Treatment of Tourette’s Syndrome With Finasteride
To the Editor: The marked male predominance of Tourette’s syndrome suggests that androgens may play a key role in the pathophysiology of this disorder (1) . Accordingly, androgen receptor antagonists, such as flutamide, significantly attenuate Tourette’s syndrome symptoms (2) , yet their efficacy is hindered by severe side effects. A valid alternative to reduce androgen brain signaling may be afforded by inhibitors of 5-alpha-reductase (5-AR), the main rate-limiting enzyme in androgen metabolism. Thus, we tested the efficacy of finasteride, the prototypical 5-AR inhibitor, in a Tourette’s syndrome patient who was unresponsive to traditional therapy. Finasteride is approved for the treatment of benign prostatic hyperplasia and alopecia; it is psychoactive (3) and produces very limited side effects.
A 34-year-old man with a 25-year history of severe Tourette’s syndrome was referred to our service following a precipitation of his clinical conditions. His symptoms included self-injuring motor tics (i.e., glass smashing and knuckle rubbing against rough surfaces), explosive bouts of complex vocalizations, stereotyped coprolalic utterances, ritual behaviors, aggressive and contamination-theme obsessions, cleaning and checking compulsions, and excessive sexual drive. Magnetic resonance imaging and laboratory tests were normal. His current treatment—initiated 2 years before and included pimozide (4 mg/day), clomipramine (37.5 mg/day), chlorpromazine (25 mg/day), and lorazepam (7.5 mg/day)—had only resulted in a transient, slight decrease of motoric compulsions and anxiety. After obtaining informed consent, we added finasteride (5 mg/day) to his current treatment and periodically assessed his symptoms by means of the Yale Global Tic Severity Scale and Yale-Brown Obsessive Compulsive Scale.
Finasteride gradually reduced both motor and phonic tics. Because of a misunderstanding about the regimen duration, the patient discontinued treatment at week 18. Three days later, he called our service complaining of a dramatic exacerbation in Tourette’s syndrome symptoms. Notably, the prompt reinstatement of finasteride led to a clear clinical improvement. After 28 weeks of treatment, finasteride led to a dramatic reduction in Yale Global Tic Severity Scale ( Figure 1 ) and Yale-Brown Obsessive Compulsive Scale scores (obsessive score: 58.3% initial values; compulsive score: 38.4% initial values). The patient also reported a normalized sex drive, enhanced mood and life quality, and no untoward effects.
a Yale Global Tic Severity Scale scores of total severity, total phonic tics, and total motor tics during the first 28 weeks of therapy.
In humans, finasteride inhibits mainly the isozyme 5-AR2, the activity of which is potently enhanced by androgens in the adult brain. Abnormal levels of brain 5-AR2 androgens, such as the potent neuroactive androgen dihydrotestosterone, may contribute to Tourette’s syndrome pathophysiology. Further studies, including double-blind clinical trials, are needed to fully evaluate the therapeutic potential of finasteride in Tourette’s syndrome.
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