We would like to counter the suggestion to use benztropine or clonidine as a means to control clozapine-induced hypersalivation as suggested in “Reducing clozapine-induced hypersalivation” (Pearls, Current Psychiatry, October 2011, p. 77-78).
As stated in the article, clozapine is an antagonist for all known muscarinic receptors except M4—where it is an agonist—making it a potent anticholinergic medication with the potential to cause excessive saliva production.1,2 Another proposed mechanism for clozapine-induced hypersalivation is its antagonist activity at α-1 receptors, thus the suggestion to use clonidine to combat this side effect. The use of benztropine, another medication with known anticholinergic activity, or clonidine, a medication that may cause additional hypotension, to treat clozapine-induced hypersalivation may cause further unwanted complications and may not be the best option to treat this troubling side effect.
We have had great success locally using medications such as atropine or ipratropium as first-line treatments for clozapine-induced hypersalivation in an effort to minimize additional systemic side effects, such as those seen with benztropine and clonidine. Atropine eye drops administered orally, starting with 1 drop and titrated up to 2 drops twice daily to adequate response, has been shown to be successful according to patient opinion in several case reports.3 Alternatively, intranasal ipratropium orally administered 1 to 2 sprays, up to 3 times daily has shown improvement in clozapine-induced hypersalivation according to patient report.3 Although controlled trials to support the use of topical treatment for clozapine-induced hypersalivation are necessary, attempting to minimize additional adverse effects warrants a trial of atropine or ipratropium before using systemically acting medications such as benztropine or clonidine.
Sarah Hutfilz, PharmD
PGY1 Pharmacy Practice Resident
Department of Pharmacy
University of North Carolina Hospitals and Clinics
Clinical Instructor
University of North Carolina
Eshelman School of Pharmacy
Shauna Garris, PharmD, BCPP
Neurology/Psychiatry Clinical Specialist
Department of Pharmacy
University of North Carolina Hospitals and Clinics
Clinical Assistant Professor
University of North Carolina
Eshelman School of Pharmacy
M. Lindsey Kennedy, PharmD, BCPS, BCPP
Psychiatry Clinical Specialist
Department of Pharmacy
University of North Carolina Hospitals and Clinics
Clinical Assistant Professor
University of North Carolina School
of Medicine
University of North Carolina
Eshelman School of Pharmacy
Chapel Hill, NC
The authors respond
We thank Drs. Hutfilz, Garris, and Kennedy for their response and comments. We acknowledge that the medications we suggested have potentially harmful adverse effects; however, they are evidence-based. Atropine eye drops and ipratropium are interesting suggestions; if their use is based on evidence, they should have been included in the article.
We agree that further studies may show these topical approaches to be superior, but our recommendation, based on the best evidence available from the clinical studies, would be to use medications that have been studied while advocating for further study of medications with a theoretical superiority that is not yet proven.
Gurprit Lamba, MD
Geriatric Psychiatry Fellow
Partners HealthCare Geriatric Psychiatry Fellowship
Boston, MA
James M. Ellison, MD, MPH
Associate Professor of Psychiatry
Harvard Medical School
Boston, MA