This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This is an investigator-initiated, pharmaceutically-sponsored open trial of Abilify, a novel atypical neuroleptic, for the treatment of motor and vocal tics in Tourette's disorder (TD). TD is now known to be substantially more common than previously believed, although impairing tics are still relatively uncommon. For such subjects, there are few desirable pharmacological options, and no readily available non-medical treatments. FDA approved treatments consist of haloperidol and pimozide, both of which have undesirable adverse effects, which results in most patients discontinuing treatment despite efficacy in tic reduction. Newer treatments have consisted mostly of atypical neuroleptics which are believed to have lower risks of tardive dyskinesia, but neuroleptics such as risperidone or olanzapine have been associated with profound weight gain and glucose intolerance. Aripiprazole (Abilify) is reported to be weight-neutral; it also has partial agonist/antagonist activity at the D2 receptor. A well-tolerated medication that has efficacy against tics would represent an important advance. This is an open trial to provide preliminary data. It is an 8-week trial with weekly visits. Participants will be 7 to 18 years old (inclusive) with DSM-IV TD or chronic motor tic disorder, who have failed an adequate trial of alternative medications, with tics that are causing significant distress or impairment. The primary hypothesis is that aripiprazole will reduce tics and tic-related impairment and tic severity; secondary hypotheses are that obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) symptoms, which are frequently associated, will also be reduced through 5-HT1a partial agonism, and D2 stabilization, respectively. Participants will undergo nearly weekly follow-up, doses will be minimal at initiation and titrated as needed to weight-related maxima of up to 10 mg/day for those weighing > 70 kg.
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