Relative efficacy of haloperidol and pimozide in children and adolescents with Tourette's disorder. Risperidone versus pimozide in Tourette's disorder: a comparative double-blind parallel-group study. Tic reduction with risperidone versus pimozide in a randomized, double-blind, crossover trial. A comparison of pimozide and haloperidol in the treatment of Gilles de la Tourette's syndrome. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. Prophylactic effects of neuroleptics in symptom-free schizophrenics: roles of dopaminergic and noradrenergic blockers.
The authors evaluated the relative efficacy and safety of pimozide and haloperidol in the treatment of Gilles de la Tourette's syndrome in children and adolescents.
                A double-blind, 24-week, placebo-controlled double crossover study of equivalent dose formulations of haloperidol and pimozide was conducted with 22 subjects, aged 7-16 years, with Tourette's disorder who were randomly assigned to first one active drug treatment and then the other. Biweekly assessment and flexible dose titration mimicked clinical practice. The primary outcome variable was total score on the Tourette Syndrome Global Scale. Final outcome was determined after 6 weeks of each treatment (placebo, pimozide, haloperidol), with a 2-week placebo baseline period and intervening 2-week placebo washout periods between treatments.
                Pimozide proved significantly different from placebo in affecting the primary outcome variable, whereas haloperidol failed to have a significant effect. Haloperidol exhibited a threefold higher frequency of serious side effects and significantly greater extrapyramidal symptoms relative to pimozide. Haloperidol-associated treatment-limiting adverse events were experienced by 41% of the patients. The therapeutic doses of pimozide and haloperidol were equivalent (mean = 3.4 mg/day, SD = 1.6, and mean = 3.5 mg/day, SD = 2.2, respectively).
                At equivalent doses, pimozide is superior to haloperidol for controlling symptoms of Tourette's disorder in children and adolescents. The treatment of Tourette's disorder with classical neuroleptics is limited by their side effects. Risperidone is a new efficacious antipsychotic with a low propensity for extrapyramidal side effects. To establish risperidone's therapeutic potential in Tourette's disorder, we studied the safety and efficacy of risperidone in comparison with pimozide in patients with Tourette's disorder diagnosed according to DSM-III-R.
                In a 12-week, multicenter, double-blind, parallel-group study, 26 patients were treated with risperidone (mean daily dose = 3.8 mg), and 24 patients were treated with pimozide (mean daily dose = 2.9 mg).
                There was significant improvement of tics with respect to the Tourette's Symptom Severity Scale (TSSS) for both groups. Forty-one patients completed the study. At endpoint, 54% (14/26) of the risperidone patients and 38% (9/24) of the pimozide patients had only very mild or no symptoms on the global severity rating of the TSSS. Both treatment groups had improved significantly at endpoint in regard to Global Assessment of Functioning and Clinical Global Impressions scale outcomes. Symptoms of anxiety and depressive mood improved significantly from baseline in both groups. Obsessive-compulsive behavior improvement reached significance only in the risperidone group. Although the severity of extrapyramidal side effects was low in both groups, fewer patients in the risperidone group reported extrapyramidal side effects (N = 4) compared with the pimozide group (N = 8). Depression, fatigue, and somnolence were reported as the most prominent side effects in both treatment groups.
                Both drugs were efficacious and well tolerated in patients with Tourette's disorder. Risperidone may become the first-line drug in the treatment of Tourette's disorder owing to a more favorable efficacy and tolerability profile. To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders.
                This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic motor tic disorder were randomized to 4 weeks of treatment with pimozide or risperidone, followed by the alternate treatment after a 2-week placebo washout. The primary efficacy outcome measure was change in tic severity assessed by the Yale Global Tic Severity Scale (YGTSS). ECG results, weight gain, and side effects were also compared.
                Compared to pimozide treatment, risperidone treatment was associated with significantly lower tic severity scores (YGTSS: baseline 43.3 +/- 17.5, pimozide 34.2 +/- 14.2, risperidone 25.2 +/- 13.6; p =.05). Weight gain during the 4-week treatment periods was greater for risperidone (mean 1.9 kg) than pimozide (1.0 kg). No patient suffered a serious adverse event, but 6 of 19 subjects failed to complete the protocol. Neither medication was associated with ECG changes.
                In this study, risperidone appeared superior to pimozide for tic suppression but was associated with greater weight gain. In a double-blind placebo-controlled study, both pimozide and haloperidol significantly decreased tic frequency in nine patients with Gilles de la Tourette's syndrome. These findings are consistent with the catecholamine hypothesis of tic generation. Pimozide was associated with significantly fewer complaints of lethargy. Follow-up 4-20 months later showed that six of seven patients receiving pimozide and one of two receiving haloperidol had had greater than 75% improvement in symptoms. Preliminary studies suggested that delta-9-tetrahydrocannabinol (THC), the major psychoactive ingredient of Cannabis sativa L., might be effective in the treatment of Tourette syndrome (TS). This study was performed to investigate for the first time under controlled conditions, over a longer-term treatment period, whether THC is effective and safe in reducing tics in TS.
                In this randomized, double-blind, placebo-controlled study, 24 patients with TS, according to DSM-III-R criteria, were treated over a 6-week period with up to 10 mg/day of THC. Tics were rated at 6 visits (visit 1, baseline; visits 2-4, during treatment period; visits 5-6, after withdrawal of medication) using the Tourette Syndrome Clinical Global Impressions scale (TS-CGI), the Shapiro Tourette-Syndrome Severity Scale (STSSS), the Yale Global Tic Severity Scale (YGTSS), the self-rated Tourette Syndrome Symptom List (TSSL), and a videotape-based rating scale.
                Seven patients dropped out of the study or had to be excluded, but only 1 due to side effects. Using the TS-CGI, STSSS, YGTSS, and video rating scale, we found a significant difference (p <.05) or a trend toward a significant difference (p <.10) between THC and placebo groups at visits 2, 3, and/or 4. Using the TSSL at 10 treatment days (between days 16 and 41) there was a significant difference (p <.05) between both groups. ANOVA as well demonstrated a significant difference (p =.037). No serious adverse effects occurred.
                Our results provide more evidence that THC is effective and safe in the treatment of tics. It, therefore, can be hypothesized that the central cannabinoid receptor system might play a role in TS pathology. A clinical trial was undertaken to determine the role of dopaminergic and noradrenergic blockers in the maintenance treatment of remitted schizophrenics. One hundred and six remitted schizophrenic outpatients were treated with one of nine treatments, viz., thioridazine 25 mg or 75 mg, pimozide 2 mg or 6 mg, and their respective combinations, for 1 year in a double-blind controlled study employing a randomized design. The data from a previous study were utilized as a retrospective placebo group. Pimozide prolonged the number of symptom-free days in a dose-dependent manner and did so more markedly than thioridazine. Combined administration of pimozide and thioridazine prolonged the number of symptom-free days to a greater extent than their single administration. However, an inverted U-shaped dose-response curve was obtained with the combined administration of these agents. These data suggest that both the dopaminergic and noradrenergic blocking action of neuroleptics are important in preventing relapse in remitted schizophrenics.
Pimozide is an effective treatment for tics in Tourette Syndrome, though the number of trials comparing its effect to placebo and other drugs is limited. Trials of longer duration (minimum six months) are needed to investigate the longer-term effects of pimozide compared to atypical neuroleptics.  Future trials should use the Yale Global Tic Severity Scale to assess the main outcome measure, and quantify adverse events with the Extrapyramidal Symptoms Rating Scale.