title: Current treatment strategies for clozapine-induced sialorrhea.
abstract: OBJECTIVE
  To provide an understanding of the underlying pathophysiology and current treatment options for clozapine-induced sialorrhea.
  
  
  METHODS
  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.
  
  
  METHODS
  All articles published in English identified from the data source were evaluated and included in the review.
  
  
  RESULTS
  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.
authors.affiliation: College of Pharmacy, The University of Texas, Austin, TX.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Bird
authors.forename: Tawny L
authors.initials: TL
authors.lastname: Smith
authors.forename: Amy E
authors.initials: AE
authors.lastname: Walton
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003024:Clozapine / Q000009:adverse effects*; D004311:Double-Blind Method; D006801:Humans; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D012189:Retrospective Studies; D012798:Sialorrhea / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000316:Adrenergic alpha-Agonists; D018727:Muscarinic Antagonists; D003024:Clozapine