Melatonin treatment for tardive dyskinesia: a double-blind, placebo-controlled, crossover study.

BACKGROUND: Antipsychotics remain the mainstay of drug intervention in the management of schizophrenia. However, long-term treatment with antipsychotics is associated with a variety of movement disorders, the most disabling of which is tardive dyskinesia (TD), which occurs in up to 50% of patients hospitalized with chronic schizophrenia. The pathophysiology of TD is still unclear and no definite treatment exists. Both dopamine receptor supersensitivity and oxidative stress-induced neurotoxicity in the nigrostriatal system are apparently implicated. The pineal hormone melatonin is a potent antioxidant and attenuates dopaminergic activity in the striatum and dopamine release from the hypothalamus. Thus, it may have a beneficial effect for both the treatment and prevention of TD. METHODS: Using a double-blind, placebo-controlled, crossover study, we evaluated the efficacy of 10 mg/d of melatonin for 6 weeks in 22 patients with schizophrenia and TD. The primary outcome measure was the change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. RESULTS: The decrease (mean +/- SD) in AIMS score was 2.45 +/- 1.92 for the melatonin and 0.77 +/- 1.11 for the placebo treatment groups (P<.001). No adverse events or side effects were noted. CONCLUSION: This is the first clinical evidence for efficacy of melatonin in the treatment of TD.     

Treatment of tardive dyskinesia with ceruletide: a double-blind, placebo-controlled study.

The effectiveness of a once-weekly i.m. injection of ceruletide (0.8 microgram/kg) in suppressing the symptoms of neuroleptic-induced tardive dyskinesia (TD) was evaluated in a double-blind, placebo-controlled, matched-pairs study. Global evaluation of the severity of TD symptoms over the 8-week study period revealed a significant improvement with ceruletide as compared with placebo. Analysis of the therapeutic response to ceruletide over the course of treatment revealed a slow, but long-lasting improvement of TD symptoms. Side effects, which were mild and transient, consisted mainly of nausea and epigastric discomfort. The incidence of side effects did not differ between the ceruletide- and placebo-treated groups. Ceruletide appears to be a novel and practical treatment that can substantially alleviate the symptoms of dyskinesia.     

The effect of ceruletide on tardive dyskinesia: a double-blind placebo-controlled study

1. In a double-blind placebo-controlled study of 37 patients with tardive dyskinesia, the therapeutic effect of ceruletide was evaluated. 2. The patients were assigned at random to two groups that received either intramuscular injections of 0.8 micrograms/kg of ceruletide or placebo once weekly for 4 weeks. Conventional neuroleptic medication was not changed 3 weeks prior to and throughout the study period. Tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale over an 8-week period. 3. Ceruletide had a more pronounced effect on TD than the placebo however, because of the limited number of subjects examined, the difference between the two groups was not significant. Ceruletide was more effective than placebo in patients under 60 years of age (p less than 0.05) and whose antipsychotic medication was mainly butyrophenones. 4. No serious side effect was noted. 5. The findings suggested that ceruletide therapeutically benefits patients with tardive dyskinesia.     

Risperidone in children with autism: randomized, placebo-controlled, double-blind study

Some open-label studies suggest that risperidone can be useful in the treatment of certain target symptoms in children with autism. We aimed to study whether the use of risperidone in comparison with placebo improved functioning in children with autism with regard to behavior (aggressiveness, hyperactivity, irritability), social and emotional responsiveness, and communication skills. We conducted a randomized, double-blind, placebo-controlled trial with 40 consecutive children with autism, whose ages ranged from 2 to 9 years, who were receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6 months. Autism symptoms were monitored periodically. The outcome variables were total scores on the Childhood Autism Rating Scale (CARS) and the Children's Global Assessment Scale (CGAS) after 6 months. Of the 40 children enrolled, 39 completed the trial over a period of 18 months; 19 received risperidone, and 20 received placebo. In the risperidone group, 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Children's Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Children's Global Assessment Scale score in the placebo group (P < .001 and P = .035, respectively). Risperidone also improved social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression. Risperidone was associated with increased appetite and a mild weight gain, mild sedation in 20%, and transient dyskinesias in three children. Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism and was well tolerated.     

Vitamin E in the treatment of tardive dyskinesia: a double-blind placebo-controlled study.

The authors compared vitamin E with placebo in a double-blind randomized crossover study of 27 patients with tardive dyskinesia. Each treatment period lasted for 6 weeks. Vitamin E showed no differences from placebo in the treatment of tardive dyskinesia.     

Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study

We evaluated the effects of amantadine on levodopa-induced dyskinesia (LID) in eighteen consecutive Parkinson's disease (PD) patients in a randomized, double-blind, placebo-controlled study. The primary outcomes were the Clinical Dyskinesia Rating Scale (CDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) part IVa score changes. The secondary outcomes were the UPDRS II and III score changes. Amantadine did not change the CDRS score for hyperkinesia or dystonia, but decreased the duration of LID and its influence on daily activities (p=0.04) and the UPDRS II score (p=0.01) more than placebo. These findings show that amantadine reduces the duration of LID and improves motor disability in PD.     

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.     

褪黑素治疗迟发性运动障碍的随机对照研究

目的 观察褪黑素治疗慢性精神分裂症患者迟发性运动障碍(TD)的临床疗效和不良反应.方法 选择76例有迟发性运动障碍的精神分裂症住院患者,按照入组顺序用随机数字表将患者分为褪黑素治疗组(以下简称褪黑素组,39例)和对照组(37例).褪黑素组患者每晚服用褪黑素1次(9 mg/次),对照组患者只维持常规治疗;观察期均为12周.76例患者治疗前和治疗第4,8,12周末盲法采用异常不自主运动量表(AIMS)评定TD疗效,采用治疗中需处理的不良反应症状量表(TESS)评定不良反应.结果 治疗第4,8,12周末,对照组患者AIMS总分较治疗前的差异均无统计学意义(配对t检验,P均>0.05);褪黑素组患者AIMS总分均较治疗前显著降低,差异有统计学意义(配对t检验,P均<0.05),治疗第12周末舌部、上肢的TD症状较治疗前显著降低,差异均有统计学意义(配对t检验,P均<0.05).治疗第8,12周末两组AIMS总分差异有统计学意义(t检验,P<0.05).褪黑素组和对照组治疗各时点TESS总分与治疗前比较,褪黑素组患者治疗第4,8,12周末较治疗前均显著降低,差异均有统计学意义(配对t检验,P均<0.05);而对照组及两组间的差异均无统计学意义(t检验,P均>0.05).结论 褪黑素治疗慢性精神分裂症患者TD有效,对舌和上肢的症状效果明显,无不良反应.     

The effects of eicosapentaenoic acid in tardive dyskinesia: a randomized, placebo-controlled trial

OBJECTIVE: Worldwide, conventional antipsychotic medication continues to be used extensively, and tardive dyskinesia (TD) remains a serious complication. The primary objective of the present study was to compare the efficacy of EPA versus placebo in reducing symptoms of TD. METHOD: This was a 12-week, double-blinded, randomized study of ethyl-EPA 2g/day versus placebo as supplemental medication, in patients with schizophrenia or schizoaffective disorder, with established TD. RESULTS: Eighty-four subjects were randomized, of whom 77 were included in the analysis. Both the EPA and placebo groups displayed significant baseline to endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores, but there were no significant between-group differences (p=0.4). Response rates (>or=30% improvement in TD symptoms) also did not differ significantly between EPA-treated subjects (45%) and placebo-treated subjects (32%) (p=0.6). However, a post-hoc linear mixed model repeated measures analysis of variance indicated an effect for treatment group and duration of TD. The EPA-treated patients had significantly greater mean reductions in dyskinesia scores initially, although this was not sustained beyond 6 weeks. CONCLUSIONS: This trial failed to demonstrate an anti-dyskinetic effect for ethyl-EPA 2g/day on the primary efficacy measure. However, a modest and transient benefit is suggested in patients with more recent onset of TD. The lack of clear-cut efficacy could be explained on the basis of the dose of EPA being too low, the study being underpowered, TD being too chronic in the majority of cases, differences in dietary fatty acid intake, or that EPA lacks an anti-dyskinetic action.     

Vitamin B(6) in the treatment of tardive dyskinesia: a double-blind, placebo-controlled, crossover study

OBJECTIVE: The authors' goal was to conduct a double-blind trial of vitamin B(6) in the treatment of tardive dyskinesia in patients with schizophrenia. METHOD: Fifteen inpatients with schizophrenia who met research diagnostic criteria for tardive dyskinesia were randomly assigned to treatment with either vitamin B(6) or placebo for 4 weeks in a double-blind crossover paradigm. The Extrapyramidal Symptom Rating Scale was used to assess patients weekly. RESULTS: Mean scores on the parkinsonism and dyskinetic movement subscales of the Extrapyramidal Symptom Rating Scale were significantly better in the third week of treatment with vitamin B(6) than during the placebo period. CONCLUSIONS: Vitamin B(6) appears to be effective in reducing symptoms of tardive dyskinesia.