A randomised, double-blind, placebo-controlled study of topiramate in the treatment of Tourette syndrome

Baylor College of Medicine, Department of Neurology, Houston, TX 77030, USA.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 6.81). 09/2009; 81(1):70-3. DOI: 10.1136/jnnp.2009.185348
Source: PubMed


To investigate the effects of topiramate on Tourette syndrome (TS).
Dopamine-receptor-blocking drugs have been traditionally used to control tics in patients with TS, but these neuroleptics are associated with potentially limiting side effects.
This is a randomised, double-blind, placebo-controlled, parallel group study. To be included in the study, subjects required a DSM-IV diagnosis of TS, were 7-65 years of age, had moderate to severe symptoms (Yale Global Tic Severity Scale (YGTSS) > or =19), were markedly impaired as determined by the Clinical Global Impression (CGI) scale severity score of > or =4 and were taking no more than one drug each for tics or TS comorbidities.
There were 29 patients (26 males), mean age 16.5 (SD 9.89) years, randomised, and 20 (69%) completed the double-blind phase of the study. The primary endpoint was Total Tic Score, which improved by 14.29 (10.47) points from baseline to visit 5 (day 70) with topiramate (mean dose 118 mg) compared with a 5.00 (9.88) point change in the placebo group (p = 0.0259). There were statistically significant improvements also in the other components of the YGTSS as well as improvements in various secondary measures, including the CGI and premonitory urge CGI. No differences were observed in the frequency of adverse events between the two treatment groups.
This double-blind, placebo-controlled trial provides evidence that topiramate may have utility in the treatment of moderately severe TS.

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Available from: Joseph Jankovic, Oct 08, 2014
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    • "Tel.: +44 121 3012317; Fax: +44 121 3012291; E-mail: havioural problems, such as attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) [4] [5]. It is estimated that GTS affects 1–8 per 1000 children [6] worldwide [7], in different degrees of severity [7], however due to misdiagnosis in reality prevalence may be even higher. "
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    ABSTRACT: Introduction: Gilles de la Tourette Syndrome (GTS) is a childhood-onset hyperkinetic movement disorder defined by the chronic presence of multiple motor tics and at least one vocal tic and often complicated by co-morbid behavioural problems. The pharmacological treatment of GTS focuses on the modulation of monoaminergic pathways within the cortico-striato-thalamo-cortical circuitry. This paper aims to evaluate the efficacy and safety profiles of pharmacological agents used in the treatment of tics in patients with GTS, in order to provide clinicians with an evidence-based rationale for the pharmacological treatment in GTS. Method: In order to ascertain the best level of evidence, we conducted a systematic literature review to identify double-blind randomised controlled trials of medications in GTS populations. Results: We identified a large number of pharmacological agents as potentially effective in improving tic symptoms. The alpha-2 agonist Clonidine is amongst the agents with the most favourable efficacy-versus-adverse events ratio, especially in patients with co-morbid attention-deficit hyperactivity disorder, although effect sizes vary evidence-based studies. Discussion: Our results are in line with the findings of uncontrolled open-label studies. However, most trials have low statistical power due to the small sample sizes, and newer agents, such as Aripiprazole, have not been formally tested in double-blind randomised controlled trials. Further research should focus on better outcome measures, including Quality of Life instruments.
    Full-text · Article · May 2012 · Behavioural neurology
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    • "A naturalistic follow-up study from 2004 including 41 patients indicated that treatment with fluphenazine for at least one year was safe and effective.27 A retrospective review from 2009 also showed fluphenazine to be an effective and well-tolerated therapy.28 The main data were collected in a few older studies including placebo-controlled, double-blind trials between 1982 and 1985 which revealed that fluphenazine is effective in controlling tics, while having fewer side effects than haloperidol (small, open-label studies).29–31 "
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    ABSTRACT: Tourette syndrome (TS) is a neuropsychiatric disorder with typical onset in childhood and characterized by chronic occurrence of motor and vocal tics. The disorder can lead to serious impairments of both quality of life and psychosocial functioning, particularly for those individuals displaying complex tics. In such patients, drug treatment is recommended. The pathophysiology of TS is thought to involve a dysfunction of basal ganglia-related circuits and hyperactive dopaminergic innervations. Congruently, dopamine receptor antagonism of neuroleptics appears to be the most efficacious approach for pharmacological intervention. To assess the efficacy of the different neuroleptics available, a systematic, keyword-related search in PubMed (National Library of Medicine, Washington, DC) was undertaken. Much information on the use of antipsychotics in the treatment of TS is based on older data. Our objective was to give an update and therefore we focused on papers published in the last decade (between 2001 and 2011). Accordingly, the present review aims to summarize the current and evidence-based knowledge on the risk-benefit ratio of both first and second generation neuroleptics in TS.
    Preview · Article · Mar 2012 · Neuropsychiatric Disease and Treatment
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    • "Newer anticonvulsants such as topiramate and lamotrigine have not been fully investigated. Preliminary studies (Nelson et al. 2007; Jankovic et al. 2010) conducted in children with TD and tics show that topiramate may reduce tic severity by 50% in add-on therapy patients and by 51% in monotherapy patients. Lamotrigine is not indicated for children with tics or TD. "
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    ABSTRACT: The aim of this study was to review the efficacy of various treatments for Tourette's disorder (TD) and tics. This study is a historical review of the treatment modalities prior to the advent of neuroleptics. A review of double-blind and placebo-controlled clinical trials and open studies on the use of neuroleptics and selected reports was also carried out. The literature review reveals that the treatment of TD and tics has evolved from an early history of marginally effective approaches to the advent of neuroleptics, which started a new era in TD and tic treatment, with a significantly broader range of effectiveness. Although progress has been made, the literature review nevertheless reveals a great deal of confusion as related to the clinical heterogeneity of TD and tics, differences in populations, medication-dose combinations, and outcomes. However, a role for a limited number of pharmacologic agents, combined with psychosocial approaches, has been identified. There is a need for studies in larger, diagnostically homogenous samples and for the use of more sophisticated methodology, to identify intelligible models that would allow the development of more effective treatment approaches.
    Preview · Article · Aug 2010 · Journal of child and adolescent psychopharmacology
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