To determine whether pergolide, a mixed D1/D2/D3 dopamine agonist, is efficacious and safe in the treatment of children with chronic tic disorders and Tourette syndrome.
Neuroleptics, which block dopamine transmission, are currently used to treat children with severe tics, but major side effects and limited efficacy reduce clinical utility. Prior open-label and crossover studies of pergolide suggest potential benefit.
The authors enrolled 57 children and adolescents, ages 7 to 17 years, randomizing them in a 2:1 ratio to either pergolide (0.15 to 0.45 mg per day) or placebo. Tic symptoms had to be >30 on the Yale Global Tic Severity Scale (YGTSS). The primary outcome measure was change in tic severity assessed by YGTSS.
Compared to placebo treatment, pergolide treatment was associated with lower tic severity scores (treatment effect 8.8, pergolide vs placebo; 95% CI 0.1 to 17.6; p = 0.05) and attention-deficit hyperactivity disorder symptoms scores (treatment effect 3.8; 95% CI 0.7 to 6.8; p = 0.02). No patient had a serious adverse event and pergolide was well tolerated.
In this randomized, placebo-controlled trial, pergolide appeared to be an efficacious and safe medication for tic reduction in children, and may also improve attention-deficit hyperactivity disorder symptoms.
"Results for the anticonvulsant levetiracetam have been mixed (Awaad, Michon, & Minarik, 2005; Hedderick, Morris, & Singer, 2009; Smith-Hicks, Bridges, Paynter, & Singer, 2007). The use of dopamine agonists pergolide (no longer marketed) (Gilbert et al., 2003) and ropinirole (Anca, Giladi, & Korczyn, 2004) for tics initially appeared promising, but a controlled trial of pramipexole, another dopamine agonist, showed no benefit (Kurlan et al., 2012). The third tier medications include the anti-dopaminergic drugs, either dopamine receptor blocking agents, also known as neuroleptics or antipsychotics, or dopamine depletors, such as tetrabenazine. "
[Show abstract][Hide abstract] 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; 3(4). DOI:10.1016/j.jocrd.2014.04.006 · 1.18 Impact Factor
"Although several studies have confirmed the supersensitivity of the dopamine system in tic disorders, these studies did not consider the anti-dopaminergic drug effects [55–57], and several neuroimaging studies assessing influences of drugs on the dopamine system have yielded conflicting results [58–60]. Significantly, pergolide, a typical dopamine agonist, reduced tic symptoms in two previous randomized, controlled clinical studies [61, 62]. Thus, an imbalance in dopamine systems may be a pivotal cause of tic disorders. "
[Show abstract][Hide abstract] ABSTRACT: Due to its unique pharmacodynamic properties of dopamine partial agonist activity, and its association with few and mild side effects, aripiprazole is a candidate atypical antipsychotic for patients with tic disorders. This open-label study compared the efficacy and tolerability of aripiprazole with haloperidol, a typical antipsychotic widely used to treat patients with tic disorders. Forty-eight children and adolescents with tic disorders were recruited from the outpatient clinic at South Korea and treated with aripiprazole (initial dose, 5.0 mg/d; maximum dose 20 mg/d) or haloperidol (initial dose, 0.75 mg/d; maximum dose, 4.5 mg/d) for 8 weeks. Treatment efficacy was measured using the yale global tic severity scale (YGTSS), and tolerability was measured using the extrapyramidal symptom rating scale (ESRS) and an adverse effects checklist. Total tic scores as measured by the YGTSS decreased over time in both groups (p < 0.001) without any significant differences between groups. ESRS scores were significantly higher in the haloperidol group during the 4 weeks after commencement of medication (p < 0.05). These results indicate that aripiprazole may be a promising drug in the treatment of children and adolescents with tic disorders. Further controlled studies are needed to determine the efficacy and tolerability of aripiprazole in these patients.
"Pro-dopaminergic medications to treat TD may first have been suggested 30 years ago (Feinberg and Carroll 1979). Subsequently, a number of small open-label and randomized, controlled trials have suggested that dopamine agonists may have a modest effect in reducing tic scores (Lipinski et al. 1997; Black and Mink 2000; Gilbert et al. 2003; Anca et al. 2004) similar to benefit in restless leg syndrome (Earley et al. 1998). "
[Show abstract][Hide abstract] ABSTRACT: Tics are intermittent, repetitive, patterned but usually nonrhythmic motor movements or sounds performed in response to urges or involuntarily. They are the cardinal symptom required for a DSM-IV-TR diagnosis of Tourette's disorder (TD). Many children with TD present with mild tics that cause no significant impairment. However, when tics cause pain or interference, medical treatment is reasonable. This article reviews current evidence for treatment of tics in TD with medications as well as deep brain stimulation and transcranial magnetic stimulation. It concludes with some context for understanding this literature, relevant to treatment decisions and future treatment research in TD.
Journal of child and adolescent psychopharmacology 08/2010; 20(4):263-76. DOI:10.1089/cap.2010.0015 · 2.93 Impact Factor
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