March 2010

Treating Persistent Insomnia: Therapy, Meds, or Both?
While cognitive behavioral therapy is probably best for long-term treatment of chronic insomnia, hypnotics can add benefits acutely.

Diet and Depression
Overall dietary pattern may be more important than individual components (such as omega-3 fatty acids) in lowering the risk of depression.

In Brief
Another Negative Trial of Ginkgo biloba for Cognitive Decline; Physical Activity during Pregnancy Has Mixed Results on Postpartum Depression

Carotidynia Associated with SSRIs
Carotidynia may be a rare side effect of selective serotonin reuptake inhibitors and might be more common in migraine sufferers.

Clozapine Hypersalivation: A Negative Study with Ipratropium
In a small, double-blind trial, ipratropium (Atrovent and others) was not effective in decreasing sialorrhea associated with clozapine (Clozaril and others) treatment.

Clozapine Hypersalivation: A Negative Study with Ipratropium

March 2010

More than half of patients who take clozapine (Clozaril and others) awaken each morning to a soaked pillow. Not only is hypersalivation (sialorrhea) unpleasant, it may cause aspiration pneumonia, swollen salivary glands, and skin irritation. Anticholinergic agents are frequently employed as attempted antidotes, but peripheral anticholinergic effects can be limiting or even severe, such as ileus. What's more, anticholinergic agents that enter the brain impair memory.

Ipratropium (Atrovent and others) is an anticholinergic compound prescribed for allergic rhinitis and rhinorrhea. Administered intranasally, it has minimal central nervous system absorption. Anecdotes and open-label series suggest it may be effective for clozapine-induced hypersalivation. Sockalingam and associates conducted a randomized, double-blind, placebo-controlled crossover study to follow up on these observations.1

Twenty patients with clozapine-induced hypersalivation participated in this 5- to 6-week trial, funded by Novartis. Each subject took sublingual ipratropium or placebo at bedtime for 2 weeks. After a 1- or 2-week washout interval, subjects then took the alternate treatment for another 2 weeks.

Bottom line: it didn't work. There was no difference in the amount of hypersalivation between ipratropium and placebo treatment.

Where does this leave patients with troublesome sialorrhea due to clozapine? Despite this negative study, some patients might, in fact, benefit from ipratropium or other anticholinergic agents. Alternatively, limited data suggest that α-adrenergic drugs, such as clonidine (Catapres and others) or guanfacine (Tenex and others), may help. But scientific proof of safety and efficacy for any antidote is sadly lacking, and once again, the clinician-patient team is left to trial and error.

1Sockalingam S, Shammi C, Remington G: Treatment of clozapine-induced hypersalivation with ipratropium bromide: A randomized, double-blind, placebo-controlled crossover study. J Clin Psychiatry 2009;70:1114-1119.