on CIS. Method: All relevant studies available through PUBMED search supplemented with manual search were undertaken. Result: The clinical features, complications, assessment, pathophysiology, and management of CIS are discussed. Conclusion: Although the studies evaluating the therapeutic options has limitations and no drug has been found to be superior, judicious use of pharmacological agents along with behavioral methods will reduce this troublesome side effect and enhance compliance.

Aripiprazole-Induced Sialorrhea Responsive to Amitriptyline Treatment

“…receptor but M1 and M4 are fewer than it is thought that the cause of antipsychotic-induced sialorrhea can be one of these; to involve α2-adrenergic antagonism, M4 muscarinic agonism or laryngeal peristalsis/ inhibition of swallowing reflex (2,12). In this case report, the most likely mechanism of aripiprazole induced sialorrhea is through central α2-adrenergic antagonism as reported with risperidone (13) and clozapine (2).…”

“…This is known as dose-related adverse effect (1). This condition may be particularly socially stigmatizing and troubling for patients, resulting in treatment nonadherence or discontinuation (2). Sialorrhea may emerge all day; however, its frequency and amount that is inversely proportional with ability to swallow, increases during sleep time (3).…”

“…Sialorrhea may emerge all day; however, its frequency and amount that is inversely proportional with ability to swallow, increases during sleep time (3). The patients frequently complain of awakening with a "wet pillow" (2).…”

Trihexyphenidyl (benzhexol) in clozapine-induced nocturnal enuresis and sialorrhea

“…[1] Clozapine-induced sialorrhea occurs at rates varying from 10 to 80% as reported in the literature. [2] Nocturnal enuresis is a less commonly reported side effect with a reported frequency varying from as little as 0.23% to as high as 41%. [3,4] We wish to report here a case of schizophrenia along with harmful use of cannabis, who developed both sialorrhea and enuresis while on clozapine, and who showed improvement in both the symptoms after receiving trihexiphenidyl.…”

“…[2] Drugs such as desmopressin, oxybutynin, and trihexyphenidyl have been helpful in clozapine-induced enuresis. [7] Caution needs to be observed while using a combination of trihexiphenidyl with clozapine as there may be an increase in anticholinergic effects as well as cognitive disturbances.…”