A randomized, double-blind, placebo-controlled trial of metoclopramide for the treatment of Tourette's disorder

OBJECTIVE: The pattern of dopamine antagonism by metoclopramide suggests benefits in the treatment of tic disorders. The purpose of this study was to examine the efficacy and safety of metoclopramide in the treatment of children and adolescents with tic disorders. METHOD: Twenty-seven medication-free patients (age 11.9 +/- 2.7 years) with Tourette's disorder or a chronic tic disorder participated in an 8-week double-blind, randomized, placebo-controlled trial of metoclopramide. Metoclopramide was started at 5 mg daily and titrated as needed to a maximum dose of 40 mg daily. Tics were rated every 2 weeks, and adverse effects, including weight, cardiac, and laboratory measures, were monitored. RESULTS: After 8 weeks of treatment, subjects receiving metoclopramide showed a 39% reduction in their total tic score on the Yale Global Tic Severity Scale, while subjects receiving placebo showed only a 13% reduction in tic severity (p = .001). Metoclopramide was well tolerated with no significant laboratory or cardiac changes noted other than an increase in serum prolactin. CONCLUSIONS: The results of this small controlled study suggest that metoclopramide is an effective and well-tolerated treatment for children and adolescents with tic disorders. Further trials are needed to confirm its efficacy and safety in pediatric patients and adults.     

Tourette's syndrome improvement with pergolide in a randomized, double-blind, crossover trial

OBJECTIVE: To determine whether pergolide, a mixed D1-D2-D3 dopamine agonist, is efficacious and safe in the treatment of children with Tourette's syndrome. BACKGROUND: Neuroleptics, which block dopamine transmission, are currently used for treatment of children with severe tics, but major side effects and limited efficacy reduce clinical utility. Prior open-label reports of pergolide suggest potential benefit. METHODS: The authors enrolled 24 children age 7 to 17 years with Tourette's disorder, chronic motor tic disorder, or chronic vocal tic disorder by Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria, plus severity criteria on the Yale Global Tic Severity Scale (YGTSS) of > or =20, in a double-blind, placebo-controlled, crossover study. Children were randomized to receive either placebo or up to 300 microg/day pergolide for the first 6-week treatment period, with a 2-week placebo washout, followed by crossover to the alternate treatment. The primary outcome measure was tic severity assessed by YGTSS. RESULTS: Compared with placebo treatment, pergolide treatment was associated with significantly lower YGTSS scores (42.0 +/- 20.4 versus 23.5 +/- 18.7; F = 12.0, df = 1, 17, p = 0.0011). No patient had a serious adverse event and pergolide was well tolerated. CONCLUSIONS: In this randomized, placebo-controlled, crossover trial, pergolide appeared to be a safe and efficacious treatment for Tourette's syndrome in children.     

Ondansetron treatment in Tourette's disorder: a 3-week, randomized, double-blind, placebo-controlled study

OBJECTIVE: The aim of the present study was to evaluate the efficacy of ondansetron, a selective 5-HT(3) antagonist, in the treatment of Tourette's disorder. METHOD: Participants (N = 30) aged 12 to 46 years, diagnosed with DSM-IV Tourette's disorder and resistant to previous haloperidol treatment, were enrolled in a 3-week, randomized, double-blind, placebo-controlled outpatient study. Assessments were conducted at baseline and once a week during the study period. Scales used included the Tourette's Syndrome Global Scale (TSGS), the Yale Global Tic Severity Scale (YGTSS), and the Yale-Brown Obsessive Compulsive Scale. Ondansetron dose was 8, 16, and 24 mg/day in the first, second, and third weeks, respectively. RESULTS: A significant positive effect of ondansetron on tic severity, as assessed by the TSGS, was noted (baseline vs. endpoint: mean +/-SD = 29.62 +/-20.33 vs. 20.58 +/-12.82, p = .002 vs. placebo). However, no significant effect was detected upon assessing ondansetron/ placebo effect on tic severity with the YGTSS (baseline vs. endpoint: mean +/-SD = 24.04 +/-9.44 vs. 17.50 +/-9.48, p = .15 vs. placebo). No change in obsessive-compulsive symptoms was noted in either group. Adverse effects included mild and transient abdominal pain. CONCLUSIONS: Ondansetron may have antitic effects in patients with Tourette's disorder. Large-scale, double-blind studies should further assess the antitic efficacy of ondansetron.     

Olanzapine in the treatment of aggression and tics in children with Tourette's syndrome--a pilot study

OBJECTIVE: The aim of this study was to examine the effects of olanzapine on aggressive behaviour and tic severity in children with Tourette's Syndrome (TS). METHOD: Ten (10) subjects (aged 7-13 years) with a primary diagnosis of TS and a history of aggressive behaviour were treated in a single-blind, 2-week placebo run-in, 8-week treatment phase trial. The starting dose of olanzapine was 1.25-2.5 mg/day and was titrated at biweekly intervals, as tolerated. The mean dosage at the end of the trial was 14.5 mg/day. RESULTS: All 10 subjects completed the study. Olanzapine produced clinically and statistically significant reductions of aggression and tic severity from baseline to trial completion, as measured by the Achenbach Child Behavior Checklist (CBCL) and Yale Global Tic Severity Scale (YGTSS). Weight gain during the treatment period was the most common adverse effect (range 2-20 lbs: group mean 12.0 lbs +/- 5.71). No other significant adverse effects were observed during the 10-week trial. CONCLUSION: The results of this trial confirm clinical observations that olanzapine may be an effective treatment for aggression and tics in children with Tourette's syndrome. Olanzapine was generally well tolerated, although significant weight gain was observed throughout the trial.     

Treatment of Tourette's syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial

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.     

Efficacy of Glutamate Modulators in Tic Suppression: A Double-Blind,Randomized Control Trial of D-serine and Riluzole in Tourette Syndrome

BackgroundIt has been hypothesized that glutamatergic transmission may be altered in Tourette syndrome. In this study, we explored the efficacy of a glutamate agonist (D-serine) and antagonist (riluzole) as tic-suppressing agents in children with Tourette syndrome.MethodsWe performed a parallel three-arm, 8-week, double-blind, randomized placebo-controlled treatment study in children with Tourette syndrome. Each child received 6 weeks of treatment with D-serine (maximum dose 30 mg/kg/day), riluzole (maximum dose 200 mg/day), or placebo, followed by a 2-week taper. The primary outcome measure was effective tic suppression as determined by the differences in the Yale Global Tic Severity Scale score; specifically, the total tic score and the combined score (total tic score + global impairment) between treatment arms after 6 weeks of treatment. Mann-Whitney U tests were performed to analyze differences between each group and the placebo group.ResultsTwenty-four patients (males = 21, ages 9-18) enrolled in the study; one patient dropped out before completion. Combined Yale Global Tic Severity Scale score and total tic scores improved in all groups. The 6-week mean percent improvement of the riluzole (n = 10), D-serine (n = 9), and placebo (n = 5) groups in the combined Yale Global Tic Severity Scale score were 43.7, 39.5, and 30.2 and for total tic scores were 38.0, 25.0, and 34.0, respectively. There were no significant differences in Yale Global Tic Severity Scale score or total tic score, respectively, between the riluzole and placebo (P = 0.35, 0.85) or D-serine and placebo (P = 0.50, 0.69) groups.ConclusionTics diminished by comparable percentages in the riluzole, D-serine, and placebo groups. These preliminary data suggest that D-serine and riluzole are not effective in tic suppression.     

Single-dose pharmacokinetics and safety of ziprasidone in children and adolescents

OBJECTIVE: The purpose of this study was to provide single-dose pharmacokinetic, safety, and tolerability data for ziprasidone in youths with tic disorder, for comparison to adult studies to discern whether ziprasidone pediatric dosing could be modeled from adult data. METHOD: A single-dose, open-label study of ziprasidone was conducted in youths (ages 7-16 years) with Tourette's disorder or chronic tic disorder. Dosing of ziprasidone oral suspension (40 mg/mL) was weight adjusted: >60 kg, 20 mg (group 1, n = 8); 31 to 60 kg, 10 mg (group 2, n = 8); and 16 to 30 kg, 5 mg (group 3, n = 8). Patients were assessed for serum ziprasidone concentration, safety, tolerability, and electrocardiogram pre- and postdose. RESULTS: Twenty-four patients were evaluated for safety and tolerability, and 23 were evaluated for pharmacokinetics. Regression analysis of AUC(0-infinity) and Cmax values versus weight-normalized dose showed linear, dose-related changes in ziprasidone exposure. Ziprasidone was well tolerated with frequent, although transient, somnolence. No clinically significant change from baseline was observed in Bazett's or Fridericia's corrected QT(c) interval, and change in QT(c) interval was not related to serum ziprasidone concentration. CONCLUSIONS: Oral ziprasidone exhibited linear pharmacokinetics and dose-related exposure in youths with Tourette's disorder or chronic tic disorder, which are comparable to adult data. A single dose of ziprasidone was well tolerated without clinically significant effects on electrocardiograms collected around the time of maximum serum concentration.     

Tic reduction with risperidone versus pimozide in a randomized, double-blind, crossover trial

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: In this study, risperidone appeared superior to pimozide for tic suppression but was associated with greater weight gain.     

Risperidone versus clonidine in the treatment of children and adolescents with Tourette's syndrome

OBJECTIVE: To evaluate the efficacy and tolerability of risperidone in comparison with clonidine in the treatment of children and adolescents with Tourette's syndrome (TS). METHOD: Following a 7- to 14-day single-blind, placebo lead-in, 21 subjects aged 7 to 17 years were randomly assigned to 8 weeks of double-blind treatment with clonidine or risperidone. Research scales evaluated tics and comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms. RESULTS: Risperidone and clonidine appeared equally effective in the treatment of tics in an intent-to-treat analysis, as rated by the Yale Global Tic Severity Scale (YGTSS). Risperidone produced a mean reduction in the YGTSS of 21%; clonidine produced a 26% reduction. Among subjects with comorbid obsessive-compulsive symptoms, 63% of the risperidone group and 33% of the clonidine group responded to treatment (not significant). The most common adverse event seen with both treatments was sedation, which was mild to moderate in severity. Sedation subsequently resolved with continued administration of the medication or with a dose reduction. No clinically significant extrapyramidal symptoms were observed. CONCLUSIONS: In this pilot study, risperidone demonstrated efficacy equivalent to clonidine in the treatment of tic symptoms in children and adolescents with TS. Further research is needed to clarify the role of atypical antipsychotics in TS and to delineate potential benefits for comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms.     

A double-blind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention-deficit/hyperactivity disorder

BACKGROUND: Currently, there is no consensus on the best therapeutic approach to chronic tic disorders and comorbid attention-deficit/hyperactivity disorder (ADHD). To address this issue, we evaluated the tolerability and efficacy of the noradrenergic tricyclic antidepressant desipramine hydrochloride in the treatment of children and adolescents with chronic tic disorders and comorbid ADHD. METHODS: Forty-one children and adolescents with chronic tic disorders, including Tourette disorder and comorbid ADHD, were studied in a 6-week, double-blind, placebo-controlled, parallel trial. Desipramine was titrated weekly up to 3.5 mg/kg per day. We rated ADHD and tic symptoms weekly and monitored adverse effects, laboratory findings, and cardiovascular parameters. RESULTS: Treatment with desipramine (mean total daily dose, 3.4 mg/kg per day) was well tolerated without meaningful adverse effects. Desipramine significantly reduced core symptoms of ADHD (ADHD Rating Scale; 42% decrease from baseline relative to placebo, P<.001), with equal response in inattentive symptoms and hyperactive/impulsive symptoms (P<.001 for both). The ADHD response rate was robust (71% vs 0%; desipramine vs placebo, P<.001). Likewise, desipramine significantly reduced tic symptoms (Yale Global Tic Severity Scale; 30% decrease from baseline relative to placebo, P<.001), with equal response in motor and phonic tic symptoms (P<.01 for both). The tic response rate was substantial (58% vs 5%; desipramine vs placebo, P<.001). There were small but statistically significant differences between desipramine and placebo in heart rate and blood pressure. CONCLUSIONS: Treatment with desipramine was well tolerated and was associated with robust clinically significant reductions in tic and ADHD symptoms in children and adolescents with chronic tic disorders and ADHD diagnoses.     

Transdermal nicotine and haloperidol in Tourette's disorder: a double-blind placebo-controlled study.

BACKGROUND: Preclinical animal and open-trial clinical trials using nicotine gum and the transdermal nicotine patch found that treatment with nicotine potentiates the effects of neuroleptics in reducing the dyskinetic symptoms of Tourette's disorder. We sought to verify and expand these findings in a prospective double-blind placebo-controlled trial. METHOD: Seventy patients with DSM-IV Tourette's disorder were treated with either transdermal nicotine (7 mg/24 hours) or placebo patches in a 33-day, randomized, double-blind study. Each patient received an individually based optimal dose of haloperidol for at least 2 weeks prior to random assignment to nicotine or placebo treatment. A new patch was worn each day for the first 5 days. On the sixth day, the dose of haloperidol was reduced by 50%. Daily patch applications were then continued for an additional 2 weeks (through day 19), at which time the patch was discontinued, but the 50% dose of haloperidol was continued for an additional 2 weeks (through day 33). Clinical and safety assessments were made at each visit. RESULTS: Patients who completed all 19 days of nicotine (N = 27) or placebo (N = 29) patch treatment were used in efficacy analyses. As documented by the Clinician- and Parent-rated Global Improvement scales, transdermal nicotine was superior to placebo in reducing the symptoms of Tourette's disorder. The Yale Global Tic Severity Scale was less sensitive in detecting a placebo/drug difference than were the global improvement scores, suggesting that some of the improvement may not have been related to treatment-related changes in tic severity, but to the emotional and behavioral symptoms. The side effects of nausea and vomiting were significantly more common in the nicotine group (71% [N = 25] and 40% [N = 14]) than in the placebo group (17% [N = 6] and 9% [N = 3]) (nausea, p = .0001; vomiting, p = .004). CONCLUSION: Transdermal nicotine was superior to placebo in reducing behavioral symptoms when patients were receiving an optimal dose of haloperidol, when the dose of haloperidol was reduced by 50%, and when the patch had been discontinued for 2 weeks. These findings confirm earlier open-label findings and suggest that combining nicotinic receptor modulation and neuroleptics could be a therapeutic option for the treatment of Tourette's disorder. While side effects limit chronic use of nicotine, it may be useful on a p.r.n. basis. Further clinical research is warranted to investigate the use of novel nicotinic receptor modulating agents with improved safety profiles over nicotine.     

Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group

BACKGROUND: This 7-day, randomized, open-label, multicenter, international study compared the efficacy and tolerability of intramuscular (i.m.) ziprasidone with haloperidol i.m. and the transition from i.m. to oral treatment in hospitalized patients with acute psychotic agitation (related to DSM-III-R diagnoses). METHOD: Patients received up to 3 days of flexible-dose ziprasidone i.m. (N = 90) or haloperidol i.m. (N = 42) followed by oral treatment to day 7. After an initial ziprasidone i.m. dose of 10 mg, subsequent i.m. doses of 5 to 20 mg could be given every 4 to 6 hours (maximum daily dose = 80 mg) if needed, followed by oral ziprasidone, 80-200 mg/day. Haloperidol i.m. doses of 2.5 to 10 mg were given on entry, followed by 2.5 to 10 mg i.m. every 4 to 6 hours (maximum daily dose = 40 mg) if needed, then by oral haloperidol, 10-80 mg/day. RESULTS: The mean reductions in Brief Psychiatric Rating Scale (BPRS) total, BPRS agitation items, and Clinical Global Impressions-Severity scale scores were statistically significantly greater (p < .05, p < .01, and p < .01, respectively) after ziprasidone i.m. treatment compared with haloperidol i.m. treatment. Further reductions in these scores also occurred in both groups following transition to oral treatment. Ziprasidone was associated with a lower incidence of movement disorders and a reduced requirement for anticholinergic medication during both i.m. and oral treatment compared with haloperidol. Movement disorder scale scores improved with ziprasidone i.m. and oral treatment, but deteriorated with haloperidol. Other adverse events were rare with both treatments. CONCLUSION: Ziprasidone i.m. was significantly more effective in reducing the symptoms of acute psychosis and was better tolerated than haloperidol i.m., particularly in movement disorders. The transition from ziprasidone i.m. to oral ziprasidone was effective and well tolerated.     

Striatal dopaminergic D2 receptor occupancy and clinical efficacy in psychosis exacerbation: a 123I-IBZM study with ziprasidone and haloperidol

OBJECTIVE: The aim of this study was to compare striatal dopaminergic D2 receptor occupancy (D2 RO) induced by ziprasidone and haloperidol and its relationship with clinical response and extrapyramidal side effects (EPS) in patients with acute psychosis exacerbation. METHOD: Twenty patients hospitalized with an acute psychosis exacerbation were randomised in a single-blind study to receive either ziprasidone (80-120 mg/day) or haloperidol (5-20 mg/day) for more than 2 weeks. When stable doses were achieved, data on 123I-IBZM single-photon emission computed tomography (SPECT), as well as data on clinical efficacy (positive and negative symptoms scale [PANSS]) and EPS (Simpson Angus scale [SAS]), were compared between the two groups of patients. Clinical response was defined as a percentage of change of >30% in PANSS. Striatal D2 RO and clinical data were also compared between responders and nonresponders on each treatment group. RESULTS: All patients on haloperidol and four patients on ziprasidone showed EPS. Mean D2 RO was significantly higher in the haloperidol (74.7+/-3.5) than in the ziprasidone (60.2+/-14.4) group (Mann Whitney U-test [M-W U-test] 8.50; p=0.002). Five patients were responders, and five were nonresponders on each group of treatment. Haloperidol responders and nonresponders did not differ in D2 RO, duration of treatment, doses or EPS. Ziprasidone responders were on higher doses than nonresponders and showed higher D2 RO although below 74%. A positive correlation of ziprasidone D2 RO was found with dose (r Spearman 0.87; p=0.001) and with SAS scores (r Spearman 0.88; p=0.001). CONCLUSIONS: Ziprasidone induces lower D2 RO and EPS than haloperidol, which is consistent with an atypical antipsychotic profile. A direct relationship of ziprasidone D2 RO with dose, clinical efficacy and EPS has been found in this study. These data suggest that high ziprasidone doses might be more beneficial in patients with psychosis exacerbation and claim for caution regarding EPS appearance with such high dosages.     

A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia

BACKGROUND: Ziprasidone is a novel antipsychotic with a unique pharmacologic profile. This study compared ziprasidone with the conventional antipsychotic haloperidol in outpatients with stable schizophrenia. METHOD: Three hundred one outpatients with stable chronic or subchronic schizophrenia (DSM-III-R) were randomized and participated in this double-blind, multicenter, parallel-group clinical study comparing flexible-dose oral ziprasidone, 80-160 mg/day (N = 148), with haloperidol, 5-15 mg/day (N = 153), over 28 weeks. Patients were assessed using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions-Severity of Illness scale, the Montgomery-Asberg Depression Rating Scale, the Simpson-Angus Scale, the Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale. RESULTS: Modal doses at endpoint were 80 mg/day for ziprasidone and 5 mg/day for haloperidol. Improvements in all mean efficacy variables with both ziprasidone and haloperidol were observed. Significantly more patients were categorized as negative symptom responders (> or = 20% reduction in PANSS negative subscale score) in the ziprasidone group (48%) compared with the haloperidol group (33%) (p < .05). Ziprasidone had clear advantages over haloperidol in all evaluations of movement disorders. Changes in body weight were negligible with both treatments. No pattern of laboratory or cardiovascular changes was observed. CONCLUSION: Ziprasidone and haloperidol were both effective in reducing overall psychopathology; ziprasidone demonstrated effective treatment of negative symptoms and was better tolerated than haloperidol. Ziprasidone appears to offer an effective alternative to haloperidol in the long-term treatment of stable outpatients with schizophrenia.     

Effectiveness and safety of risperidone for children and adolescents with chronic tic or tourette disorders in Korea

The aim of this 6-week, open-label design study was to determine the short-term effectiveness and safety of risperidone as an alternative for traditional antipsychotic drugs in the treatment of chronic tic disorder or Tourette's Disorder in young children and adolescents. The subjects were 15 young children and adolescents (the ratio of male:female subjects was 13:2 and their mean age was 10 +/- 2.4 years). Seven subjects were diagnosed with Tourette's Disorder and 8 subjects with chronic tic disorder, and all subjects were administered risperidone without hospitalization. Of the 15 subjects, 1 subject had a comorbid disorder (obsessive compulsive disorder), but no subject had a previous history of psychiatric hospitalization. Ten of the 15 subjects were administered risperidone for the first time, and 5 of the 15 subjects had been previously treated with traditional drugs (haloperidol or pimozide). Clinical responses were measured at baseline and after 1, 3, and 6 weeks of drug treatment by using the Korean version of the Yale Global Tic Severity Scale and the Global Assessment of Functioning Scale. Side effects were carefully monitored using adverse event evaluation charts. The mean dosage of risperidone was 0.53 +/- 0.13 mg on the 1st week, 0.90 +/- 0.28 mg on the 3rd week, and 1.23 +/- 0.37 mg on the 6th week. Comparison between periods according to the Korean version of the Yale Global Tic Severity Scale showed significant differences (t = 4.920; df = 14; p < 0.01) during the 1st- to 3rd-week period. After 6 weeks of administration, the tic severity scale showed a 36% reduction in the overall tic symptom scores and 13 of the 15 subjects showed significant improvement, 1 subject showed no difference in symptoms, and, for 1 subject, the symptoms worsened. Also, the mean Global Assessment of Functioning Scale score was 66.8 +/- 10.8 at baseline and improved to a mean of 73.1 +/- 10.1 after 6 weeks of treatment. Regarding side effects, only 1 case reported sedation, but drug administration was continued because the degree was mild. The results of this study show that, risperidone, a potent combined serotonin (5-HT2) and dopamine (D2) receptor antagonist, is both effective and safe for the treatment for Tourette's Disorder and chronic tic disorder in children and adolescents.     

Intramuscular ziprasidone, 2 mg versus 10 mg, in the short-term management of agitated psychotic patients

BACKGROUND: There is a clear need for effective, well-tolerated intramuscular (i.m.) agents for the acute control of agitated psychotic patients. Currently used agents, including conventional antipsychotics and/or benzodiazepines, may be associated with distressing side effects such as extrapyramidal side effects and excessive sedation. OBJECTIVE: The objective of this study was to evaluate the efficacy and tolerability of the rapid-acting i.m. formulation of the novel antipsychotic ziprasidone in the treatment of inpatients with psychosis and acute agitation (DSM-IV diagnoses). METHOD: In a 24-hour, double-blind, fixed-dose clinical trial, patients were randomly assigned to receive up to 4 injections (every 2 hours p.r.n.) of 2 mg (N = 54) or 10 mg (N = 63) of ziprasidone i.m. The Behavioral Activity Rating Scale measured behavioral symptoms at baseline and the response to treatment up to 4 hours after the first i.m. injection. RESULTS: Ziprasidone i.m., 10 mg, rapidly reduced symptoms of acute agitation and was significantly more effective (p < .01) than the 2-mg dose up to 4 hours after the first injection. Patients were calmed but not excessively sedated, and over half were classed as responders 2 hours after the 10-mg dose. No acute dystonia or behavioral disinhibition was reported. One patient who received the 10-mg dose experienced the extrapyramidal side effect akathisia. CONCLUSION: Ziprasidone i.m., 10 mg, is rapidly effective and well tolerated in the short-term management of the agitated psychotic patient. Comparison with a study of identical design comparing 2-mg with 20-mg doses in patients with similar levels of psychopathology suggests that efficacy with 10 mg or 20 mg of ziprasidone i.m. is significant and dose related.     

Factor-analytic study of the Yale Global Tic Severity Scale

We report on the factor structure of the Yale Global Tic Severity Scale. Participants were 76 children and adolescents diagnosed with tic disorders. Overall, the model proposed by Leckman et al. [Leckman, J.F., Riddle, M.A., Hardin, M.T., Ort, S.I., Swartz, K.L., Stevenson, J., Cohen, D.J., 1989. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. Journal of the American Academy of Child and Adolescent Psychiatry 28, 566-573.] represented an adequate fit. The internal consistency of the factors was acceptable and the convergent and divergent validity was supported vis-à-vis correlations with parent ratings of Tourette's Disorder symptoms. These findings support the use of the original scoring structure in assessing pediatric tic severity.     

The validity of instruments measuring tic severity in Tourette's syndrome.

By using four different scales that measure tic severity in Tourette's syndrome, three independent judges concurrently evaluated their validity and interjudge reliability in 20 affected individuals. The Yale Global Tic Severity Scale, Tourette's Syndrome Severity Scale, Tourette's Syndrome-Clinical Global Impression Scale, and the Hopkins Motor and Vocal Tic Scale were equally effective in determining overall severity and showed good interrater reliability. Both historical information and direct observation of the subject were shown to have a significant contribution towards the overall assessment of tic severity. With all instruments, tic symptom ratings were shown to be independent of those for either attention-deficit hyperactivity disorder or obsessive-compulsive disorder. A 67% incidence of behavioral problems and social difficulties was identified by the Child Behavior Checklist. Nevertheless, associations with tic severity were limited to areas showing interference with social relationships and school adjustments. These results extend the understanding of Tourette's syndrome severity scales and provide additional information necessary for the development of a unified rating scale.     

Quetiapine treatment of children with Tourette's syndrome: report of two cases.

Two children with Tourette's syndrome and comorbid disorders were treated with quetiapine, an atypical antipsychotic successfully used in patients with psychoses and schizophrenia with low incidence of extrapyramidal side effects. Clinical observations and standardized rating scales suggested that this drug produced beneficial effects on tics and other symptoms. Adverse effects (at low doses) were minimal. Because it was suggested that tic efficacy of the newer antipsychotics was related to higher D2 occupancy (with the exception of quetiapine and clozapine, which have relatively low D2 activity), it is hypothesized that tic patients are D2 sensitive and need lower doses of medications. These children were treated naturalistically and were reported retrospectively because of their encouraging outcomes. However, these findings should be interpreted with caution, because no contrast groups, drug withdrawal, or placebo were utilized. Controlled studies are needed to determine the efficacy of quetiapine in the treatment of Tourette's syndrome.     

The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity

Despite the overt nature of most motor and phonic tic phenomena, the development of valid and reliable scales to rate tic severity has been an elusive goal. The Yale Global Tic Severity Scale (YGTSS) is a new clinical rating instrument that was designed for use in studies of Tourette's syndrome and other tic disorders. The YGTSS provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms. Data from 105 subjects, aged 5 to 51 years, support the construct, convergent, and discriminant validity of the instrument. These results indicate that the YGTSS is a promising instrument for the assessment of tic severity in children, adolescents and adults.