A double-blind comparative trial of remoxipride and haloperidol in the treatment of schizophrenia

A multicentre parallel group study was carried out to compare the efficacy and safety of remoxipride, a new antipsychotic drug, with haloperidol in the treatment of acute schizophrenia. Patients were randomly assigned to the two groups and assessments were made under double-blind conditions. Treatment was preceded by a washout period and lasted 6 weeks. Eighty-nine consecutively admitted men and women meeting the Research Diagnostic Criteria for schizophrenia in an acute phase of the illness were treated with remoxipride 75–300 mg b.d. or haloperidol 5–20 mg b.d. The main assessments were changes in scores on the Brief Psychiatric Rating Scale, Krawiecka Rating Scale and Clinical Global Impression. Both neuroleptics produced clinical improvement but there were no significant differences in overall efficacy measurements between the two drugs. There were relatively few unwanted side-effects. There were significantly less extra-pyramidal symptoms and blurred vision with remoxipride, and less constipation with haloperidol. The results indicate that remoxipride is an effective antipsychotic drug with a low incidence of extrapyramidal side-effects.     

Steady-state pharmacokinetics of controlled release and immediate release formulations of remoxipride in patients with chronic schizophrenia

Twenty-four stable, chronic schizophrenic inpatients were entered in a double-blind crossover study designed to compare single dose and steady state pharmacokinetic profiles of an immediate release formulation (IR) 200 mg BID and a controlled release formulation (CR) of remoxipride 400 mg once daily. The rate of absorption of remoxipride CR was significantly lower than the IR formulation andt _max was prolonged from 1.3 to 7.9 h after a single dose and from 2.2 to 6.0 h after repeated dosing. Although the single dose of remoxipride CR was twice as large as the single dose of the IR, theC _max was similar for both formulations after a single dose. However, theC _max at steady state was slightly lower for CR. There was significantly less fluctuation in plasma concentrations at steady state with the CR formulation, although the average plasma concentration of remoxipride IR and CR was similar. The mean relative bioavailability with regard to the amount of remoxipride absorbed after remoxipride CR 400 mg once daily compared to IR 200 mg BID was 97%. It was concluded that the CR formulation is suitable for a once-daily administration from a pharmacokinetic point of view.     

Zotepine in the prevention of recurrence: a randomised, double-blind, placebo-controlled study for chronic schizophrenia

RATIONALE: Zotepine is an antipsychotic drug with proven efficacy for treatment of acute episodes of schizophrenia. Antipsychotic drugs also require to be effective in prevention of recurrence. OBJECTIVE: This trial was designed to compare the effects of zotepine and placebo in the prevention of recurrence of acute episodes in a population of patients with chronic schizophrenia. METHODS: The study was a double-blind, parallel group, 26-week comparison of zotepine (300 mg daily, with fall back to 150 mg if necessary) versus placebo in 121 patients with chronic schizophrenia and a history of recurrence in the previous 18 months. The primary outcome measure was the time to recurrence. Other evaluations included the brief psychiatric rating scale (BPRS), the scale for the assessment of negative symptoms (SANS), the clinical global impression (CGI) severity and improvement scales, and the Simpson and Angus scale for extrapyramidal symptoms (EPS). RESULTS: Fewer zotepine patients experienced recurrence over 26 weeks than placebo patients (4 versus 21, respectively). The estimated 26-week risk of recurrence was six times lower for zotepine than placebo (8.7% versus 52.8%; hazard ratio 0.16, 95% CI 0.053, 0.484; P<0.001). Scores on the BPRS and CGI supported the efficacy of zotepine. There was no difference between the treatments with respect to EPS. CONCLUSIONS: Zotepine is effective in preventing recurrence in patients with chronic schizophrenia. The level of EPS was not different between zotepine and placebo.     

A randomized,controlled, dose-ranging trial of sertindole in patients with schizophrenia

Sertindole is a novel antipsychotic agent with high selectivity for the mesolimbic dopaminergic pathway and nanomolar affinities for dopamine D₂, serotonin 5-HT₂, and norepinephrine NE₁ receptors. This 40-day randomized, placebo-controlled, dose-ranging multicenter study was designed to assess the effect of sertindole on previously neuroleptic-responsive, hospitalized schizophrenic patients (n=205). Sertindole doses began at 4 mg/day and were increased to 8, 12, or 20 mg/day, depending on randomization. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Extrapyramidal symptoms (EPS) were assessed by movement rating scales, EPS-related adverse events, and use of anti-EPS medications. A dose-related improvement was observed for PANSS, BPRS, and CGI, with statistically significant mean differences (P<0.05) between placebo and 20-mg/day sertindole (decreases from baseline of –5.8 versus –16.9 for PANSS, –4.8 versus –10.4 for BPRS, respectively). The differences in CGI final improvement score between placebo and 20-mg/day sertindole were 3.8 versus 2.9, respectively. EPS-related events were comparable in the placebo and sertindole groups. In conclusion, sertindole 20 mg/day was effective, well tolerated, and not associated with significant motor system abnormalities.This study was presented as a podium presentation at the 23rd Annual Meeting of the American College of Neuropsychopharmacology, Honolulu, Hawaii, December 13–17, 1993. Members of the Sertindole Study Group are listed under Acknowledgements     

Pharmacokinetics and effects on prolactin of remoxipride in patients with tardive dyskinesia

The pharmacokinetics of remoxipride, a new selective dopamine-D₂ receptor antagonist with antipsychotic action, was evaluated in eight elderly psychiatric patients with tardive dyskinesia (TD). The daily oral doses of remoxipride were gradually increased from 50 mg per day to 200 mg t.i.d. over 2 weeks. The pharmacokinetics following the initial 50 mg dose (day 1) and the last 200 mg dose (day 15) of the drug were compared in serial samples. Plasma prolactin concentrations were assessed at the same time points. The area under the total plasma concentration versus time curves (AUC) of remoxipride increased proportionally with dose from day 1 to 15. The mean dose corrected AUC values for the total concentrations were 96.8 at day 1 (4×24.2, 50 mg single oral dose) and 92.2 µmol·h/l at day 15 (200 mg). The unbound fraction of remoxipride calculated on AUC was slightly higher on day 15 (20%) than on day 1 (15%) (P<0.05), indicating slightly concentration-dependent protein binding of the drug. The mean elimination half-life of total remoxipride was slightly longer on day 15 than day 1 (7.5 versus 5.3 h,P<0.01) The corresponding half-lives for the unbound concentrations were 6.4 and 3.9 h, respectively (P<0.01). The pharmacokinetics of remoxipride is similar in these TD patients and in non-TD patients in previous studies. Following repeated administration of remoxipride, tolerance to the prolactin-releasing action of remoxipride is observed. In plots of the relationship between the concentration of remoxipride and the prolactin increase during a dosage interval, the curve on day 15 was positioned markedly to the right of that on day 1. This indicates a decreased sensitivity to the prolactin releasing action of remoxipride following continuous treatment.     

Randomized controlled trial of relapse prevention and a standard behavioral intervention with adult smokers

A previously evaluated behavioral intervention (SB) was modified to focus on relapse prevention (RP) in order to improve adult smokers' ability to cope with high-risk situations and maintain abstinence. Treatment-seeking smokers (N=79) working at four mid-sized businesses attended either an SB (n=38) or an RP intervention (n=41). Both interventions consisted of 6 and 90-min sessions over 8 weeks and included nicotine replacement therapy. Immediately following the interventions, 42.1% of the SB group and 41.5% of the RP group were abstinent (p=.95). The one-year point-prevalence abstinence rates were 28.9% in the SB group and 17.1% in the RP group (p=.21). As there were no significant group differences on abstinence at follow-up, the RP intervention was not found to be more efficacious than a standard behavioral intervention among treatment-seeking adult smokers. Motivation, on the other hand, was a significant predictor of short- and long-term abstinence.     

Towards consensus in the long-term management of relapse prevention in schizophrenia

APPROACH TO DEVELOPING GUIDANCE: When developing guidance for the long-term management of schizophrenia, one approach is to adopt a proactive strategy that sets out clear treatment goals and strategies. This should involve a broad view being taken, embracing overall mental and physical well-being rather than simply the absence of illness. Although relapse prevention is an important goal of any long-term management strategy, there are other aspects that need to be considered, such as reintegration into society, regaining independence and quality of life. CURRENT TREATMENT: To help achieve these goals, a range of interventions can be incorporated into long-term management strategies for schizophrenia, including pharmacological interventions, psychosocial therapies and alliance-building initiatives. The current UK National Institute for Clinical Excellence guidelines already recommend that continuous therapy should be practised using an atypical (second-generation) antipsychotic drug, whenever possible, in preference to older typical drugs. The launch of the first long-acting atypical antipsychotic is an interesting new advance that may benefit many patients with schizophrenia. Psychosocial interventions, particularly family-based therapies, as well as cognitive behavioural and compliance therapies, when used alongside antipsychotics, have been shown to reduce relapse rates dramatically and to assist in social reintegration. In addition, forging collaborative alliances with patients and their carers can help to demystify schizophrenia and empower patients to take responsibility for their illness. CONSENSUS STATEMENT: This article outlines a consensus reached by a panel of leading UK healthcare professionals working with schizophrenia brought together to discuss long-term management strategies.     

A cognitive behavioral smoking abstinence intervention for adults with chronic pain: A randomized controlled pilot trial

Current evidence suggests it may be difficult for patients with chronic pain to quit smoking and, based on previous formative work, a 7-session individual and group-based cognitive behavioral (CB) intervention was developed. The primary aim of this randomized controlled pilot trial was to test the hypothesis that abstinence at month 6 would be greater among patients with chronic pain who received the CB intervention compared to a control condition. Upon admission to a 3-week interdisciplinary pain treatment (IPT) program, patients were randomized to receive the CB intervention (n = 30) or the control condition (n = 30). The 7-day point prevalence of self-reported smoking status was assessed at week 3 (upon completion of the 3-week IPT program) and at month 6 in an intent-to-treat analysis. At week 3, 30% (n = 9) of patients in the CB condition were abstinent from smoking compared to 10% (n = 3) in the control group (P = .104). At month 6, 20% (n = 6) of patients who received the CB intervention were abstinent compared to none in the control group (P = .024). At week 3, a significant group by time interaction effect was found where the CB patients experienced greater improvements in self-efficacy from baseline compared to the control group (P = .002). A greater proportion of patients randomized to the CB group completed the IPT program (P = .052). The findings of this pilot trial suggest that integration of a CB-based smoking abstinence intervention into ongoing pain therapy may be an effective treatment for smokers with chronic pain.     

A controlled trial of intermittent oral acetylcysteine in the long-term treatment of chronic bronchitis

Summary In 69 out-patients with chronic bronchitis in 6 centres the effects of acetylcysteine 600 mg daily, 3 days a week for 6 months, and a placebo have been compared in a double-blind controlled trial. Thirty-five patients were treated with the mucolytic and 34 with the dummy preparation. In the former the clinical course of the chronic bronchitis improved to a greater extent and a significantly lower number of exacerbations was observed. The advantages of long-term oral treatment with the mucolytic in chronic bronchitis suggest that it may be useful as an alternative to long-term antibiotic prophylaxis, or to complement brief courses of antibiotics, in addition to the usual physiotherapy.With the collaboration of:A. Rossi and L. Bergamaschi (Pavia), D. Dei (Udine), G.C. Mereto (Genova), G. Radaelli (Milano), G. Piazza (Mortara), G. Frigerio and G. Damonte (Bresso-Milano)     

A randomized controlled trial of Structural Ecosystems Therapy for HIV medication adherence and substance abuse relapse prevention

Background

Substance abuse in women with HIV/AIDS overshadows other priorities, including health care. Substance abuse may cause women to avoid health care systems and not adhere to their medication regimen.

Methods

A randomized controlled trial tested the efficacy of Structural Ecosystems Therapy (SET) relative to a psychoeducational Health Group (HG) in 126 HIV+ women in recovery. SET, a 4-month intervention, focused on building family support for relapse prevention and HIV medication adherence. Over 12-month follow-up, women were assessed for drug use and medication adherence every 2 months; CD4 T-cell count and HIV viral load were assessed every 4 months.

Results

Levels of drug use did not differ by condition. There was a significant difference in curvature of the rates of change in drug use with SET increasing and then decreasing and HG decreasing and then increasing. Women in SET were more likely to increase substance abuse services in response to relapse and separate from drug using household members than were women in HG. These two changes explained the decline in drug use observed within SET between 6 and 12 months. SET showed declines in medication adherence but increases in CD4 T-cell count relative to HG. The increase in CD4 T-cell count in SET was related to increasing proportions of women in SET taking antiretroviral medications.

Conclusion

The results of the trial were mixed. Women in SET did not show better drug use or medication adherence outcomes, but did show improvement in CD4 T-cell count and theoretical mechanisms of action on drug relapse.     

Self treatment with one of three self selected, ultramolecular homeopathic medicines for the prevention of upper respiratory tract infections in children. A double-blind randomized placebo controlled trial

AIMS: Homeopathic medicines are frequently purchased over the counter (OTC). Respiratory complaints are the most frequent reason for such purchases. Children with upper respiratory tract infection (URTI) are frequent users of homeopathy. This study investigates the effect of self treatment with one of three self selected ultramolecular homeopathic medicines for the prevention of childhood URTI. METHODS: A double-blind randomized parallel group placebo controlled trial was carried out in 251 children below the age of 10 years, recruited by post from those previously diagnosed with URTI when attending a casualty department. The children were randomly assigned to receive either placebo or ultramolecular homeopathic medicines in C-30 potency (diluted 10(-60)) administered twice weekly for 12 weeks. Parents chose the medicine based on simplified constitutional indications for the three medicines most frequently prescribed by Norwegian homeopaths for this group of patients. The main outcome measure relates to the prevention of new episodes of URTI measured with median total symptom score over 12 weeks. RESULTS: There was no difference in the predefined primary outcome between the two groups (P = 0.733). Median URTI scores over 12 weeks in the homeopathic medicine group were 26.0 (95% confidence interval (CI) 16.3, 43.7) and for placebo 25.0 (95% CI 14.2, 38.4). There was no statistical difference between the two groups in median number of days with URTI symptoms or in the use of conventional medication/care. CONCLUSIONS: In this study there was no effect over placebo for self treatment with one of three self selected, ultramolecular homeopathic medicines in preventing childhood URTI. This can be due to the lack of effect of the highly diluted homeopathic medicines or the process of selection and type of medicines.     

氟哌噻吨与氟奋乃静治疗精神分裂症的随机对照试验

目的：探索氟哌噻吨治疗精神分裂症的疗效及不良反应。方法：用氟哌噻吨和氟奋乃静随机双盲对照治疗精神分裂症共５２例，每组２６例，治疗期为６ｗｋ。采用ＢＰＲＳ，ＳＡＮＳ，ＣＧＩ和ＴＥＳＳ量表评分。结果：ＢＰＲＳ总分显著下降，Ｐ值均＜０．０１，在焦虑抑郁因子分及产生显效时间方面，氟哌噻吨组优于氟奋乃静组。ＳＡＮＳ总分及因子分方面氟哌噻吨组Ｐ值均＜０．０５，氟奋乃静组无统计学意义。结论：氟哌噻吨疗效优于氟奋乃静，氟奋乃静的锥体外系不良反应较氟哌噻吨为重。     

An open study of remoxipride,a benzamide derivative,in schizophrenia

Remoxipride is a novel substituted benzamide derivative with specific dopamine-(D₂)-receptor blocking properties and selective action on brain mesolimbic functions. Ten inpatients with a DSM-III diagnosis of schizophrenia were treated with the drug in a 6-week open-label study. After 1 week placebo washout, the patients were given stepwise increased doses from 20 to 100 mg t.i.d. Most patients showed a clinically significant improvement; the mean scores in the Brief Psychiatric Rating Scale decreased from 25.8 at baseline to 11.3 at endpoint. Few adverse events were recorded and the rated extrapyramidal symptoms were lower at endpoint than at baseline. No abnormalities in clinical chemistry, haematology, cardiovascular assessments or EEG recordings were seen.     

齐拉西酮治疗精神分裂症的随机、双盲、双模拟、多中心研究

目的:评价齐拉西酮治疗精神分裂症的疗效及安全性。方法:采用随机、双盲、双模拟、平行对照、多中心研究。齐拉西酮组和氯丙嗪组各120例,分别给予齐拉西酮和氯丙嗪及与齐拉西酮和氯丙嗪外观相似的模拟药,剂量从20mg·d-1和50mg·d-1开始,wk 2～6调节至60～160 mg·d-1和250～600mg·d-1。均分2次口服,观察期为6wk,采用阳性和阴性症状量表(PANSS),简明精神病量表(BPRS)及临床总体印象量表(CGI)评价疗效。通过体检、实验室检查、心电图检查及其他不良事件的收集评价安全性。结果:全分析集(FAS)和安全集(SS)统计共238例,试验组120例,对照组118例。符合方案集(PP)205例,试验组112例,对照组93例。根据FAS人群分析,试验组的疗效不劣于对照组。2组PANSS评分及减分无差异。试验组治疗有效率为62.5％,对照组为58.5％(P>0.05)。试验组不良事件发生率为66.7％,不良反应发生率为62.5％;对照组分别为66.1％和63.6％(P>O.05),2组均未出现严重不良事件。但对照组肝功能异常发生率(5.9％)比试验组(1.7％)高,差异有统计学意义(P<0.05)。结论:齐拉西酮用于精神分裂症的治疗是有效而安全的,治疗剂量范围为60-160mg·d-1,起始治疗剂量为20mg·d-1(进餐时服)。     

阿立哌唑治疗精神分裂症的多中心随机双盲对照试验

目的:评价阿立哌唑治疗精神分裂症的疗效及安全性。方法:采用多中心随机双盲双模拟、阳性药平行对照的方法。以利司哌酮(昔名利培酮)为对照,受试者分别口服阿立哌唑10~30 mg.d-1与利司哌酮2~6 mg.d-1,疗程42 d。结果:共收集精神分裂症病人222例,其中阿立哌唑组111例与利司哌酮组111例。治疗结束时,2组PANSS总分与BPRS总分较治疗前均显著降低(P<0.01);PANSS总分减分率阿立哌唑组(65±s28)%,利司哌酮组为(67±26)%,差异无显著意义(P>0.05)。临床总有效率:阿立哌唑组为77.0%,利司哌酮组为79.2%,2组比较差异无显著意义(P>0.05)。阿立哌唑组常见的不良反应为:静坐不能、震颤、失眠、心动过速,不良反应较利司哌酮组少。结论:阿立哌唑治疗精神分裂症的疗效与利司哌酮相似,不良反应较利司哌酮为少,是一种安全而有效的抗精神病药。     

Smoking cessation and relapse prevention for postpartum women: results from a randomized controlled trial at 6, 12, 18 and 24 months

Aim

To test the efficacy of an aid to cessation/relapse prevention intervention for women postpartum.

Method

Two-armed randomized controlled trial. Follow-ups at 6, 12, 18, and 24 months, screenings on maternity wards. Intervention group received face-to-face counseling 40 days postpartum plus telephone counseling calls 4 and 12 weeks later. Control group received usual care plus self-help material for each parent.

Results

With regard to smoking cessation, 4 week point prevalence abstinent rates were higher in the treatment group at 6, 12, and 18 months (7% vs. 1%, 7% vs. 2%, and 9% vs. 1%, respectively). Sustained abstinence was higher in the treatment group at 6 months follow-up (3% vs. 0%). No difference was observed with regard to relapse prevention.

Discussion

Regarding aid to cessation we observed small effects, regarding relapse prevention no effect. In order to capitalize on the opportunity childbirth poses with regard to smoking, theories on relapse prevention in smoking cessation that guide in designing interventions are needed.     

Efficacy of loxapine in the treatment of paranoid schizophrenia

A combined analysis of data from 11 controlled studies of loxapine versus either chlorpromazine or trifluoperazine in acute schizophrenia (5 studies) and chronic schizophrenia (6 studies) showed statistically significant superiority of loxapine on several items and factors of standardized psychiatric rating scales. Upon review of these findings, it was observed that the rating scale symptoms for which loxapine appeared superior to the reference compounds could, in the main, be considered a broad paranoid cluster. The data were then reanalyzed to detect possible differences in efficacy of loxapine versus the reference compounds in those patients with a clinical diagnosis of schizophrenia, paranoid type and in those patients of any diagnostic subtype other than paranoid. Results of these analyses demonstrated clear superiority of loxapine in paranoid schizophrenic patients; nonparanoid patients responded at least equally as well to loxapine as to the reference compounds. Findings could not be attributed to inadequate dosages of the reference compounds or inequality of treatment groups at baseline.Presented in part at the Ninth Annual Congress, Collegium Internationale Neuropsychopharmacologicum, Paris, July, 1974     

思瑞康与氯氮平治疗慢性精神分裂症的对照研究

目的比较思瑞康和氯氮平治疗慢性精神分裂症的疗效及副反应。方法将67例慢性精神分裂症病人随机分成2组,思瑞康组36例,氯氮平组31例,治疗观察12周,分别于入组前,服药后4周、8周、12周用简明精神病评定量表(BPRS)、阴性症状量表(SANS)、临床疗总评量表(CGI)评定疗效,治疗中需处理不良反应症状量表(TESS)评定副反应。结果(1)思瑞康组总有效率为66.5%,氯氮平组67.7%,两组差异无统计学意义,(P>0.05)。(2)治疗后第4周、8周和12周,思瑞康组及氯氮平组的治疗前后SANS降分有显著差异(P<0.01),思瑞康组与氯氮平组治疗前后比较SANS降分无显著差异(P>0.05)。(3)TESS评定显示,思瑞康的副反应发生率低于氯氮平,且程度低。结论思瑞康和氯氮平治疗慢性精神分裂症病人均有效,思瑞康可用于不能耐受氯氮平副反应的慢性精神分裂症病人。     

Effects of remoxipride,a dopamine D-2 antagonist antipsychotic,on sleep-waking patterns and EEG activity in rats and rabbits

The antipsychotic remoxipride, a selective dopamine D-2 receptor antagonist, was studied for its effects on sleep-waking patterns in the rat and electroencephalographic (EEG) activity in the rabbit. Haloperidol, which has lesser selectivity for D-2 receptors, was used for comparison. In the rat, remoxipride (1–10 mg/kg SC) did not affect either total sleep or non-rapid eye movement (non-REM) sleep. Only REM was slightly reduced by the high dose of 10 mg/kg. Haloperidol (0.1–1 mg/kg PO) enhanced duration of both total sleep and non-REM sleep. In the rabbit, remoxipride (3 and 10 mg/kg IV) induced no significant changes of the EEG power spectrum over 0.1–38.5 Hz or individual frequency bands. In both cortex and hippocampus the drug did not alter the arousal response to acoustic sensory stimuli. Plasma concentration of remoxipride 10 mg/kg IV in rabbits declined biexponentially and was 4 and 2 µmol/1 at 30 min and 1 h, respectively. Haloperidol (0.3 and 1 mg/kg) slowed down the EEG activity, enhanced the power spectrum of the cortical and hippocampal activity, and significantly reduced the duration of arousal induced by sensory stimuli. The results indicate that, unlike haloperidol, remoxipride has weak or no sedative effects. The data also provide support to the notion that D-2 receptors are not involved in the regulation of states of sleep and sedation.     

膀胱灌注辣椒辣素类似物治疗特发性膀胱过度活动症随机对照临床研究

目的探讨膀胱灌注辣椒辣素类似物（RTX）治疗特发性膀胱过度活动症（IOAB）的临床效果。方法IOAB患者26例随机分为试验A组和对照B组。A组14例，用100nmol／LRTX 100ml灌注膀胱保留30min后排空。B组12例，用1：5000呋喃西林（安慰剂）替代RTX，方法同A组。观察A，B两组用药前、用药后1个月、用药后3个月的临床症状（每日排尿次数、尿急程度）和尿动力学参数（FDV、MCBC、Qmax）。结果治疗前与治疗后1个月、3个月的临床症状和尿动力学参数比较，A组差异有显著意义（P〈0．01），B组差异无显著意义（P〉0．05）。14／26例（54％）有轻度尿道刺激症状或膀胱区不适，均可耐受。结论RTX单剂量膀胱灌注能安全有效地改善IOAB临床症状和尿动力学指标。