Multicenter, double-blind, placebo-controlled study of mecamylamine monotherapy for Tourette's disorder

OBJECTIVE: The safety and efficacy of mecamylamine as a monotherapy in children and adolescents with Tourette's disorder (TD) was investigated in an 8-week multicenter, double-blind, placebo-controlled study. METHOD: Eligible subjects included subjects with TD (DSM-IV), with a naturalistic mix of comorbid diagnoses, nonsmokers, aged 8 to 17 years, whose behavioral and emotional symptoms (according to parents) were more disturbing than tics. After a washout period of all psychotropic medication, subjects were randomly assigned to either mecamylamine (n = 29) or placebo (n = 32). Mecamylamine doses ranged from 2.5 to 7.5 mg/day. Primary efficacy measures included the Tourette's Disorder Scale-Clinician Rated (TODS-CR) and 21-point Clinical Global Improvement scale; secondary efficacy measures included the Yale Global Tic Severity Scale and a rage-attack scale (RAScal). RESULTS: Of the 61 subjects who were randomized, 50 (82%) completed at least 3 weeks on medication and 38 (62%) completed the full 8-week trial. Study withdrawals included 12/29 on mecamylamine and 11/32 on placebo. For the total sample, mecamylamine was no more effective than placebo on any of the outcome measures. However, an item analysis of the TODS-CR suggested that mecamylamine may have reduced sudden mood changes and depression in moderately to severely affected subjects. Except for a slight increase in heart rate during the 1st week in both the mecamylamine and the placebo groups, there where no significant mecamylamine-related changes in vital signs, electrocardiogram, complete blood cell count, or blood chemistry values. CONCLUSIONS: Mecamylamine, in doses up to 7.5 mg/day, is well tolerated in children and adolescents, but as a monotherapy it does not appear to be an effective treatment for tics or for the total spectrum of symptoms associated with TD. However, further studies should be conducted to investigate its possible therapeutic effects in subjects with comorbid mood disorders and as an adjunct to neuroleptic medication.     

Randomized,placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia

OBJECTIVE: The study investigated the efficacy and tolerability of ethyl-eicosapentaenoic acid (E-EPA) as add-on treatment in chronic, severe schizophrenia. METHOD: A randomized, parallel-group, double-blind, placebo-controlled, fixed-dose, add-on study was conducted over 12 weeks. Forty patients with persistent symptoms after at least 6 months of stable antipsychotic treatment received E-EPA or placebo, in addition to their existing treatment. RESULTS: At 12 weeks, the E-EPA group had significantly greater reduction of Positive and Negative Syndrome Scale total scores and of dyskinesia scores than the placebo group. CONCLUSIONS: EPA may be an effective and well-tolerated add-on treatment in schizophrenia.     

Vitamin E treatment for tardive dyskinesia. Veterans Affairs Cooperative Study #394 Study Group

BACKGROUND: Several short-term, controlled trials have documented the efficacy of vitamin E in treating tardive dyskinesia. However, the persistent nature of the disease prompted us to perform a multicenter, longer-term trial of vitamin E. METHODS: The study was a prospective, randomized, 9-site trial of up to 2 years of treatment with d-vitamin E (1600 IU/d) vs matching placebo. One hundred fifty-eight subjects with tardive dyskinesia who were receiving neuroleptic medications were enrolled. The blinded assessments performed were clinical (Abnormal Involuntary Movements Scale, Barnes Akathisia Scale, and Modified Simpson-Angus [for Extrapyramidal Symptoms] Scale) and electromechanical assessments of movement disorders, psychiatric status (Brief Psychiatric Rating Scale), and functioning (Global Assessment of Functioning). There were no significant differences in baseline demographic characteristics or in study assessments between the group that received vitamin E and the group that received placebo. RESULTS: Vitamin E was well tolerated and subject compliance with medication was good and similar between treatment groups. One hundred seven subjects (70% of those receiving vitamin E and 66% of subjects receiving placebo) completed at least 1 year of treatment. There were no significant effects of vitamin E on total scores or subscale scores for the AIMS, electromechanical measures of dyskinesia, or scores from the other 4 scales. CONCLUSION: This long-term, randomized trial of vitamin E vs placebo found no evidence for efficacy of vitamin E in the treatment of tardive dyskinesia.     

Vitamin E in the treatment of tardive dyskinesia: the possible involvement of free radical mechanisms

One of the major problems associated with long-term neuroleptic treatment is persistent tardive dyskinesia (TD), for which there is no satisfactory treatment. We have recently proposed that some cases of TD are associated with neuronal dysfunction resulting from excess free radical production occurring during catecholamine metabolism. We therefore decided to assess the efficacy of a powerful free radical scavenging agent, alpha-tocopherol (vitamin E), on the clinical signs of TD. We treated 15 patients with persistent TD with alpha-tocopherol and matched placebo in a randomized crossover design. Patients demonstrated a significant overall reduction in scores on the Abnormal Involuntary Movements Scale (AIMS) after treatment with alpha-tocopherol, but not after placebo. The mean reduction in the AIMS score with alpha-tocopherol was 43 percent, with seven patients showing a greater than 50 percent reduction in their dyskinesia. There was also a trend for a decrease in scores on the Brief Psychiatric Rating Scale, but no change was observed in scores on the Simpson-Angus Scale for Extrapyramidal Side Effects. Our findings are consistent with the possibility that alpha-tocopherol is beneficial in the treatment of some patients with TD, but further research is necessary to establish the efficacy of this agent.     

Randomized trial of safinamide add‐on to levodopa in Parkinson's disease with motor fluctuations

Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add‐on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double‐blind, placebo‐controlled, parallel‐group study was to evaluate the efficacy and safety of safinamide, an α‐aminoamide with dopaminergic and nondopaminergic mechanisms, as add‐on to l ‐dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression‐Change (CGI‐C). At week 24, mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day, 1.37 ± 2.745 hours for safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI‐C were significantly greater in both safinamide groups versus placebo. There were no significant between‐group differences for incidences of treatment‐emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l ‐dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia. © 2013 International Parkinson and Movement Disorder Society     

A randomized, double-blind, placebo-controlled, study of the efficacy and safety of aripiprazole 10, 15 or 20 mg/day for the treatment of patients with acute exacerbations of schizophrenia

This double-blind, multicenter study aimed to investigate the efficacy and safety of aripiprazole 10, 15 or 20 mg/day versus placebo. Patients requiring inpatient hospitalization for acute exacerbation of schizophrenia were randomized to once-daily aripiprazole 10, 15 or 20 mg/day or placebo for 6 weeks. The primary efficacy outcome was the mean change from baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total score (last observation carried forward). Patients with no improvement by Week 3 (Clinical Global Impression-Global Improvement score > or =4) could transfer to open-label aripiprazole 20mg/day. In total, 420 patients were randomized to placebo (n = 108); aripiprazole 10 mg/day (n = 106); 15 mg/day (n = 106); or 20 mg/day (n = 100). Of these, 142 patients (34%) completed 6 weeks of treatment, 131 (31%) discontinued to receive open-label aripiprazole, and 147 (35%) for other reasons. Aripiprazole 10, 15 and 20 mg/day each showed significantly greater improvements from baseline than placebo for all efficacy measures, including PANSS Total, Positive and Negative scores, and the CGI-Severity of Illness score. Significantly greater improvements in PANSS Total score versus placebo were achieved by Week 1 with 10 or 20 mg/day and Week 3 with 15 mg/day. All three doses were well tolerated. Overall, aripiprazole was not associated with clinically meaningful differences in extrapyramidal symptoms, prolactin or weight changes versus placebo. Aripiprazole 10 mg/day is effective and well tolerated for patients experiencing an acute exacerbation of schizophrenia.     

Trial of dextromethorphan/quinidine to treat levodopa‐induced dyskinesia in Parkinson's disease

Background : Nondopaminergic pathways represent potential targets to treat levodopa‐induced dyskinesia in Parkinson's disease (PD). This pilot‐study (NCT01767129) examined the safety/efficacy of the sigma‐1 receptor‐agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa‐induced dyskinesia. Methods : PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2‐week double‐blind, crossover treatment periods, with intervening 2‐week washout. After 14 days, a 2‐hour intravenous levodopa‐infusion was administered. Patient examinations were videotaped before infusion (“off” state) and every 30 minutes during and afterwards until patients returned to “off.” The primary endpoint was dyskinesia‐severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area‐under‐curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical‐change, and adverse‐events. Results : A total of 13 patients were randomized and completed the study (efficacy‐evaluable population). Dyskinesia‐severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area‐under‐curve 966.5 vs 1048.8; P = .191 [efficacy‐evaluable patients]), and significantly lower in a post‐hoc sensitivity analysis of the per‐protocol‐population (efficacy‐evaluable patients with ≥ 80% study‐drug‐compliance, n = 12) when measured from infusion start to 4‐hours post–infusion completion (area‐under‐curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion‐start to return to “off” (13.3 vs 14.9; P = .018 [efficacy‐evaluable patients]). A total of 9 patients rated dyskinesia “much/very much improved” on dextromethorphan/quinidine versus 1‐patient on placebo. Dextromethorphan/quinidine did not worsen PD‐motor scores, was generally well tolerated, and was associated with more frequent adverse events. Conclusion : This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa‐induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society     

长期抗精神病药治疗撤药时的运动障碍

目的：调查撤药出现的运动障碍（ＷＥ－Ｄ）是否为迟发性运动障碍（ＴＤ）的早期征象。方法：７１例精神分裂症病人停药２周,于停药前及停药后第２周末评定迟发性运动障碍量表（Ｓｉｍｐ－ｓｏｎ量表）及阴性症状量表,收集临床资料,并随访半年。结果：无ＴＤ组病人年龄、病程显著低于ＷＥ－Ｄ组及ＴＤ组病人;ＷＥ－Ｄ组与ＴＤ组病人间年龄、病程、抗精神病药治疗持续时间、平均剂量及阴性症状间无显著差异。结论：ＷＥ－Ｄ可能是ＴＤ的一个早期表现或为一隐匿性运动障碍     

Low incidence of persistent tardive dyskinesia in elderly patients with dementia treated with risperidone

OBJECTIVE: The authors studied the incidence of tardive dyskinesia in elderly institutionalized patients with dementia being treated with risperidone. METHOD: After participating in a 12-week multicenter double-blind study during which they received placebo or one of three doses of risperidone, 330 patients (mean age=82.5 years) with Alzheimer's, vascular, or mixed dementia were enrolled in a 1-year open-label study during which they received flexible doses of risperidone. Persistent emergent tardive dyskinesia was defined according to scores on the dyskinesia subscale of the Extrapyramidal Symptom Rating Scale. RESULTS: The mean modal risperidone dose was 0.96 mg/day (SD=0.53), and the median length of risperidone use was 273 days. The 1-year cumulative incidence of persistent emergent tardive dyskinesia among the 255 patients without dyskinesia at baseline was 2.6%. Patients with dyskinetic symptoms at baseline experienced significant reductions in the severity of dyskinesia. Patients who received 0.75-1.5 mg/day of risperidone showed a significant improvement in psychopathologic symptoms over the 1-year period. CONCLUSIONS: Although there was no control group, the observed incidence of persistent tardive dyskinesia with risperidone seemed to be much lower than that seen in elderly patients treated with conventional neuroleptics. The average optimal dose of risperidone in elderly dementia patients was found to be 0.75-1.5 mg/day.     

Safety of the omega-3 fatty acid, eicosapentaenoic acid (EPA) in psychiatric patients: results from a randomized, placebo-controlled trial

Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), are increasingly being used by psychiatric patients. Most studies have concentrated on efficacy aspects, while little is known about their safety and tolerability in psychiatric populations. This study aimed to assess the effects of EPA treatment on body mass, glucose metabolism, lipid profiles, prolactin secretion, bleeding time, haematology and liver functions. Eighty-four subjects with schizophrenia were treated with either EPA 2 g/day or placebo in addition to their antipsychotic medication for 12 weeks, in a randomized, controlled trial. Forty-seven entered a 40-week open-label extension phase of EPA 2 g/day. Seventy-four patients were included in the analysis. Six patients discontinued from the EPA group and 14 in the placebo group. Adverse event reporting was similar for the two groups. While there were no significant between-group differences, in the blinded phase the EPA group showed a significant increase in body mass index (BMI) and bleeding time. In the open-label extension, there was again a modest increase in BMI. Total cholesterol and HDL levels were significantly decreased. EPA 2 g/day is generally well tolerated. Clinicians should be aware of possible increases in bleeding time, as well as changes in weight and lipid metabolism.     

Treatment of tardive dyskinesia with vitamin E.

OBJECTIVE: Vitamin E (alpha-tocopherol), a free-radical scavenger, has been reported to improve symptoms of tardive dyskinesia. The authors attempted to replicate this finding under more controlled conditions in a larger study group. METHOD: Fifteen inpatients and six outpatients with tardive dyskinesia received up to 1600 IU/day of vitamin E for 6 weeks in a double-blind, placebo-controlled crossover study. Abnormal Involuntary Movement Scale (AIMS) examinations of these patients were videotaped and rated independently by two trained raters. Levels of neuroleptic medication and vitamin E were measured during both treatment periods. Eighteen patients who demonstrated high blood levels of vitamin E were included in the data analysis. RESULTS: Vitamin E levels were significantly higher while the patients were receiving vitamin E than while they were receiving placebo. For all 18 patients, there were no significant differences between AIMS scores after receiving vitamin E and AIMS scores after receiving placebo. In agreement with previous studies, however, the nine patients who had had tardive dyskinesia for 5 years or less had significantly lower AIMS scores after receiving vitamin E than after receiving placebo. There were no changes in neuroleptic levels during vitamin E treatment. CONCLUSIONS: Vitamin E had a minor beneficial effect on tardive dyskinesia ratings in a selected group of patients who had had tardive dyskinesia for 5 years or less. This effect was not due to an increase in blood levels of neuroleptic medications.     

长期服抗精神病药病人的隐性运动障碍

目的：评估抗精神病药对迟发性运动障碍（ＴＤ）的掩盖,即隐性运动障碍（ｃｏｖｅｒｔ ｄｙｓｋｉｎｅ－ｓｉａ）状况。方法应用Ｓｉｍｐｓｏｎ运动障碍评分表评定ＴＤ。入组的６９例病人有２３例病人完成了减药之前、停药三周后和再服药四个月后的ＴＤ评定,６９例次检查都给于隶像,并且两个评定者按照录像独立评定ＴＤ是否存在,评定ＴＤ的一致性良好（ＩＣＣ＝０．７５）。结果完成整个调查的２３例病人中,减药前ＴＤ出现率为     

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.     

Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses.

OBJECTIVE: To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia (AD). METHODS: In this double-blind, multicenter study, 487 institutionalized patients with psychosis associated with AD were randomized to placebo or aripiprazole, 2, 5 or 10 mg/day. Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory-Nursing Home (NPI-NH) version Psychosis Subscale score. Secondary measures included NPI-NH Total, Clinical Global Impression-Severity of Illness (CGI-S), Brief Psychiatric Rating Scale (BPRS) Core and Total, and the Cohen-Mansfield Agitation Inventory (CMAI) scores. RESULTS: Aripiprazole 10 mg/day showed significantly greater improvements (mean change [2 x SD]) than placebo on the NPI-NH Psychosis Subscale (-6.87 [8.6] versus -5.13 [10.0]; F = 6.29, df = 1, 422, p = 0.013 by analysis of covariance [ANCOVA]); CGI-S (-0.72 [1.8] versus -0.46 [1.6]; F = 4.68, df = 1, 419, p = 0.031 [ANCOVA]); BPRS Total (-7.12 [18.4] versus -4.17 [21.6]; F = 4.72, df = 1, 399, p = 0.030 [ANCOVA]); BPRS Core (-3.07 [6.9] versus -1.74 [7.8]; F = 7.30, df = 1, 407, p = 0.007 [ANCOVA]); CMAI (-10.96 [22.6] versus -6.64 [28.6]; F = 5.23, df = 1, 410, p = 0.023 [ANCOVA]), and NPI-NH Psychosis response rate (65 versus 50%; chi(2) = 5.52, df = 1, p = 0.019 [CMH]). Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores. Aripiprazole 2 mg/day was not efficacious. Cerebrovascular adverse events were reported: aripiprazole 2 mg/day, N = 1; 5 mg/day, N = 2; 10 mg/day, N = 4; placebo, N = 0. No deaths in any group (aripiprazole 2 mg/day, 3%; 5 mg/day, 2%; 10 mg/day, 7%; placebo, 3%) were considered to be treatment-related. CONCLUSION: Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD, significantly improving psychotic symptoms, agitation, and clinical global impression. However, clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population.     

Tardive dyskinesia in Chinese inpatients with chronic schizophrenia

The objective of the study was to determine the point prevalence of tardive dyskinesia (TD) in Chinese inpatients with chronic schizophrenia and its association with sociodemographic, clinical and treatment variables and other movement disorders. A cross-sectional assessment of a randomly selected cohort of inpatients (n=225; mean age=42+/-7 years) with DSM-IV schizophrenia was employed using standard rating instruments for TD and other drug-induced movement disorders, in addition to catatonia, and psychotic, negative, depressive and obsessive-compulsive symptoms. Using Schooler and Kane's criteria, 15 subjects (6.7%) had TD. Patients with TD were significantly older and significantly fewer of them were taking antiparkinsonian medication than subjects without TD. There was no significant difference between the TD and non-TD groups with respect to other demographic, clinical and treatment variables including sex, age of onset, length of contact with psychiatric services, current antipsychotic dosage, negative symptoms, catatonia and parkinsonism. The results confirmed the low prevalence of TD in patients with chronic schizophrenia compared to those found in Caucasian patients. The study has also replicated the association of TD in Chinese schizophrenia patients with older age but failed to demonstrate any association between TD and other demographic or clinical characteristics including catatonia.     

Topiramate and triptans revert chronic migraine with medication overuse to episodic migraine

OBJECTIVE: This is a randomized, double-blind versus placebo study aimed at evaluating the efficacy of topiramate (TPM) in reducing the number of days with headache and the amount of acute medication taken monthly in patients with chronic migraine with medication overuse. We also studied the efficacy of single triptans available in Italy in interrupting headache crises during preventive treatment. METHODS: The studied sample was made up of 50 subjects: 30 patients were randomized for treatment with TPM, 100 mg/d, and 20 for placebo. Subjects treated with TPM were further randomized to evaluate, in double-blind versus placebo, the efficacy of single triptans available in Italy. The double-blind phase consisted of a titration phase (4 weeks) and of a maintenance phase (8 weeks). OUTCOME MEASURES: The reduction in the number of days with headache per 28 days and the reduction in the amount of acute medication taken per 28 days throughout the clinical trial in the TPM group were compared with those of the placebo group; the number of patients who were pain-free at 2 hours after the triptan intake and the headache recurrence rate in the 22 hours after the pain-free condition in the triptan group were compared with those of the placebo group. We also looked at tolerability profile. RESULTS: The group treated with TPM had a significant reduction in the number of days with headache (P < 0.0001 vs placebo) and in the mean amount of acute medication taken (P < 0.0001 vs placebo); all triptans were superior to placebo; there were no significant differences between different triptans; the analgesic effect of triptans increased throughout the trial. CONCLUSIONS: Topiramate proved to be well tolerated and effective in reverting chronic migraine with medication overuse to episodic migraine.     

Changes in negative symptoms and the risk of tardive dyskinesia: a longitudinal study. UK700 Group

OBJECTIVE: To examine whether the development of tardive dyskinesia (TD) is accompanied by a parallel process of worsening negative symptoms in a longitudinal study. METHOD: A sample of 708 psychotic patients were followed over a period of 2 years, using the Abnormal Involuntary Movement Scale and the Scale for the Assessment of Negative Symptoms (SANS). RESULTS: Of 361 individuals with no prior evidence of dyskinesia, 46 (13%) developed TD by year 2. Independent of the effects of male sex (odds ratio (OR)=2.18, 95% confidence interval: 1.00-4.74), age (OR per quartile group = 1.39, 95% CI: 1.01-1.90), duration of exposure to antipsychotic medication (OR = 2.35 per 8 months, 95% CI: 1.17-4.72) and average SANS score (OR per quartile group = 1.38, 95% CI: 0.99-1.93), worsening of negative symptoms over the 2 previous years was associated with TD onset (OR per quartile group = 1.46, 95% CI: 1.07-2.00). CONCLUSION: The development of TD is linked, independent of the effect of antipsychotics and older age, to an illness-related pathological process, characterized by worsening negative symptoms.     

Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder

BACKGROUND: Aripiprazole is an investigational agent for treating schizophrenia that has a novel pharmacologic profile. The present study investigated the efficacy, safety, and tolerability of aripiprazole and haloperidol compared with placebo. METHOD: A 4-week, double-blind, randomized study, conducted at 36 U.S. centers between July 1997 and June 1998, compared aripiprazole (15 mg/day, 30 mg/day) to placebo, with haloperidol (10 mg/day) as an active control. Fixed doses of each agent were administered from day 1 throughout the study. A total of 414 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomized. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, PANSS positive, PANSS negative, PANSS-derived Brief Psychiatric Rating Scale (BPRS) core, Clinical Global Impressions (CGI)-Severity of Illness, and mean CGI-Improvement scores. Safety and tolerability evaluations included extrapyramidal symptoms (EPS), weight gain, serum prolactin level, and QTc interval. RESULTS: Both doses of aripiprazole and haloperidol, 10 mg, produced statistically significant (p < or = .05) improvements from baseline in PANSS total, PANSS positive, PANSS-derived BPRS core, and CGI-Severity scores and significantly lower CGI-Improvement scores at endpoint, compared with placebo. Aripiprazole, 15 mg, and haloperidol, 10 mg, significantly improved PANSS negative score compared with placebo. Both aripiprazole doses and haloperidol separated from placebo for PANSS total scores at week 2. Unlike haloperidol, aripiprazole was not associated with significant EPS or prolactin elevation at endpoint compared with placebo. There were no statistically significant differences in mean changes in body weight across the treatment groups versus placebo, and no patients receiving aripiprazole experienced clinically significant increases in QTc interval. CONCLUSION: Aripiprazole, effective against positive and negative symptoms, is a safe and well-tolerated potential treatment for schizophrenia and schizoaffective disorder.     

Lack of clinically significant improvement of patients with tardive dyskinesia following phosphatidylcholine therapy

A double-blind controlled study was undertaken to examine the value of phosphatidylcholine as a treatment for tardive dyskinesia (TD) in 19 psychiatric patients. All patients were maintained on their usual psychotropic medication throughout the entire study. In addition, they were given either phosphatidylcholine (30 g/day) or placebo for 6 weeks. Thirteen of the patients received the crossover treatment for 6 weeks, after which 10 of the 13 were continued on the crossover medication for an additional 6 weeks. At the end of the study, 5 patients had received phosphatidylcholine for 12 weeks and another 12 patients had received the drug for only 6 weeks. Plasma and red blood cell choline levels were monitored every 3 weeks as a measure of compliance. Although some patients showed clinical improvement of their TD, the results did not differ significantly between active drug and placebo. This was in spite of a marked elevation of plasma and red blood cell choline (up to 300% for the Lafayette Clinic patients and up to 400% for the patients from the Ypsilanti Regional Psychiatric Hospital) during treatment with phosphatidylcholine. Side effects of the drug included occasional gastrointestinal upsets and diarrhea but, in general, the medication was tolerated very well. The results indicate that large doses of phosphatidylcholine of soya origin are of no clinical value in treating symptoms of TD in spite of very large increases in blood choline.     

Antipsychotic medication treatment for mild hallucinations in Parkinson's disease: Positive impact on long‐term worsening

To test if antipsychotic medication treatment of Parkinson's disease (PD) patients with mild hallucinations and retained insight delays deterioration to delusions or hallucinations without insight. We identified subjects at the time they developed their first hallucination, based on documented progression in their UPDRS thought disorder (TD) score from <2 to 2 (“benign” hallucinations with insight retained). We registered TD scores at follow‐up visits and their hallucination treatment: antipsychotic medication, PD medication reduction, or observation. The primary outcome measure was the time from the first TD = 2 until the TD score worsened to 3 (hallucinations with loss of insight) or 4 (delusions, psychosis). The effect of antipsychotic medication treatment on transition hazard rate was modeled by proportional hazards regression (Cox model) with antipsychotic medication use as a time‐dependent covariate. Of 64 patients, 31 received antipsychotic medication during the study (mean group follow‐up 31 months). Of the 38 subjects who reached endpoint, eight subjects had been treated with antipsychotic medication compared to 30/33 in those not treated with antipsychotic medication. Antipsychotic medication treatment reduced the risk of deterioration [hazard ratio = 0.156, CI = (0.067–0.363), P < 0.0001] compared to treatment without antipsychotic medications. The median time from the introduction of antipsychotic medication to the conversion from TD = 2 to TD > 2 was 39 months in subjects on antipsychotic medication compared to 12 months in patients treated otherwise. Until randomized treatment trials provide definitive information, early antipsychotic medication treatment for mild hallucinations should be considered with the combined goal of improving current hallucinations and reducing risks of later deterioration. © 2008 Movement Disorder Society