A total of 12 subjects were enrolled (mean age ± standard deviation [SD], 11.33 ± 2.35 years; age range 7–14; 11 males, 1 female). Two subjects were Hispanic, one was African-American, and the remaining subjects were Caucasian. All 12 subjects provided data over 6 weeks of the study and were used for analyses. Of the 12 subjects enrolled in the study, 4 (33.3%) had previously taken clonidine for TS treatment, 3 (25%) had prior risperidone or haloperidol treatment, and 3 (25%) had received other forms of psychotropic medication for non-tic symptoms. Six (50%) had no prior medication treatment for TS. No subject was withdrawn from an effective treatment.
In this study, all subjects (100%) had at least one co-morbid diagnosis at baseline visit (see ).Of the 12 subjects, 8 (66.7%) had two co-morbid diagnoses, 3 (25%) had three co-morbid diagnoses, and 3 (25%) had four or more comorbid diagnoses. Nine of the 12 subjects (75%) met criteria for at least one disruptive behavior disorder (ADHD, ODD, or CD). The most commonly occurring co-morbid diagnosis was ADHD (67.7%), followed by social phobia (33.3%).
Percentage of Tourette Syndrome Subjects by Co-Morbid Diagnoses
Primary outcome measure: Effectiveness of olanzapine of motor and vocal tic symptoms
Statistically significant pre–post treatment decreases were noted for all motor tic category variables with repeated measures analyses: number (f = 2.91, df = 6, p = 0.015), frequency (f = 3.69, df = 6, p = 0.003), intensity (f = 2.55, df = 6, p = 0.029), complexity (f = 2.41, df = 6, p = 0.037) interference (f = 2.71, df = 6, p = 0.021) and severity (f = 3.36, df = 6, p = 0.006). Repeated measures analyses of the vocal tic categories showed statistically significant changes from baseline across to week 6 ratings in interference (f = 2.53, df = 6, p = 0.03) and a trend toward significance in vocal tic severity scores (f = 1.963, df = 6, p = 0.085).
Total tic categories were calculated by summing motor and vocal tic scores. Significant drops in total tic frequency (f = 2.93, df = 6, p = 0.014), intensity (f = 2.29, df = 6, p = 0.047), interference (f = 3.36, df = 6, p = 0.006), impairment (f = 6.45, df = 7, p = 0.001), and total tic severity (f = 3.12, df = 6, p = 0.01) were observed. Effect sizes were calculated for each of the motor, vocal, and total tic variables. The effect sizes indicate a small-to-moderate effect size for all categories, the smallest at 0.19 for vocal tic complexity and the largest at 0.52 for global severity.
Secondary outcome measure 1: Effectiveness of olanzapine on associated symptoms of overactivity, aggression, and other disruptive behaviors
To assess the effectiveness of olanzapine on overactivity, aggression, and other disruptive behaviors, categories from the parent version of the SNAP IV Rating Scale were used. The SNAP IV Scale categories included: ADHD Inattention, ADHD Hyperactivity/Impulsivity, ODD, Inattention/Over-activity, Aggression/Defiance, and Conner's Index. General linear model repeated measures analyses identified statistically significant within-subject decreases for all parent SNAP Rating Scale categories: ADHD Inattention (f = 7.19, df = 4, p < 0.001), ADHD Hyperactivity/ Impulsivity (f = 10.69, df = 4, p < 0.001), ODD (f = 5.65, df = 4, p = 0.001), Inattention/Overactivity (f = 8.97, df = 4, p = 0.002), Aggression/Defiance (f = 4.17, df = 4, p = 0.009), and Conner's Index (f = 8.62, df = 4, p < 0.001).
Analysis of total OAS score indicated that no significant within subject differences existed for overall OAS score. When analyzing the number of episodes, as defined by the OAS Scale, statistically significant between-subject (f = 10.19, df = 1, p < 0.02) decreases existed.
Both child and parent reported anxiety scores were measured using the MASC. The four scales evaluated were the Physical Symptoms, Harm Avoidance, Social Anxiety, and Separation Anxiety/Panic. Repeated measure analyses of these scales showed a significantly lower score in child reported Physical Symptoms across treatment weeks (f = 2.69, df = 4, p< 0.05), however all other scores did not differ.
Secondary outcome measure 2: Short-term safety of olanzapine in children and adolescents
A repeated measures analysis of side effect data indicated that all 12 subjects receiving olanzapine experienced an increase in weight over the 6-week trial period (f = 27.32, df = 6, p < 0.001). The mean percent change from baseline to week 6 was 8.4 ± 4.4 (t = 6.55, p < 0.001). In addition, a paired t-test showed a significant increase between initial and final body mass index (BMI) measurements (t = –2.885, df = 5, p = 0.03). Other common side effects included drowsiness (see ), increased appetite, and sedation. From baseline to week 6, a significant increase was observed in heart rate (73 vs. 86, respectively, t = 3.16, p = 0.009). Systolic blood pressure showed an increase that was not significant (110 vs. 117, respectively, t = 2.07, p = 0.063). Diastolic pressure showed no change. Paired t-tests of pre- and week-6 nonfasting lab results showed several statistically significant changes from baseline (see ), but none was deemed clinically significant (all values within normal ranges). No significant changes in nonfasting glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), or triglycerides concentrations were observed.
Frequency of Reports of Drowsiness/Sedataion during 6-Week Exposure to Olanzapine
Lab Report Comparison between Initial and Final Visit
Symptom Measures at Baseline and Week 6 for 12 Subjects Treated with Olanzapine
Secondary outcome measure 3: Dosage effects on both tic and associated behavioral symptoms
Two of the 12 subjects (16.7%) decreased olanzapine dosage at some time between first and last visit, one for enuresis and the other for excessive sedation. Mean final daily dosage was 11.3 ± 5.6 mg/day (range 2.5–20 mg). Absolute daily dosage was not significantly correlated with pre-post treatment changes on any of the tic measures. A mixed-model regression using week, dosage, and week by dosage interaction indicated no significant effect on any motor, vocal, or total tic categories.