Current treatment strategies for clozapine-induced sialorrhea

OBJECTIVE: To provide an understanding of the underlying pathophysiology and current treatment options for clozapine-induced sialorrhea. DATA SOURCES: Literature was retrieved through MEDLINE (1977-February 2011) using the key search terms clozapine, sialorrhea, hypersalivation, drooling, and treatment. In addition, reference citations from identified publications were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles published in English identified from the data source were evaluated and included in the review. DATA SYNTHESIS: Sialorrhea is a common and disabling adverse effect of clozapine use. Current treatment options include topical and oral antimuscarinic medications and a-adrenergic agents. New areas of investigation include glycopyrrolate, botulinum toxin, and substitute benzamide derivatives. Thirteen clinical trials (2 retrospective, 5 open-label, 6 double-blind) and 13 case reports were reviewed. Overall, there are weak data on use of antimuscarinic agents, consisting mostly of small open-label or retrospective studies. Glycopyrrolate, however, demonstrated significant reduction of hypersalivation in a randomized controlled trial. Medications with activity at a-adrenergic receptors have shown positive results in case reports, retrospective evaluations, and an open-label trial, but have not been investigated in a double-blind, controlled fashion. Botulinum toxin also significantly improved sialorrhea in both a case report and double-blind study, although the trial included hypersalivation from other etiologies in addition to clozapine. Substitute benzamide derivatives have demonstrated significant improvements in randomized controlled trials; however, they are not available in the US. Overall, few treatment strategies have been evaluated in controlled settings, warranting further randomized controlled trials to identify more effective treatment options. CONCLUSIONS: Current pharmacologic treatment options for clozapine-induced sialorrhea are limited in number and efficacy. Although few randomized controlled trials have been conducted, this review identifies potential treatment alternatives for this common and sometimes severe adverse effect.