Is clonidine useful for treatment of clozapine-induced sialorrhea?

Clozapine has shown superior efficacy in treatment of refractory schizophrenia, but its use is limited by emergent side-effects. Among other adverse effects, sialorrhea is a troublesome side-effect, its stigmatizing nature results in poor treatment compliance. Several hypotheses have been put forward in the etiology of clozapine-induced sialorrhea. α₂ adrenergic antagonism is hypothesized to be involved in its pathophysiology, based on the response to clonidine and lofexidine. Oral clonidine (50 to 100 μg/day) was tried on 12 stable outpatients of schizophrenia maintained on clozapine. Wet area over the pillow as reported by the patients was recorded at baseline and at 4 weeks of treatment along with the subjective response after the treatment. Most of the patients reported a decrease in sialorrhea without any adverse events. We describe encouraging results in an open case series of oral clonidine for clozapine-induced sialorrhea.