Systematic Review: Pharmacological Treatment of Tic Disorders - Efficacy of Antipsychotic and Alpha-2 Adrenergic Agonist Agents.
Yale Child Study Center, Yale University School of Medicine, New Haven, CT. Neuroscience & Biobehavioral Reviews
(Impact Factor: 8.8).
10/2012; 37(6). DOI: 10.1016/j.neubiorev.2012.09.008
We conducted a meta-analysis of randomized, placebo-controlled trials to determine the efficacy of antipsychotic and alpha-2 agonists in the treatment of chronic tic disorders and examine moderators of treatment effect. Meta-analysis demonstrated a significant benefit of antipsychotics compared to placebo (standardized mean difference (SMD)=0.58 (95% confidence interval (CI): 0.36-0.80). Stratified subgroup analysis found no significant difference in the efficacy of the 4 antipsychotic agents tested (risperidone, pimozide, haloperidol and ziprasidone). Meta-analysis also demonstrated a benefit of alpha-2 agonists compared to placebo (SMD=0.31 (95% confidence interval CI: 0.15-0.48). Stratified subgroup analysis and meta-regression demonstrated a significant moderating effect of co-occurring ADHD. Trials which enrolled subjects with tics and ADHD demonstrated a medium-to-large effect (SMD=0.68 (95%CI: 0.36-1.01) whereas trials that excluded subjects with ADHD demonstrated a small, non-significant benefit (SMD=0.15 (95%CI: -0.06-0.36). Our findings demonstrated significant benefit of both antipsychotics and alpha-2 agonists in treating tics but suggest alpha-2 agonists may have minimal benefit in tic patients without ADHD.
Available from: Joshua M. Nadeau
- "Although efficacious, these medications are frequently accompanied by side effects that may limit tolerability and acceptability (Scahill et al., 2006a). Similarly, a meta-analysis of RCTs of alpha-2 agonists medications (e.g., guanfacine, clonidine) demonstrated their efficacy in reducing tic symptom severity, albeit with modest results (Weisman et al., 2012). Behavior therapy (e.g., habit reversal training, comprehensive behavioral intervention for tics) has also demonstrated efficacy in reducing tic symptom severity in RCTs for youth and adults (Piacentini et al., 2010; Himle et al., 2012; Wilhelm et al., 2012), with a meta-analysis of behavior therapy RCTs Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/psychres "
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ABSTRACT: Pharmacological and behavioral interventions have focused on reducing tic severity to alleviate tic-related impairment for youth with chronic tic disorders (CTDs), with no existing intervention focused on the adverse psychosocial consequences of tics. This study examined the preliminary efficacy of a modularized cognitive behavioral intervention ("Living with Tics", LWT) in reducing tic-related impairment and improving quality of life relative to a waitlist control of equal duration. Twenty-four youth (ages 7-17 years) with Tourette Disorder or Chronic Motor Tic Disorder and psychosocial impairment participated. A treatment-blind evaluator conducted all pre- and post-treatment clinician-rated measures. Youth were randomly assigned to receive the LWT intervention (n=12) or a 10-week waitlist (n=12). The LWT intervention consisted of up to 10 weekly sessions targeted at reducing tic-related impairment and developing skills to manage psychosocial consequences of tics. Youth in the LWT condition experienced significantly reduced clinician-rated tic-impairment, and improved child-rated quality of life. Ten youth (83%) in the LWT group were classified as treatment responders compared to four youth in the waitlist condition (33%). Treatment gains were maintained at one-month follow-up. Findings provide preliminary data that the LWT intervention reduces tic-related impairment and improves quality of life for youth with CTDs.
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Available from: Bénédicte Ballanger
- "Finally, it is worth mentioning that clonidine is effective in reducing impulsivity in other pathological conditions. This is especially the case for attention-deficit/hyperactivity disorder , Tourette's syndrome , and tic disorders  . "
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Slowness in movement initiation (akinesia) is a cardinal feature of Parkinson’s disease (PD), which is still poorly understood. Notably, akinesia is restored by subthalamic nucleus deep brain stimulation (STN-DBS) but not fully reversed by current dopaminergic treatments. It was recently suggested that this disorder is of executive nature (related to inhibitory control of response) and of non-dopaminergic origin (possibly noradrenergic).
To test the double hypothesis that: 1) the ability to control movement initiation is modified by noradrenergic neurotransmission modulation, and 2) this effect is mediated by the regulation of STN activity.
Sixteen STN-DBS PD patients were enrolled in a placebo-controlled study investigating the effects of noradrenergic attenuation by clonidine (∝2-adrenergic receptor agonist). Movement initiation latency was assessed by means of a cue-target reaction time task. Patients, who remained on their chronic dopaminergic medication, were tested on four sessions: two with placebo (ON- or OFF-DBS), and two with a 150 μg oral dose of clonidine (ON- or OFF-DBS).
In the OFF stimulation condition, patients were locked into a mode of control maintaining inappropriate response inhibition. This dysfunctional executive setting was overcome by STN-DBS. Clonidine, however, was found to impair specifically the ability to release inhibitory control in the ON-DBS state.
Overall our results suggest an important implication of the noradrenergic system in the pathophysiology of akinesia in PD. Reducing the noradrenergic “tonus” may even block the positive action of STN-DBS on akinesia, suggesting, at least by part, a noradrenergic-dependent STN-DBS efficiency.
Available from: Veit Roessner
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ABSTRACT: The present review gives an overview of current pharmacological treatment options of tic disorders and Tourette Syndrome (TS). After a short summary on phenomenology, clinical course and comorbid conditions we review indications for pharmacological treatment in detail. Unfortunately, standardized and large enough drug trials in TS patients fulfilling evidence based medicine standards are still scarce. Treatment decisions are often guided by individual needs and personal experience of treating clinicians. The present recommendations for pharmacological tic treatment are therefore based on both scientific evidence and expert opinion. As first-line treatment of tics risperidone (best evidence level for atypical antipsychotics) or tiapride (largest clinical experience in Europe and low rate of adverse reactions) are recommended. Aripiprazole (still limited but promising data with low risk for adverse reactions) and pimozide (best evidence of the typical antipsychotics) are agents of second choice. In TS patients with comorbid attention deficit hyperactivity disorder (ADHD) atomoxetine, stimulants or clonidine should be considered, or, if tics are severe, a combination of stimulants and risperidone. When mild to moderate tics are associated with obsessive-compulsive symptoms, depression or anxiety sulpiride monotherapy can be helpful. In more severe cases the combination of risperidone and a selective serotonin reuptake inhibitor should be given. In summary, further studies, particularly randomized, double-blind, placebo-controlled trials including larger and/or more homogenous patient groups over longer periods are urgently needed to enhance the scientific basis for drug treatment in tic disorders. This article is part of a Special Issue entitled 'Neurodevelopment Disorder'.
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