Aripiprazole Improves Symptoms of Aggression in Tourette Disorder

BOSTON—Aripiprazole may be an effective treatment option for tics and rage in children with Tourette disorder, according to preliminary data presented at the 54th Annual Meeting of the American Academy of Child and Adolescent Psychiatry. However, in the small patient population studied, the benefits of aripiprazole were accompanied by significant side effects, warranting a risk-benefit analysis with its use.

“The real problem is that it’s not just the tics, although those need to be addressed,” said session chair Barbara Coffey, MD, Associate Professor of Child and Adolescent Psychiatry at New York University’s Child Study Center in Manhattan. “It’s the other comorbid psychiatric disorders that are challenging for us, including behavioral problems, explosive outbursts, and other issues. Aggressive outbursts and rage attacks occur in a significant percentage of clinically referred patients with Tourette disorder, and are some of the most compelling and difficult symptoms to treat.”

EFFICACY VERSUS SIDE EFFECTS

Although haloperidol and pimozide are the only approved pharmacologic therapies for patients with Tourette disorder, these medications are often not first-line choices because of accompanying side effects such as risk for tardive dyskinesia, acute dystonic reactions, parkinsonism, cognitive dulling, galactorrhea, dysphoria, and sedation.

Cathy Budman, MD, and colleagues became interested in aripiprazole, an atypical antipsychotic with both dopaminergic and serotonergic effects, because of its reportedly fewer side effects compared with conventional antipsychotic medications. Dr. Budman said, “There is growing evidence that aripiprazole could be a useful treatment for tic suppression, and it has also been exploited for its antiaggressive properties in certain child psychiatry populations, such as children with conduct disorders, pervasive developmental disorder, and mood disorders.” Dr. Budman is an Associate Professor of Psychiatry at the New York University School of Medicine and Director of the Movement Disorders Program in Psychiatry at North Shore University Hospital in Manhasset, New York.

Dr. Budman and colleagues sought to explore the efficacy of aripiprazole for tics and explosive outbursts in a retrospective observational study of 37 children and adolescents ages 6 to 18 with Tourette disorder. The investigators started with doses of 1.25 to 2.5 mg/day in prepubertal children and 2.5 to 5 mg/day in adolescents, flexibly titrating the aripiprazole dose every five to seven days. Reductions in tic severity and explosive outbursts were assessed using the Clinical Global Impression (CGI) scale. Children with Tourette disorder and explosive outbursts experienced at least three episodes per week of severe impulsive aggression that was grossly out of proportion to any stressor or precipitant. Such episodes, often described as “rage attacks,” are characterized by the failure to resist severe aggressive impulses resulting in extreme verbal and/or physical destruction. Twenty-eight participants were taking concurrent psychotropic medications but were not permitted any change in medication one month before treatment and during the 12-week study. A high prevalence of comorbid psychiatric disorders was observed among subjects enrolled in this specialty clinic–based study, including obsessive-compulsive disorder (84%), ADHD (84%), bipolar affective disorder (19%), pervasive developmental disorder (16%), non-OCD anxiety disorders (5%), and major depressive disorder (3%).

THE BENEFITS AND RISKS OF ARIPIPRAZOLE THERAPY

The researchers found that at an average dose of 12 mg/day (range, 2.5 to 40 mg daily), aripiprazole significantly improved both tics and rage symptoms. Improvement was defined by a reduction in severity by 1 or more points on the CGI scale. Mean CGI scores at baseline were 4.35 and 5.0 for tics and rage and decreased to 2.73 and 2.53, respectively.

The investigators also found an unexpectedly high discontinuation rate; eight subjects (21%) stopped taking aripiprazole primarily due to extrapyramidal side effects such as akathisia and parkinsonism, as well as increased agitation. In addition, 13 of the 15 patients (87%) gained weight; the average weight gain in the three-month study period was 18 pounds. “Treatment with aripiprazole is believed to be less likely to result in weight gain than some of the other atypicals and conventional neuroleptics, but in our group of children with Tourette disorder, weight gain seemed to occur more frequently than expected,” Dr. Budman related. Other mild side effects included headache, dizziness, nausea, and sedation.

“The characterization of Tourette disorder is being defined as we speak,” said Dr. Coffey, who was a coinvestigator on the aripiprazole study. She referenced Georges Gilles de la Tourette, the French neurologist who described the first nine cases of the disorder in 1885. “We’ve certainly come a long way since then, but our treatments have their limitations, which is why we need to be thinking about novel directions.” Dr. Coffey is currently conducting an open-label safety and tolerability study of aripiprazole for tic suppression in children and adolescents with Tourette disorder.

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