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Letter to the Editor   |    
Ketanserin Treatment of Tourette’s Syndrome in Children
CHRISTINE BONNIER, M.D.; MARIE-CÉCILE NASSOGNE, M.D.; PHILIPPE EVRARD, M.D.
Am J Psychiatry 1999;156:1122a-1123.

To the Editor: Gilles de la Tourette’s syndrome is a complex neurological disorder characterized by multiple motor and vocal tics, associated behavioral disturbances, and a chronic fluctuating course. Treatment of Tourette’s syndrome is often unsatisfactory, even with drugs such as haloperidol, pimozide, or clonidine, some of which carry the risk of serious adverse effects (1). Recently, risperidone, which combines highly potent serotonin 5-HT2 and potent dopamine antagonist properties, has been described to decrease motor and vocal tics in Tourette’s syndrome without major side effects (2, 3). Ketanserin is also a strong 5-HT2 antagonist and an α1-adrenergic agonist, but this drug’s activity with the dopamine receptor is 200 times weaker than that of haloperidol or risperidone (4, 5).

We investigated ketanserin treatment with seven children (four girls and three boys, 9 to 16 years of age) with Tourette’s syndrome conforming to DSM-III-R criteria. The children’s parents were fully orally informed about ketanserin and its potential side effects. Four children had received previous classical medications—haloperidol, pimozide, and clonidine principally—without improvement in two children, with relapse after 1 year in one child, and with relapse after 2 years in the fourth. Three other children received ketanserin as their first medication. Ke­tanserin was given in an initial dose of 20 mg/day. Six children showed a dramatic improvement within a few days. Total disappearance of tics was obtained with doses up to 240 mg/day (mean=120 mg/day). One boy withdrew from the study because of lack of response after 2 months. Ketanserin was stopped in one child after 4 months because of orthostatic hypotension. In two cases, tics re­appeared after 4 and 7 months despite higher doses. As for the three other children, one was lost to follow-up after 6 months, and two were still free of tics more than 1 year later.

To our knowledge, this is the first report of a clinical trial with ketanserin, a serotonergic antagonist, in children with Tourette’s syndrome. Our results confirm the important role of the serotonergic system in the pathogenesis of Tourette’s syndrome, although hypotension likely relates to its blockade of α1-adrenergic receptors; this may also play a role in the control of tics. On the basis of these trials, further controlled studies with selective 5-HT2 antagonists will be considered, especially in children.

Singer HS, Walkup JT: Tourette syndrome and other tic disorders: diagnosis, pathophysiology, and treatment. Medicine  1990; 70:15–32
 
Stamenkovic M, Aschauer H, Kasper S: Risperidone for Tourette’s syndrome. Lancet 1994; 344:1577–  1578
 
Bruun RD, Budman CL: Risperidone as a treatment for Tourette’s syndrome. J Clin Psychiatry  1996; 57:29–31
 
Leysen JE, Awouters F, Kennis L, Laduron PM, Vanderbeck J, Janssen PAJ: Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors. Life Sci 1981; 28:1015–  1022
 
Leysen JE, Gommeren W, Eens A, de Chaffoy de Courcelles D, Stoof JC, Janssen PAJ: Biochemical profile of risperidone, a new antipsychotic. J Pharmacol Exp Ther  1988; 247:661–670
[PubMed]
 
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References

Singer HS, Walkup JT: Tourette syndrome and other tic disorders: diagnosis, pathophysiology, and treatment. Medicine  1990; 70:15–32
 
Stamenkovic M, Aschauer H, Kasper S: Risperidone for Tourette’s syndrome. Lancet 1994; 344:1577–  1578
 
Bruun RD, Budman CL: Risperidone as a treatment for Tourette’s syndrome. J Clin Psychiatry  1996; 57:29–31
 
Leysen JE, Awouters F, Kennis L, Laduron PM, Vanderbeck J, Janssen PAJ: Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors. Life Sci 1981; 28:1015–  1022
 
Leysen JE, Gommeren W, Eens A, de Chaffoy de Courcelles D, Stoof JC, Janssen PAJ: Biochemical profile of risperidone, a new antipsychotic. J Pharmacol Exp Ther  1988; 247:661–670
[PubMed]
 
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