Determining Clinically Meaningful Improvement in Children and Adolescents with Tourette Syndrome Receiving Pharmacotherapy.

Introduction: Accurate assessment of treatment outcomes in patients with Tourette syndrome (TS) is essential for evidence-based clinical care. This report determined the minimal clinically important difference (MCID) on the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (YGTSS-TTS) and YGTSS Impairment Scale (YGTSS-I), using the Clinical Global Impression of TS Severity (CGI-TS-S) and Improvement (CGI-TS-I) as anchors, in pediatric patients with TS receiving pharmacotherapy. Materials and Methods: Analyses used data from two clinical trials of ecopipam (a randomized controlled trial and its open-label extension). Receiver operating characteristic (ROC) analysis determined the percentage reduction in YGTSS scores that distinguished patients with improvement from those with no change or worsening on the CGI-TS-S and CGI-TS-I. Spearman's correlation, empirical cumulative distribution function, and probability distribution function analyses examined relationships between YGTSS-TTS and CGI-TS-S or CGI-TS-I. Results: Overall, 133 patients (75.2% male; mean [SD] age, 12.7 [2.8]) were included; 63.2% had improvement on the CGI-TS-S, and 78.2% showed improvement on the CGI-TS-I. Percentage reduction in YGTSS scores that distinguished improvement from no change or worsening on the CGI-TS-S and CGI-TS-I ranged from 18.6%-33.3% (area under the ROC curve range, 0.71-0.81). Improvement on the YGTSS-TTS was correlated with posttreatment CGI-TS-S (r = -0.65; p < 0.001) and CGI-TS-I (r = -0.61; p < 0.001) scores. The MCID for YGTSS-TTS was achieved by 67% and 62% of patients with improvement on the CGI-TS-S and CGI-TS-I, respectively. Conclusions: This analysis is the first to determine the MCID for YGTSS in a pediatric population with TS receiving pharmacotherapy. Whether using CGI-TS-S or CGI-TS-I as the anchor, a 25% reduction in YGTSS scores was a generally appropriate minimum threshold to define clinically meaningful improvement in this population. Findings offer an objective threshold for classifying clinically meaningful improvement in children and adolescents receiving pharmacotherapy for TS in clinical practice.