Emerging Treatment Strategies in Tourette Syndrome: What's in the Pipeline?
ABSTRACT 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.
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ABSTRACT: Three levels of investigation underlie all biologically based attempts at classification of behaviorally defined developmental and psychiatric disorders: Level A, pseudo-categorical classification of mostly dimensional descriptions of behaviors and their disorders included in the 2013 American Psychiatric Association's Fifth Edition of the Diagnostic and Statistical Manual (DSM-5); Level C, mostly categorical classification of genetic and environmental causes (etiologies) of Level A disorders; and Level B, the pathophysiologic-both categorical and dimensional-biologic mechanisms underlying Level A "diagnoses" which comprise hierarchically interacting molecular, cellular, and neural networks and major brain pathways orchestrated by Level C etiologies. Besides modest numbers of effective psychotropic medications and their derivatives, major advances in treatment have addressed the behavioral symptoms of Level A-defined developmental and psychiatric disorders. The National Institute of Mental Health proposes support for a new biologically based Research Domain Criteria (RDoC) classification; its goal is to apply to behaviorally defined Level A developmental and psychiatric disorders the biologically based Level C and Level B research strategies that have greatly accelerated treatment and prevention of medical disorders. It plans to supplement effective educational and behavioral symptom-based interventions with faster, more potent and specific biologic therapies and, hopefully, to discover how effective behavioral interventions alter brain function. This commentary raises the question of whether a hybrid nosology that maps biology onto behavior is attainable. At a minimum, such a nosologic effort requires greater in-depth and better informed dialog between investigators of behavior and biology than occurs typically, and more realistic communication of the implications of research results to the public.Journal of Autism and Developmental Disorders 05/2014; · 3.06 Impact Factor
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ABSTRACT: Tourette syndrome (TS) is a highly heritable yet heterogeneous childhood onset disorder. The cardinal movement disorder required for diagnosis is tics. As persons with tics or TS often have obsessive/compulsiveness, inattention, hyperactivity, impulsivity, anxiety, and anger outbursts, the presence of tics should prompt clinicians to look for these other conditions. While randomized controlled trials provide valid evidence of efficacy for symptoms in isolation, implications for treatment of complex patients meeting criteria for multiple diagnoses is not always clear. In this review, the authors critically review factors influencing decisions whether and how to treat medically tics as well as OCD and ADHD in the presence of tics.Journal of Obsessive-Compulsive and Related Disorders 04/2014; · 0.81 Impact Factor
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ABSTRACT: A large body of evidence using experimental animal models shows that the nicotinic cholinergic system is involved in the control of movement under physiological conditions. This work raised the question whether dysregulation of this system may contribute to motor dysfunction and whether drugs targeting nicotinic acetylcholine receptors (nAChRs) may be of therapeutic benefit in movement disorders. Accumulating preclinical studies now show that drugs acting at nAChRs improve drug-induced dyskinesias. The general nAChR agonist nicotine, as well as several nAChR agonists (varenicline, ABT-089 and ABT-894) reduce L-dopa-induced abnormal involuntary movements or dyskinesias up to 60% in parkinsonian nonhuman primates and rodents. These dyskinesias are potentially debilitating abnormal involuntary movements that arise as a complication of L-dopa therapy for Parkinson's disease. In addition, nicotine and varenicline decrease antipsychotic-induced abnormal involuntary movements in rodent models of tardive dyskinesia. Antipsychotic-induced dyskinesias frequently arise as a side effect of chronic drug treatment for schizophrenia, psychosis and other psychiatric disorders. Preclinical and clinical studies also show that the nAChR agonist varenicline improves balance and coordination in various ataxias. Lastly, nicotine has been reported to attenuate the dyskinetic symptoms of Tourette's disorder. Several nAChR subtypes appear to be involved in these beneficial effects of nicotine and nAChR drugs including α4β2*, α6β2* and α7 nAChRs (the asterisk indicates the possible presence of other subunits in the receptor). Overall, the above findings, coupled with nicotine's neuroprotective effects, suggest that nAChR drugs have potential for future drug development for movement disorders.Pharmacology [?] Therapeutics 05/2014; · 7.75 Impact Factor