Clozapine-induced hypersalivation: a review of treatment strategies

Can J Psychiatry. 2007 Jun;52(6):377-84. doi: 10.1177/070674370705200607.


Objective: Clozapine-induced hypersalivation (CIH) is a significant side effect affecting about one-third of patients treated with clozapine. CIH can be stigmatizing, can affect quality of life, and can result in discontinuation of clozapine treatment. The purpose of this review is to provide an understanding of CIH, specifically, its pathophysiology, measurement, and the evidence for CIH treatment alternatives.

Methods: We searched MEDLINE from 1980 to June 2006 for all reported pharmacologic treatment studies related to CIH. We identified additional references by a manual search of the bibliographies of retrieved articles.

Results: Several studies reported improvement of CIH with both selective and nonselective anticholinergic medications. However, with the exception of local anticholinergic agents such as ipratropium bromide and atropine eye drops, potential systemic adverse effects limit the effectiveness of this class of medications. Open-label studies of clonidine, an alpha2 antagonist, suggest that it may be beneficial in managing CIH. Other pharmacologic treatments, such as amisulpride and botulinum toxin, may be useful in refractory CIH cases.

Conclusion: Although few randomized controlled trials were found in the literature, this review highlights potential treatment alternatives for this common and disabling cause of hypersalivation. Prompt and effective treatment of CIH may assist with treatment tolerability, adherence, and outcomes in patients with treatment-refractory schizophrenia. Information on funding and support and author affiliations appears at the end of the article.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Clozapine / adverse effects*
  • Humans
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / epidemiology*
  • Sialorrhea / chemically induced*
  • Sialorrhea / epidemiology*
  • Stereotyping


  • Clozapine