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Intraoral application of atropine sulfate ophthalmic solution for clozapine-induced sialorrhea

PGY III Creighton—Nebraska Psychiatry Residency Program Department of Psychiatry 985578 Nebraska Medical Center Omaha, Nebraska 68198-5578 fax 402/354-6801 doctorsharma{at}hotmail.com

Sriram Ramaswamy, MD

PGY III Creighton—Nebraska Psychiatry Residency Program Department of Psychiatry Nebraska Medical Center

Elizabeth Dahl, MD

Assistant Professor Department of Psychiatry University of Nebraska Medical Center

Vijay Dewan, MD

Assistant Professor Department of Psychiatry University of Nebraska Medical Center

Published Online, July 13, 2004. www.theannals.com, DOI 10.1345/aph.1E077

Case Report. A 55-year-old African American man with a 23-year history of chronic paranoid schizophrenia presented to the clozapine clinic for his bimonthly visit. His medical history was significant for gastroesophageal reflux disease, for which he was taking ranitidine 150 mg twice a day. He is a nonsmoker and nonalcoholic, with no recent illicit drug use. The patient had been last hospitalized 5 years earlier in a long-term inpatient facility for exacerbation of his symptoms that included bizarre behavior, paranoid thoughts, and auditory hallucinations. During the hospitalization, he failed to respond to trials of haloperidol and chlorpromazine and was subsequently prescribed clozapine, with the dose titrated to 350 mg at bedtime. His positive symptoms of schizophrenia were in remission. However, he developed sialorrhea soon after the initiation of clozapine. The sialorrhea was attributed to clozapine, as the only other medication he was taking at that time was ranitidine and no medication change was made during the time of the onset of sialorrhea. The sialorrhea worsened at night, affecting the patient's sleep and quality of life. He rated the sialorrhea as moderate in severity.

Considering the schizophrenia treatment refractory, we decided to treat the man for sialorrhea rather than changing the schizophrenia medication. The patient was advised to swish 2 drops of atropine sulfate ophthalmic solution 1% in his mouth twice daily and then swallow it after a few seconds. Within 2 weeks, the patient reported a decrease in hypersalivation and no other adverse effects due to the atropine solution. Since then, he has been using the atropine ophthalmic solution intraorally, with complete resolution of sialorrhea.

Discussion. Although the exact mechanism of clozapine-induced sialorrhea is unknown, 2 hypotheses include stimulation of the M₄ muscarinic receptors located on the submandibular glands by clozapine, which has been suggested to increase salivary secretion, and a disturbance in deglutition combined with increased salivary secretion.^3,4 Atropine is a competitive antagonist of acetylcholine at the muscarinic receptors.⁵ This could theoretically explain its therapeutic efficacy in treating clozapine-induced sialorrhea. Although atropine poses the potential for additive anticholinergic effects with clozapine, it was well tolerated by our patient and we observed very few effects that could be due to systemic absorption of atropine. Thus, oral use of 1% atropine sulfate ophthalmic solution may be a safe, efficacious treatment for clozapine-induced sialorrhea. Several other agents that have been used in clozapine-induced sialorrhea include clonidine, terazosin, amitriptyline, and benztropine.² Further large-scale studies are needed to corroborate the findings of this case.

References

1. Safferman AZ, Kane JM, Aronowitz JS, Gordon MF, Pollack S, Lieberman JA. The use of clozapine in neurologic disorders. J Clin Psychiatry 1994;55(suppl B):98 -101.[Medline]
2. Rogers DP, Shramko JK. Therapeutic options in the treatment of clozapine-induced sialorrhea. Pharmacotherapy 2000;20:1092-5.[Medline]
3. Zorn SH, Jones SB, Ward KM, Liston DR. Clozapine is a potent and selective muscarinic M₄ receptor agonist. Eur J Pharmacol 1994;269:R1-2.[CrossRef][Medline]
4. Reinstein MJ, Sirovskaya LA, Chasanov MA, Jones LE, Sangarapillai M. Comparative efficacy and tolerability of benztropine and terazosin in the treatment of hypersalivation secondary to clozapine. Clin Drug Invest 1999;17:97-102.
5. Brown JH, Taylor P. Muscarinic receptor agonists and antagonists. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG, eds.Goodman & Gilman's the pharmacological basis of therapeutics . 9th ed. New York: McGraw-Hill, 1996:149 .

This Article PDF Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sharma, A. Articles by Dewan, V. Search for Related Content PubMed PubMed Citation Articles by Sharma, A. Articles by Dewan, V.