N-Acetylcysteine in the Treatment of Pediatric Tourette Syndrome: Randomized, Double-Blind, Placebo-Controlled Add-On Trial

Abstract

Background: Current pharmacological treatments for Tourette Syndrome (TS), such as antipsychotic agents and α-2 agonists, are moderately effective in the treatment of tics, but have substantial side effects that limit their use. N-acetylcysteine (NAC) modulates glutamatergic systems, and has been used safely as an antioxidant agent with minimal side effects for decades. NAC has been increasingly studied for the treatment of other obsessive-compulsive spectrum disorders. We aim to examine the efficacy of NAC for the treatment of pediatric TS in a double-blind, placebo-controlled, add-on study.

Methods: Thirty-one children and adolescents 8-17 years of age with TS were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of tics as measured by the Yale Global Tic Severity Scale (YGTSS), Total tic score. Secondary measures assessed comorbid obsessive-compulsive disorder (OCD), depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD). Linear mixed models in SAS were used to examine differences between NAC and placebo.

Results: Of 31 randomized subjects, 14 were assigned to placebo (two females; 11.5 + 2.8 years) and 17 to active NAC (five females; 12.4 + 1.4 years) treatment. No significant difference between NAC and placebo was found in reducing tic severity or any secondary outcomes.

Conclusions: We found no evidence for efficacy of NAC in treating tic symptoms. Our findings stand in contrast to studies suggesting benefits of NAC in the treatment of other obsessive-compulsive spectrum disorders in adults, including OCD and trichotillomania, but are similar to a recent placebo-controlled trial of pediatric trichotillomania that found no benefit of NAC.

Conflict of interest statement

Dr. Leckman receives royalties from John Wiley & Sons, McGraw Hill, and Oxford University. He also serves on the scientific advisory boards of National Organization for Rare Disorders (NORD) and the Brain and Behavior Research Foundation (formerly NARSAD). Other authors have no conflcits of interest to declare.

Figures

FIG. 1.

Selection of studies and search strategy.

FIG. 2.

Effects of N-acetylcysteine (NAC) and placebo on tic severity (Yale Global Tic Severity Scale [YGTSS]). There was no significant effect of NAC on tic severity over time in comparison with placebo.

FIG. 3.

Effects of N-acetylcysteine (NAC) and placebo on premonitory urge (Premonitory Urge Tic Scale [PUTS]). There was no significant effect of NAC on premonitory urge ratings over time in comparison with placebo.