A Double-Blind Comparison of Risperidone and Pimozide in Patients with Tourette’s Syndrome and Neuropsychological Predictors of Treatment Response

Grant Type
Grant Year
Institution Location
Institution Organization Name
Marmara University Hospital Turkey
Investigators Name
Yazgan, M. Yanki, MD

Medication, in conjunction with psychosocial approaches, has been an important part of Tourette Syndrome (TS) treatment. The standard treatment with haloperidol is effective in most cases. However, extrapyramidal side effects (e.g., parkinsonian symptoms, akathisia, acute dystonia) and potential risk of tardive dyskinesia have led researchers to seek alternative medications. Clonidine (an alpha-2 adrenergic agonist) has been safely used as an alternative, but its effectiveness relative to standard treatment is limited. Pimozide has emerged as a neuroleptic alternative with a comparable efficacy to haloperidol, and a somewhat lower potential for extrapyramidal and sedating side effects. Risperidone is a new antipsychotic agent with different pharmacological properties and reportedly minimal extra-pyramidal and sedating side effects at low doses in the treatment of psychotic disorders. During my Fellowship at the Yale Child Study Center, risperidone was found to be effective for treatment of tics in an open label trial. With TSA’s support, our group in Istanbul, Turkey (which consists of child and adult psychiatrists and neurologists) will be conducting a randomized, double-blind, controlled, parallel groups study to compare the efficacy and short-term adverse effects of risperidone and, a standard medication for TS, pimozide. We are also interested in alterations of specific and simple neurobehavioral measures during the course of TS treatment, and the relationship of those alterations to clinical outcome, and patient characteristics. Few, if any, previous studies have shown changes in specific neurobehavioral measures in the treatment of TS. Moreover, no specific predictors of treatment response have been identified for TS patients. We previously put together a battery of simple neurobehavioral measures that significantly correlated with tic severity and the size of certain brain regions (the basal ganglia and the corpus callosum) both of which are potentially involved in TS pathophysiology. In this study, we will compare subjects’ performances on our battery over the course of their treatment with risperidone and pimozide. Comparing the efficacy of risperidone to standard treatment will expand the TS treatment repertoire. We will be particularly interested in side effect profiles of both medications in TS patients since possible side effects as well as effectiveness of medication are the two most important factors to weigh when selecting a medication. Determination of accompanying neurobehavioral changes and predictors of treatment response will allow us to identify important and specific clinical correlates of treatment responsiveness. In addition to its practical consequences for individuals, such a finding may guide identification of the pathophysiology of TS and may help generate hypotheses for future neuroimaging and neuropathology studies. The opportunity to carry out this research in Turkey will have a significant and positive impact on individuals with TS in this country. The increased attention to TS and careful characterization of participants by a multidisciplinary team will contribute to greater awareness about TS and encourage other individuals with TS to seek help. Data from this study will also provide the international TS research community with valuable information from a genetically somewhat different population M. Yanki Yazgan, M.D. Marmara University Hospital, Istanbul, Turkey Award $13,960 Tourette Association of America Inc. – Research Grant Award 1995