Monday, February 10, 2020

Topiramate and Tourette syndrome

Jankovic J. Treatment of tics associated with Tourette syndrome. J Neural
Transm (Vienna). 2020 Jan 18. doi: 10.1007/s00702-019-02105-w. [Epub ahead of

Motor and phonic tics associated with Tourette syndrome (TS) can range in severity from barely perceptible to disabling and most patients have a variety of behavioral co-morbidities, particularly, attention deficit disorder and obsessive compulsive disorder. Therefore, therapy must be tailored to the individual needs of the patients. In addition to behavioral therapy, oral medications such as alpha agonists, dopamine depletors, anti-psychotics, and topiramate are used to control the involuntary movements and noises. Botulinum toxin injections are particularly effective in patients with troublesome focal motor and phonic tics, including coprolalia. Deep brain stimulation may be considered for patients with "malignant" TS, that is, refractory to medical therapy. When appropriate therapy is selected and implemented, most patients with TS can achieve their full potential and lead essentially normal life.print] 

Quezada J, Coffman KA. Current Approaches and New Developments in the Pharmacological Management of Tourette Syndrome. CNS Drugs. 2018 Jan;32(1):33-45.

Tourette syndrome (TS) is a neurodevelopmental disorder of unknown etiology characterized by spontaneous, involuntary movements and vocalizations called tics. Once thought to be rare, TS affects 0.3-1% of the population. Tics can cause physical discomfort, emotional distress, social difficulties, and can interfere with education and desired activities. The pharmacologic treatment of TS is particularly challenging, as currently the genetics, neurophysiology, and neuropathology of this disorder are still largely unknown. However, clinical experience gained from treating TS has helped us better understand its pathogenesis and, as a result, derive treatment options. The strongest data exist for the antipsychotic agents, both typical and atypical, although their use is often limited in children and adolescents due to their side-effect profiles. There are agents in a variety of other pharmacologic categories that have evidence for the treatment of TS and whose side-effect profiles are more tolerable than the antipsychotics; these include clonidine, guanfacine, baclofen, topiramate, botulinum toxin A, tetrabenazine, and deutetrabenazine. A number of new agents are being developed and tested as potential treatments for TS. These include valbenazine, delta-9-tetrahydrocannabidiol, and ecopipam. Additionally, there are agents with insufficient data for efficacy, as well as agents that have been shown to be ineffective. Those without sufficient data for efficacy include clonazepam, ningdong granule, 5-ling granule, omega-3 fatty acids, and n-acetylcysteine. The agents that have been shown to be ineffective include pramipexole and metoclopramide. We will review all of the established pharmacologic treatments, and discuss those presently in development.

Termine C, Selvini C, Rossi G, Balottin U. Emerging treatment strategies in Tourette syndrome: what's in the pipeline? Int Rev Neurobiol. 2013;112:445-80.

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor/phonic tics and a wide spectrum of behavioral problems (e.g., complex tic-like symptoms, attention deficit hyperactivity disorder, and obsessive-compulsive disorder). TS can be a challenging condition even for the specialists, because of the complexity of the clinical picture and the potential adverse effects of the most commonly prescribed medications. Expert opinions and consensus guidelines on the assessment and treatment of tic disorders have recently been published in Europe and Canada. All pharmacological treatment options are mere symptomatic treatments that alleviate, but do not cure, the tics. We still lack evidence of their effects on the natural long-term course and on the prognosis of TS and how these treatments may influence the natural course of brain development. The most commonly prescribed drugs are dopamine antagonists, such as typical (e.g., haloperidol, pimozide) and atypical neuroleptics (e.g., risperidone, aripiprazole), and α-2-adrenoreceptor agonists (e.g., clonidine). However, several studies have investigated the efficacy and tolerability of alternative pharmacological agents that may be efficacious, including the newest atypical antipsychotic agents (e.g., paliperidone, sertindole), tetrabenazine, drugs that modulate acetylcholine (e.g., nicotine) and GABA (e.g., baclofen, levetiracetam), tetrahydrocannabinol, botulinum toxin injections, anticonvulsant drugs (e.g., topiramate, carbamazepine), naloxone, lithium, norepinephrine, steroid 5α reductase, and other neuroactive agents (buspirone, metoclopramide, phytostigmine, and spiradoline mesylate). As regards nonpharmacological interventions, some of the more recent treatments that have been studied include electroconvulsive therapy and repetitive transcranial magnetic stimulation. This review focuses primarily on the efficacy and safety of these emerging treatment strategies in TS.

Yang CS, Zhang LL, Zeng LN, Huang L, Liu YT. Topiramate for Tourette's syndrome in children: a meta-analysis. Pediatr Neurol. 2013 Nov;49(5):344-50.


To assess the efficacy and safety of topiramate for children with Tourette syndrome.

Randomized controlled trials evaluating topiramate for children with Tourette syndrome were identified from the Cochrane library, PubMed, Cochrane Central, Embase, CBM, CNKI, VIP, WANG FANG database, and relevant reference lists. Two reviewers independently selected trials, assessed trial quality, and extracted the data. Disagreement was resolved by discussion. Quality assessment referred to the Cochrane Handbook for Systematic Reviews of Interventions (version 5.0.1.).

Fourteen trials involving 1003 patients were included, of which 720 cases were male (71.8%). Ages were 2 to 17 years old. The general quality of included randomized controlled trials was poor. All trials were positive drug-controlled (12 randomized controlled trials used haloperidol as control, 2 used tiapride). The follow-up period was from 20 days to 12 months. Meta-analysis of 3 trials (n = 207), in which tics symptoms control was assessed by Yale Global Tic Severity Scale, suggested that there was significant difference in the mean change of Yale Global Tic Severity Scale score during the treatment period (mean difference = -7.74, 95% CI [-10.49, -4.99], I(2) = 0) between topiramate and control groups. Meta-analysis of 9 trials (n = 668) evaluating tics symptoms control ≥ 50% suggested that there was no significant difference in reduction of tics between topiramate and control group during the treatment period (relative ratio = 1.36, 95% CI [0.90, 2.06], I(2) = 0). Adverse events were reported in 13 trials. Drowsiness (3.3-16%), loss of appetite (4-16.7%), cognitive dysfunction (7.89-12.5%), and weight loss (6-10.5%) were common adverse events.

The current evidence is promising but not yet sufficient to support the routine use of topiramate for Tourette syndrome in children due to low quality of the study designs. It deserves to confirm in further high-quality, placebo-controlled trials.

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