Review of: Sallee F et al,   J Child Adolesc Psychopharmacol 2017;27(9):771–781

Tourette’s disorder (TD) is a movement disorder emerging during childhood that causes persistent motor and vocal tics. TD is treated with a variety of medications, but often with an off-label designation. There are only three medications that are FDA approved for TD: haloperidol, pimozide, and most recently, in 2014, aripiprazole. But how impressive was the evidence for aripiprazole’s efficacy? The evidence that formed the basis of aripiprazole’s approval was just published, and we took a close look.

This study, a multicenter, randomized, double-blind trial conducted over an 8-week period with children and adolescents ages 7–17 with TD, evaluated the efficacy and safety of low-dose and high-dose aripiprazole for TD compared to placebo. After recruiting 133 patients across 76 sites in the United States, Canada, Hungary, and Italy, the primary outcome measured the change in the Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS). The patients were randomized in a 1:1:1 fashion to low-dose aripiprazole (patients < 50 kg received 5 mg/day and those ≥ 50 kg received 10 mg/day), high-dose aripiprazole (< 50 kg received 10 mg/day and ≥ 50 kg received 20 mg/day), or placebo. In addition to various scales to monitor for adverse effects, a key secondary outcome was the Clinical Global Impression-Tourette’s Syndrome (CGI-TS) improvement scale score.

The study showed a statistically significant improvement in the YGTSS-TTS in both the low-dose (26.7 point improvement, p = 0.002) and high-dose (32.8 point improvement, p < 0.0001) treatment groups compared to placebo at week 8. In addition, statistically significant differences in both treatment arms were seen at nearly each time point from weeks 1 to 8. The secondary outcome (CGI-TS improvement score) also demonstrated aripiprazole’s superiority, separating from placebo at each time point from weeks 1 to 8.

How about side effects? The study found that 65.9%, 75.6%, and 40.9% of patients in the low-dose, high-dose, or placebo groups, respectively, reported at least one adverse event—most commonly sedation, increased appetite, or fatigue. Due to adverse effects, usually fatigue, 8 patients (9%) in the treatment group discontinued the study, compared to only 1 patient in the placebo group. Seven of the dropouts were in the high-dose, low-weight group.

CCPR’s take
This fairly large clinical trial showed that aripiprazole is indeed more effective than placebo for treating TD. Higher doses (10–20 mg daily) were somewhat more effective than lower doses (5–10 mg daily), but at the cost of more side effects. As in many industry-funded clinical trials, the participants were less complicated (no history of psychotic disorders and no diagnosis of a primary mood disorder or other neurological disorders with abnormal movements) than many of the children we see in clinical practice, so you may or may not see as positive an effect in actual patients.