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 treatment of attention-deficit hyperactivity disorder in Tourette's syndrome: a double-blind placebo-controlled study with clonidine and desipramine. Treatment of Tourette's syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial. Pimozide versus fluphenazine in ambulatory schizophrenics: A 12-month comparison study.
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. Because psychostimulants can exacerbate preexisting motor/phonic tics in individuals with Tourette's syndrome (TS), a clinical trial was performed to examine the ability of clonidine and desipramine to modify attention-deficit hyperactivity disorder (ADHD) behaviors in children with TS + ADHD.
                A double-blind, placebo-controlled protocol was used in which each subject served as his or her own control and received, in a randomly assigned fashion, 6-week medication cycles with clonidine (0.05 mg four times daily), desipramine (25 mg four times daily), and placebo.
                Thirty-seven children with TS+ADHD between the ages 7 to 13 years and of normal intellect were recruited, and 34 (31 males, 3 females) completed the entire protocol. Outcome measures for ADHD included Parent and Teacher Child Behavior Checklists (CBCL), continuous performance tests, and neuropsychologic tests of executive function. Several markers for ADHD were shown to improve significantly (P < .05) after treatment with desipramine (parent linear analogue rating, parent CBCL "hyperactivity" subscale, and teacher CBCL subscales "nervous/overactive," "anxious," and "unpopular"). Improvement with desipramine was always superior to that noted with clonidine. Clinical improvement did not correlate with drug blood levels. On measures of tic severity, neither drug made tics worse. Desipramine showed a statistically significant improvement on a global linear analogue scale, but not on the Hopkins Motor/Vocal Tic Severity Scale, the Tourette Syndrome Severity Scale, or the Yale Global Tic Severity Scale. Clonidine did not significantly alter tic severity on any measure.
                The results of this study suggest that desipramine may be a useful alternative for the treatment of symptoms of ADHD in children with TS. Anecdotal reports in Tourette's syndrome (TS) have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive ingredient of marijuana, reduce tics and associated behavioral disorders. We performed a randomized double-blind placebo-controlled crossover single-dose trial of Delta(9)-THC (5.0, 7.5 or 10.0 mg) in 12 adult TS patients. Tic severity was assessed using a self-rating scale (Tourette's syndrome Symptom List, TSSL) and examiner ratings (Shapiro Tourette's syndrome Severity Scale, Yale Global Tic Severity Scale, Tourette's syndrome Global Scale). Using the TSSL, patients also rated the severity of associated behavioral disorders. Clinical changes were correlated to maximum plasma levels of THC and its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). Using the TSSL, there was a significant improvement of tics (p=0.015) and obsessive-compulsive behavior (OCB) (p = 0.041) after treatment with Delta(9)-THC compared to placebo. Examiner ratings demonstrated a significant difference for the subscore "complex motor tics" (p = 0.015) and a trend towards a significant improvement for the subscores "motor tics" (p = 0.065), "simple motor tics" (p = 0.093), and "vocal tics" (p = 0.093). No serious adverse reactions occurred. Five patients experienced mild, transient side effects. There was a significant correlation between tic improvement and maximum 11-OH-THC plasma concentration. Results obtained from this pilot study suggest that a single-dose treatment with Delta(9)-THC is effective and safe in treating tics and OCB in TS. It can be speculated that clinical effects may be caused by 11-OH-THC. A more long-term study is required to confirm these results. In this study, chronic schizophrenic outpatients who had been maintained on various neuroleptics for an average of about 4 years had their previous medications (approximately equivalent to 695 mg of chlorpromazine per day) changed abruptly to either pimozide or fluphenazine given in single daily oral doses on a double-blind basis for a period of 52 weeks. Average daily doses were pimozide 9.6 mg and fluphenazine 12.5 mg. Measurements of the therapeutic effects of the two drugs were made immediately prior to starting the study, at the end of the 2nd and 4th weeks, and thereafter every 4th week to the end of the study. Three psychometric scales were used for evaluation: Brief Psychiatric Rating Scale (BPRS); Evaluation of Social Functioning (ESFR); and Clinical Global Impressions (CGI). In addition, patients participated in a Social Adjustment Inventory (SAI) evaluation. Statistical analysis with the use of several statistical techniques for between- and within-drug group comparisons revealed that pimozide and fluphenazine were equally effective in maintaining control of symptomatology of chronic schizophrenics at a level commensurate with or better than that provided by their previous medication. Side effects were characteristic of marketed neuroleptics, similar in severity and occurrence between study-drug groups, mainly extrapyramidal symptoms, and readily controlled with antiparkinsonian medication. Pimozide, slightly more potent than fluphenazine, proved to be equally effective for the long-term management of chronic schizophrenic patients.
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.