Treatment of clozapine-induced hypersalivation with ipratropium bromide: a randomized, double-blind, placebo-controlled crossover study.
OBJECTIVE
Clozapine-induced hypersalivation (CIH) occurs in up to 57% of treated patients and can be the source of considerable subjective distress. Previous open-label studies suggest that sublingual ipratropium bromide may be effective in treating CIH.


METHODS
We conducted a randomized, double-blind, placebo-controlled crossover trial to evaluate the efficacy of ipratropium in 20 individuals with CIH between September 2006 and August 2007. This study was 5 to 6 weeks in duration, based on the participants' clozapine blood-monitoring schedule, and it consisted of two 2-week crossover phases separated by a 1- or 2-week washout period. Primary outcome measures included the reduction in the Toronto Nocturnal Hypersalivation Scale (TNHS) and the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales. Secondary outcomes included visual analog scales assessing hypersalivation severity (VAS-S) and distress (VAS-D).


RESULTS
No significant reduction in CIH was found on the TNHS (P = .379), CGI-S (P = .266), or CGI-I (P = .599). Moreover, no difference was noted between study groups on the VAS-S (P = .969) and VAS-D (P = .527). There was no difference in the number of CIH responders at the conclusion of the 2-week placebo (40%, n = 8) and ipratropium (45%, n = 9) study phases (45%, n = 9) according to the TNHS. Randomization order did not have a significant effect on TNHS, CGI-S, or CGI-I scores. Tolerability was comparable between groups, with dry mouth occurring in 1 placebo group subject and 2 ipratropium group subjects.


CONCLUSIONS
Despite the reports of some preliminary studies that ipratropium is an efficacious treatment for CIH, ipratropium failed to demonstrate significant clinical effect in comparison to placebo. Further research should explore the efficacy of other locally acting anticholinergic agents or other classes of medications.


BACKGROUND
clinicaltrials.gov Identifier: NCT00381589.
Sockalingam
Sanjeev
S
University Health Network, Toronto General Hospital 8EN-225, 200 Elizabeth St, Toronto, Ontario M5G 2C4, Canada. sanjeev.sockalingam@uhn.on.ca
Shammi
Chekkera
C
Remington
Gary
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D003024:Clozapine / Q000009:adverse effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D009241:Ipratropium / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000188:drug therapy; D012559:Schizophrenia / Q000188:drug therapy; D012720:Severity of Illness Index; D012798:Sialorrhea / Q000139:chemically induced* / Q000188:drug therapy*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D018680:Cholinergic Antagonists; D009241:Ipratropium; D003024:Clozapine