Therapeutic options in the treatment of clozapine-induced sialorrhea

Clozapine is an effective atypical antipsychotic drug, but its use may be c ompromised by its side effects. Agranulocytosis may be fatal, but sialorrhe a occurs more frequently and plays a major role in patients' noncompliance. A MEDLINE search from 1975-2000 revealed that treatment of clozapine-induc ed sialorrhea is predominantly based on case reports. Due to its elusive me chanism, physicians have attempted to treat this side effect with agents th at counteract clozapine's adrenergic and muscarinic properties. We evaluate d reported treatment options and other possible strategies from a pharmacol ogic standpoint. Antimuscarinic agents and or-receptor agonists are both vi able options but must be administered and monitored cautiously in patients with psychiatric disorders. Although not yet available in the United States , pirenzepine, a selective muscarinic receptor antagonist, has the most pro mising mechanism. Other selective, peripherally acting agents must be inves tigated in controlled clinical trials to determine their efficacy as possib le alternatives.