A double-blind, placebo-controlled, crossover trial of an antiandrogen in the treatment of Tourette's syndrome.
The objective of this study was to document the effects of androgen receptor blockade on tic and obsessive-compulsive symptoms in Tourette's syndrome (TS) patients. Thirteen adult TS subjects, 10 men and 3 women, completed 3 weeks of each phase of a double-blind, placebo-controlled, crossover trial of flutamide, a selective androgen receptor antagonist. Symptom severity ratings and hormone levels were obtained at each of the trial's six clinic visits. Flutamide was well-tolerated and produced a significant reduction in motor but not phonic tic symptom severity. It modestly improved symptoms of obsessive-compulsive disorder in the men who had this disorder. Changes in hormone levels during flutamide administration provided evidence for the existence of physiologic mechanisms that compensate for the blocking of the androgen receptor. The therapeutic effects of flutamide are modest in magnitude and they seem to be short-lived, possibly because of physiologic compensation for androgen receptor blockade. Given the potentially serious side effects of flutamide, the use of this agent in the treatment of tics should be reserved for patients who have relatively debilitating symptoms. The therapeutic and endocrine findings may have implications for understanding the sex differences in TS prevalence and the sex-specific variability in the phenotypic expression of the putative TS vulnerability genes.
General Clinical Research Center, Yale Child Study Center, Yale School of Medicine, New Haven, Connecticut 06520, USA. bradley.peterson@yale.edu
B S
BS
Peterson
H
H
Zhang
G M
GM
Anderson
J F
JF
Leckman
D000328:Adult; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005485:Flutamide / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000188:drug therapy; D005879:Tourette Syndrome / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
D000726:Androgen Antagonists; D005485:Flutamide