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 α-
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 α-
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.