Treatment of Tourette?s Syndrome With Finasteride
MARCO BORTOLATO, M.D., Ph.D., ANTONELLA MURONI, M.D., and FRANCESCO MARROSU, M.D. Monserrato, Ital
Am J Psychiatry 164:1914-1915, December 2007
doi: 10.1176/appi.ajp.2007.07060978
Letters 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.[/I]
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.
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.
References
1. Peterson BS, Leckman JF, Scahill L, Naftolin F, Keefe D, Charest NJ, Cohen DJ: Steroid hormones and CNS sexual dimorphisms modulate symptom expression in Tourette"s syndrome. Psychoneuroendocrinology 1992; 17:553?563
2. Peterson BS, Zhang H, Anderson GM, Leckman JF: A double-blind, placebo-controlled, crossover trial of an antiandrogen in the treatment of Tourette"s syndrome. J Clin Psychopharmacol 1998; 18:324?331
3. Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A: Finasteride-induced depression: a prospective study. BMC Clin Pharmacol 2006; 6:7
MARCO BORTOLATO, M.D., Ph.D., ANTONELLA MURONI, M.D., and FRANCESCO MARROSU, M.D. Monserrato, Ital
Am J Psychiatry 164:1914-1915, December 2007
doi: 10.1176/appi.ajp.2007.07060978
Letters 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.[/I]
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.
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.
References
1. Peterson BS, Leckman JF, Scahill L, Naftolin F, Keefe D, Charest NJ, Cohen DJ: Steroid hormones and CNS sexual dimorphisms modulate symptom expression in Tourette"s syndrome. Psychoneuroendocrinology 1992; 17:553?563
2. Peterson BS, Zhang H, Anderson GM, Leckman JF: A double-blind, placebo-controlled, crossover trial of an antiandrogen in the treatment of Tourette"s syndrome. J Clin Psychopharmacol 1998; 18:324?331
3. Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A: Finasteride-induced depression: a prospective study. BMC Clin Pharmacol 2006; 6:7
