Aripiprazole and Tourette syndrome

LETTERS TO THE EDITORS

Aripiprazole and Tourette syndrome

Ana G Hounie; Maria Alice De Mathis; Aline S Sampaio; Marcos T Mercadante

PROTOC - Obsessive spectrum disorders Project- Department of Psychiatry - University of São Paulo

Dear Editor,

Tourette syndrome (TS) is characterized by chronic motor and vocal tics. In the '60s, neuroleptics have started to be used on TS and became the most efficient medications. Most used neuroleptics which have been reported in controlled studies or case reports are haloperidol, pimozide, sulpiride, risperidone, olanzapine and ziprazidone.¹ Since then, typical neuroleptics have been decreasingly prescribed due to their side-effects. We will present a resistant TS case that responded with aripiprazol, whose mechanism of action differs from both typical and atypical antipsycotics.² Up to now, there is no publications about aripiprazol on TS.

P., 20 years old, male, single, student, born at the countryside of the state of São Paulo and living at the state's capital, has had his first multiple motor and vocal tics since the age of five. These tics have increasingly worsened causing much suffering for the patient and his family. Additionally, the patient showed obsessive-compulsive symptoms, besides major depressive episode, separation anxiety and panic with agoraphobia. He has unsuccessfully undergone all conventional (haloperidol, pimozide, trifluoperazine, sulpiride, olanzapine, ziprazidone, clonidine, botulinum toxin) and alternative (pergolide, nicotine, clonazepan, reserpine) tics treatments without success. It was added aripiprazol (15 mg/day) to the previous scheme a (sertraline + olanzapine, the latter gradually withdrawn) with tic improvement. Improvement was observed since the second week onwards using the medication and has persisted after three months of continuous treatment with 15 mg/day.

The floating nature of tics hampers to assess if the improvement occurred due to the medication or to a remission phase of the disease proper. However, vocal tics, always extremely resistant to pharmacological treatment, decreased significantly, along with the motor tics, when aripiprazol was introduced.

In the current model about the pathogenesis of TS which involve cortical-subcortical circuits, it is believed that the increase in the dopaminergic stimulation in the striatal region implies higher release of glutamate in the thalamic-cortical projections, leading to release of involuntary movements.^3-4

Aripiprazol has been described as a stabilizer of the dopamin/serotonin system. Its suggested mechanism of action is the partial agonism on D2 receptors, as it binds more to D2 G-protein bound receptors than to those which are not.² The affinity of the drug for D2 is 4- to 20 times lower than that of haloperidol, chlorpromazine or other typical antipsycotics.⁵ Besides, it shows a partial agonist activity on 5HT1A receptors and antagonism on 5HT2A receptors. Most neocortex 5HT1A receptors are situated in glutamatergic pyramidal neurons. These receptors have a inhibitory action, which would reduce the excitatory glutamatergic output. It is believed that part of the control of tics would stem from this control in the glutamatergic projection pathways.

Aripiprazol, therefore, with a profile of side-effects characterized by lower weight gain, lower sedation, absence of prolactine levels elevation and of widening of QT space of electrocardiogram compared to other antipsycotics, becomes an interesting option for TS cases which do not respond to conventional therapies. It has, however, a high cost and needs official support to allow the poorest layers of the population to benefit from its effects. Controlled studies comparing aripiprazol to the conventional treatments for TS are needed.

Refererences

1. Sandor P. Pharmacological management of tics in patients with TS. Journal of Psychossomatoc Research. 2003;55:41-8.

2. Burris KD, Molski TF, Xu C, et al. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther. 2002;302(1):381-9.

3. Alexander GE, De Long MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 1986;9:357-81.

4. Singer HS. Neurobiology of Tourette Syndrome. Neurol Clin.1997;15:357-79.

5. Lawer CP, Prioleau C, Lewis MM, et al. Intercations of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes. Neuropsychopharmacol. 1999;20(6):612-27.

Publication Dates

• Publication in this collection
  23 Feb 2005
• Date of issue
  Sept 2004