Therapeutic options in the treatment of clozapine-induced sialorrhea.

Clozapine is an effective atypical antipsychotic drug, but its use may be compromised by its side effects. Agranulocytosis may be fatal, but sialorrhea occurs more frequently and plays a major role in patients' noncompliance. A MEDLINE search from 1975-2000 revealed that treatment of clozapine-induced sialorrhea is predominantly based on case reports. Due to its elusive mechanism, physicians have attempted to treat this side effect with agents that counteract clozapine's adrenergic and muscarinic properties. We evaluated reported treatment options and other possible strategies from a pharmacologic standpoint. Antimuscarinic agents and alpha-receptor agonists are both viable 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 promising mechanism. Other selective, peripherally acting agents must be investigated in controlled clinical trials to determine their efficacy as possible alternatives.