Original Article Open Label Aripiprazole in the Treatment of Youth with Tic Disorders Tanya K. Murphy, M.D., 1 P. Jane Mutch, Ph.D., 1 Jeannette M. Reid, B.S., 1 Paula J. Edge, B.S., 2 Eric A. Storch, Ph.D., 1 Michael Bengtson, M.D., 2 and Mark Yang, Ph.D. 3 Abstract Background: Primarily safe and efficacious treatments for chronic tic disorders are needed. Also needed are such treatments that target co-morbid conditions. Aripiprazole, a dopaminergic=serotonergic agent with partial agonist properties at the D2 dopamine receptor and 5-hydrdoxytryptamine 1A (5-HT 1A ) receptor and antagonist properties at the 5-HT 2A receptor, holds promise in both regards. Objective: This was an open-label, flexible-dose study to evaluate the safety of aripiprazole in children and ado- lescents with a primary diagnosis of a chronic tic disorder with=without co-morbid disorder(s). Method: Sixteen children (15 males) aged 8–17 years participated in the 6-week trial. Ratings for tic, obsessive compulsive disorder (OCD), attention-deficit=hyperactivity disorder (ADHD), and side effects were administered weekly. Baseline and exit laboratory measures, electrocardiograms (ECGs), weight, and height were obtained. Results: The average daily aripiprazole dose was 3.3 mg (range 1.25–7.5 mg). Significant pre-and posttreatment differences were ascertained for the Yale Global Tic Severity Scale motor ( p  0.0001), phonic ( p  0.0001), and total tic ( p  0.0001) scores. Results of other rating scales suggested significant improvements in co-morbid disorders as well, including OCD, ADHD, and depressive disorders. Although aripiprazole was well tolerated, increases in weight were found. Conclusion: In this preliminary open-label trial, aripiprazole was a well-tolerated treatment for tics and co-morbid OCD and ADHD symptoms. Improvements in co-morbid conditions may be secondary to tic reduction or to specific to aripiprazole therapy; however, further study is warranted. Introduction T ics are sudden, rapid, recurrent, nonrhythmic motor movements or vocalizations that can be transient or chronic. Transient tics affect from 6–20% of school-aged chil- dren, with chronic tics and Tourette’s syndrome (TS) affecting between 0.5% and 1% of children (Robertson 2003; Swain et al. 2007). TS is characterized by both multiple motor and one or more vocal tics occurring nearly every day for more than 1 year. Although some cases will remit, TS often persists into adulthood and may negatively influence the individuals’ ability to develop and maintain healthy interpersonal and social relationships, autonomy, and academic success (Chang et al. 2004; Storch et al. 2007). Co-morbid psychopathology is common among TS patients and may include attention- deficit=hyperactivity disorder (ADHD), disruptive behavior disorders, obsessive compulsive disorder (OCD), and de- pressive disorders (Robertson et al. 2002). Often these co- morbid disorders contribute largely to functional impairment; for example, children and adolescents with TS who are also affected by ADHD may experience increased academic, social, and family difficulties, whereas those who have co- morbid OCD or depressive disorders may experience in- creased emotional and adaptive impairment (Swain et al. 2007). The decision to treat tic disorders is dependent upon sev- eral variables, including severity of the tics, co-morbid psychiatric disorders, and functional impairment. Non- pharmacologic treatments such as behavioral therapy show mixed results. Habit reversal training has worked well to im- prove tics with long-term effects (Wilhelm et al. 2003; Deck- ersbach et al. 2006); however, other behavioral techniques, such as biofeedback and awareness training, have not been studied adequately. Furthermore, while relaxation training was found to improve tics (Bergin et al. 1998), it only did so for the short-term. Furthermore, pharmacologic treatment is 1 Department of Pediatrics & Psychiatry, University of South Florida, St. Petersburg, Florida. 2 Department of Psychiatry and 3 Department of Statisticsm, University of Florida, Gainesville, Florida. The statistician for this study was Mark Yang, Ph.D. This investigator-initiated study was supported by a grant from Bristol-Myers Squibb. JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 19, Number 4, 2009 ª Mary Ann Liebert, Inc. Pp. 441–447 DOI: 10.1089=cap.2008.0149 441