Fipexide, an effective cognition activator in the elderly: a placebo-controlled, double-blind clinical trial

Forty geriatric in-patients with severe cognition disorders were randomly allocated to treatment with either 600 mg fipexide daily or placebo over a period of 3 weeks. Before and after treatment, the symptoms of cognitive performance (disorders of memory and attention, asthenia, apathy and disorders of coenaesthesia) were monitored and scored. Similarly, the Thurstone test (symbol matching test) was performed and time to completion, number of errors and exactitude index were recorded. Haemodynamics, haematology and haematochemistry investigations were made before and after treatment, and accessory symptoms of potential side-reactions were monitored by positive questioning. Treatment with fipexide was associated with a significant improvement in each and all monitored symptoms and signs to an average extent of 60%, whereas placebo was not. Similarly, the patients given fipexide experienced a significant improvement in the Thurstone test, in terms of time to completion (-22%), number of errors (-46%) and exactitude index (+60%); again, placebo was not associated with any significant improvement (variations, respectively, of -5%, -14%, and +24%). Overall, 85% of the patients given fipexide experienced clinical improvement to a greater or lesser degree, a significantly greater proportion than that associated with placebo (25%; p less than 0.001). Tolerance, both subjective and objective, was good in both treatment groups.     

Oxcarbazepine in patients with impulsive aggression: a double-blind, placebo-controlled trial

OBJECTIVE: Impulsive aggression is a common clinically significant symptom, but there are few controlled studies evaluating drug treatment. This study evaluated oxcarbazepine in patients with impulsive aggression and whether diagnosis or other baseline characteristics predict response. METHOD: Eligible outpatients had clinically significant impulsive aggression, without other psychiatric symptoms clearly requiring treatment. Patients were randomized to oxcarbazepine or placebo, double-blind, for 10 weeks, at a variable dose increasing to 1200 mg/d if tolerated and to 2400 mg/d if aggression persisted. Primary outcome measures were (1) change in a Global Overt Aggression rating derived from the Overt Aggression Scale-Modified and (2) patient-rated global improvement. RESULTS: Of 48 patients, 24 per group, 9 dropped out due to adverse events, but 45 completed at least 4 weeks on double-blind medication. Analyses showed consistent evidence of benefit from oxcarbazepine, compared with placebo, on both primary efficacy measures and most secondary measures. There were no significant interactions between diagnosis or other baseline characteristics and differential response to oxcarbazepine or placebo. CONCLUSION: Oxcarbazepine appears to benefit adults with clinically significant impulsive aggression.     

Efficacy of Echinacea purpurea in patients with a common cold. A placebo-controlled, randomised, double-blind clinical trial

Common colds are one of the most frequent acute illnesses with major economical impact. Echinaceae purpureae herba (Echinacin, EC31J0) has shown promising results in the relief of common cold symptoms and the time taken to improvement compared to placebo. This study was aimed to confirm these findings by performing a randomised, double-blind, placebo-controlled clinical trial. A total of 80 adult male or female patients with first signs of a cold were recruited. The number of days of illness with a complete picture of the common cold (defined by the modified Jackson score of at least 5 points and experience of rhinorrhea and/or a subjective sensation of having a cold) was the primary end-point. In the verum group the median time of illness was 6.0 days compared to 9.0 days in the placebo group, assigning zero time for patients without a complete picture (one-sided p = 0.0112). EC31J0 was well tolerated and clinically effective in alleviating symptoms more rapidly than placebo in patients with a common cold.     

A double-blind comparison of felodipine and hydrochlorothiazide added to metoprolol to control hypertension

Summary Seventy-six uncomplicated hypertensive patients treated in General Practice, whose seated diastolic blood pressure (Phase V) (dBP) remained 95 mmHg after a minimum of 4 weeks treatment with metoprolol 50 mg b.i.d. as antihypertensive monotherapy, were randomized to receive the selective calcium antagonist felodipine 5 mg b.i.d. or hydrochlorothiazide 12.5 mg b.i.d. in addition to metroprolol 50 mg b.i.d. The trial duration was 8 weeks, the dose of the felodipine or hydrochlorothiazide being doubled after 4 weeks if control of BP (dBP <90 mmHg) was not achieved on the initial doses.Over the trial period of 8 weeks, felodipine reduced dBP from 102 to 85 mmHg and hydrochlorothiazide from 101 to 91 mmHg; the dBP reduction in the felodipine group was greater than that in the hydrochlorothiazide group (17 vs 9 mmHg) and the attained dBP lower in the felodipine group. About half of the patients in each group required the higher dose.Both regimes were effective and well tolerated. In the dosages used, felodipine was a slightly more effective antihypertensive drug than hydrochlorothiazide when added to metoprolol. There was no apparent difference in the tolerability of the two regimes.     

Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized,double-blind,placebo-controlled trial

Abstract

Objective:

Type 2 diabetes in the elderly is an important and insufficiently studied public health problem. This study evaluated sitagliptin monotherapy in patients with type 2 diabetes aged ≥65 years.     

Doxazosin in combination with atenolol in essential hypertension: a double-blind placebo-controlled multicentre trial

Doxazosin (mean dose 11 mg) given once daily in combination with 100 mg atenolol (n = 44) was compared with placebo and atenolol (n = 43) in a double-blind, multicenter study in patients with mild to moderate essential hypertension. In the atenolol/doxazosin-treated group, standing blood pressure significantly decreased by 17.0/12.3 mm Hg compared to 6.2/6.7 mm Hg in the atenolol/placebo group whereas supine blood pressure decreased by 13.2/9.8 mm Hg and 9.2/6.0 mm Hg, respectively in the two groups. Serum lipids did not change significantly in either group. The majority of side-effects reported were mild and transient. This study confirms that doxazosin may be safely combined with a beta-blocker. Doxazosin proved to be well tolerated and effective in patients with blood pressure refractory to atenolol alone.     

Topiramate add-on treatment in schizophrenia: a randomised, double-blind, placebo-controlled clinical trial

Glutamate antagonists such as topiramate have been proposed based on the glutamate hypothesis of schizophrenia because its properties encourage its exploration and possible development as a medication for the treatment of schizophrenia. A randomised, double-blind, placebo-controlled clinical trial was performed on 18- to 45-year-old patients with schizophrenia. Baseline information including vital signs, height, weight, smoking status, demographic characteristics, (past) psychiatric history, medication history and medication-related adverse effects were collected. Patients were randomly assigned to a topiramate or placebo group. Efficacy of medication was measured by administering Positive and Negative Syndrome Scale (PANSS), and tolerability of treatment was recorded on day 0 (baseline), day 28 and day 56. PANSS values (95% confidence interval) at baseline, day 28 and day 56 in the topiramate group were 96.87 (85.37-108.37), 85.68 (74.67-96.70) and 76.87 (66.06-87.69), respectively; compared with 101.87 (90.37-113.37), 100.31 (89.29-111.32) and 100.56 (89.74-111.37) in the placebo group. General linear model for repeated measures analysis showed that topiramate has lowered PANSS values significantly compared with the placebo group. Similar significant decline patterns were found in all three subscales (negative, positive and psychopathology sign). Clinical response (more than 20% reduction in PANSS) was significantly higher in topiramate-treated subjects than controls (50% vs 12.5%). Topiramate can be an effective medication in controlling schizophrenic symptoms, considering its effect on negative symptoms and controlling antipsychotic-associated weight gain.     

来氟米特治疗强直性脊柱炎的随机双盲安慰剂对照临床试验

目的探讨来氟米特治疗强直性脊柱炎(AS)的疗效和安全性。方法用随机、双盲、安慰剂对照的临床研究方法,将60例(其中29例伴周围关节炎)经柳氮磺吡啶和非甾体抗炎药治疗无效的活动性AS患者按2∶1的比例随机分为试验组(40例)和对照组(20例),分别口服来氟米特20 mg,qd和安慰剂,疗程12 wk,观察疗效和不良反应。结果治疗12 wk时试验组ASAS20有效率为39%,显著高于对照组(5%,P<0.01)。试验组中有周围关节炎AS与无周围关节炎AS比较,C反应蛋白、压痛周围关节数、肿胀周围关节数、Bath强直性脊柱炎患者整体评分、Bath强直性脊柱炎功能指数、Bath强直性脊柱炎疾病活动指数、医生和患者对疾病活动性的整体评价等指标有显著改善(均P<0.05),显著提高ASAS20有效率(P<0.05)。不良反应发生率在试验组与对照组间无显著差异(P>0.05)。结论来氟米特治疗伴有周围关节炎的AS安全有效。     

A randomized, double-blind, placebo-controlled trial of fluvoxamine in patients with schizophrenia: a preliminary study

ABSTRACT: Cognitive impairments in schizophrenia are associated with suboptimal psychosocial performance. Several lines of evidence have suggested that endoplasmic reticulum protein sigma-1 receptors were involved in cognitive impairments in patients with schizophrenia and that the sigma-1 receptor agonist fluvoxamine was effective in treating cognitive impairments in animal models of schizophrenia and in some patients with schizophrenia. A randomized, double-blind, placebo-controlled, parallel trial of fluvoxamine adjunctive therapy in patients with schizophrenia was performed. A total of 48 patients with chronic schizophrenia were enrolled. Subjects were randomly assigned to an 8-week administration of add-on fluvoxamine (n = 24, titrated up to 150 mg/d) or placebo (n =24) in a total 12-week double-blind trial. The primary outcome measure was the Cambridge Neuropsychological Test Automated Battery (CANTAB), assessing visual memory, working memory, attention, and executive function. The secondary outcome measures were the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Quality of Life Scale, and the Montgomery-?sberg Depression Rating Scale. Fluvoxamine was well tolerated. No significant time × group interaction effects were observed in the scores of the CANTAB, Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, or the Montgomery-?sberg Depression Rating Scale. However, in secondary analyses, the change from baseline to end point on the Spatial Working Memory strategy score (executive function) of CANTAB improved in the fluvoxamine group. This study suggests no major benefit of fluvoxamine adjunctive therapy to improve cognitive impairments in patients with schizophrenia. Nevertheless, a further study using a large sample size will be needed to confirm the secondary analyses findings.     

Nefazodone treatment of major depression in alcohol-dependent patients: a double-blind, placebo-controlled trial

Depression is the most common comorbid psychiatric illness in patients with alcohol dependence. This double-blind study tested the efficacy of nefazodone versus placebo for the treatment of depression in actively drinking alcohol-dependent patients who were also participating in weekly group treatment for alcoholism. Sixty-four subjects with major depression disorder and alcohol dependence with a history of at least one prior episode of depression when not drinking were randomly assigned to receive 12 weeks of either nefazodone or placebo and participated in a weekly psychoeducational group on alcoholism. Subjects were assessed every 2 weeks for depression, anxiety, side effects, and drinking frequency. Subjects taking nefazodone were significantly more likely to complete the study (62%) than those taking placebo (34%). Analyses of covariance using drinks per week as a time-dependent covariate showed lower Hamilton Rating Scale for Depression scores at week 8 for end-point analysis and at weeks 8 and 12 for completers. The endpoint analysis demonstrated a significantly greater response in the nefazodone group (48%) than in the placebo group (16%). Both groups showed a similarly significant decrease in the average number of alcoholic drinks consumed per day over the course of the study. Although the number of adverse effects was significantly greater for the nefazodone group, there were no severe adverse events, and nefazodone was well tolerated. Nefazodone is a safe and effective antidepressant to use in a population of alcohol-dependent patients with depression who have a high degree of comorbidity. Nefazodone treatment was superior to placebo in alleviating depression in these patients but did not add any advantage over the psychoeducational group in terms of drinking outcomes.     

Pindolol augmentation in patients with treatment-resistant panic disorder: A double-blind, placebo-controlled trial

The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder (PD). Twenty-five outpatients having PD with or without agoraphobia were included. These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day. Treatment-resistant PD was defined as a less than 20% reduction in score on the Panic Self-Questionnaire (number of attacks per week) (PSQ) and the Clinical Anxiety Scale With Panic Attacks (CAS+PA). These patients continued to receive fluoxetine 20 mg/day and were randomly assigned to additionally receive either pindolol (2.5 mg three times daily) or placebo for the following 4 weeks. Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale for Depression (HAM-D), the CAS+PA, the NIMH Anxiety Scale, the PSQ, and the Clinical Global Impression Scale. The data were analyzed using a repeated-measures analysis of variance (ANOVA) and a t-test for independent samples. Patients treated with the combination of pindolol and fluoxetine (N = 13) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales, with the exception of HAM-D. The statistical differences were shown using the repeated-measures ANOVA (baseline, week 2, week 4) and also with t-tests from the second week of the trial. These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD.     

Nifedipine monotherapy in the hypertensive elderly: a placebo-controlled clinical trial

A single-blind, placebo-controlled study was carried out to evaluate the suitability of slow-release nifedipine as antihypertensive monotherapy for the elderly. After a wash-out period, nifedipine slow-release tablets (20 mg twice daily) followed by matching placebo were administered, each for 4 weeks, to 23 patients over 60 years of age with essential mild to moderate hypertension. Nifedipine significantly reduced the systolic and diastolic blood pressure, and increased the pulse rate in both supine and upright positions. The pre-treatment supine systolic blood pressure proved the best single predictor of the blood pressure decreases in both positions. The decrease in mean arterial blood pressure correlated significantly with the nifedipine plasma concentration. Significant biochemical changes were observed with nifedipine, namely increased serum K+ level and decreased levels of serum Na+, cholesterol and triglycerides. Side-effects in general were mild and transient; nevertheless, 3 patients dropped out because of severe leg oedema.     

非洛地平联合美托洛尔治疗65例高血压患者临床分析

目的探讨非洛地平联合美托洛尔治疗高血压的临床疗效及安全性。方法将笔者所在医院2009年6月～2011年5月诊治的高血压患者130例,随机分为观察组和对照组各65例,观察组采用非洛地平联合美托洛尔治疗,对照组单纯用美托洛尔治疗。比较分析两组的临床疗效。结果观察组的临床治疗总有效率显著高于对照组,差异有统计学意义(P<0.05);两组患者服药期间不良反应比较,差异无统计学意义(P>0.05)。结论非洛地平联合美托洛尔治疗高血压疗效显著,安全性高,值得进行临床推广。     

The efficacy and safety of eperisone in patients with cervical spondylosis: results of a randomized, double-blind, placebo-controlled trial.

A randomized, double-blind, clinical trial was undertaken to assess the activity of eperisone hydrochloride (50 mg t.i.d.), a commonly used muscle relaxant, as a treatment for cervical spondylosis in 157 patients. The results showed a clear benefit of eperisone treatment with regard to pain in the nuchal region, back pain, pain in arms and shoulders, stiffness and other symptoms of cervical spondylosis, while the tolerability of the treatment was optimal.     

Effects of intravenous high dose co-dergocrine mesylate ('Hydergine') in elderly patients with severe multi-infarct dementia: a double-blind, placebo-controlled trial

A double-blind, placebo-controlled trial was carried out in 40 patients affected by multi-infarct dementia to see if a daily intravenous infusion of 3 mg co-dergocrine mesylate ('Hydergine') over 14 days would improve severely deteriorated elderly patients and shorten the latent period (3 months) which is observed when the drug is given orally. All the patients had severe mental impairment, psychological deficit or altered consciousness. A Hachinski score of 7 or more, and a cumulative score of at least 12 points on SCAG scale Items 1, 2 and 4 (anxiety/depression) and/or Items 5, 6 and 8 (alertness/confusion) were required for admission. After 1 week of intravenous infusion of placebo, patients were randomly allocated to treatment with co-dergocrine mesylate or placebo, from Day 1 to Day 14. The solutions were infused over a period of 2 hours. During the follow-up period from Day 15 to Day 21, the patients did not receive any treatment. Thirty-six patients (17 on co-dergocrine mesylate, 19 on placebo) completed the study. The results, as rated on the SCAG scale, indicated significant improvements, in favour of co-dergocrine mesylate, in cognitive dysfunction, mood depression, withdrawal and overall impression. Furthermore, the factor fatigue on the Nowlis scale and clinical global assessments by physicians also showed significant advantages of the co-dergocrine mesylate group over placebo. Nine out of 17 co-dergocrine mesylate patients complained of side-effects, usually experienced during infusion; they consisted mainly of nausea (6 patients), gastric discomfort (2 patients), and tremor, nasal congestion, flushing, hypotension and hypertension (1 patient each). Despite the appearance of side-effects, general tolerability was rated as 'good' by both physicians and patients. It is concluded, therefore, that intravenous high dose co-dergocrine mesylate treatment has a fast and clinically relevant effect on the key clinical symptoms of multi-infarct dementia.     

Twenty-four-hour blood pressure monitoring during treatment with extended-release felodipine versus slow-release nifedipine in elderly patients with mild to moderate hypertension: a randomized, double-blind, cross-over study

Objective: In a multicentre, double-blind, parallel group study, the anti-anginal and the anti-ischaemic efficacy of 12 weeks of therapy with the vasodilating β-adrenoceptor-blocker carvedilol 25 mg b.i.d. was compared with verapamil 120 mg t.i.d. Methods: During a 2-week placebo run-in period, patients were required to have two treadmill exercise tests (modified Bruce Protocol) differing by not more than 15% with regard to total exercise time (TET). Of 313 patients enrolled, 248 were randomized and 212 completed the study according to the protocol. Results: The primary variable TET was analysed using the Cox Proportional Hazards Model to take into account censored values due to the patient stopping the exercise test for reasons other than angina. Forty-three per cent of patients allocated to carvedilol and 36% to verapamil did not stop with angina at the final visit. There was no difference in the TET between the groups, the risk ratio being 1.14 in favour of carvedilol (90% CI 0.85–1.52). TET increased from 378 s at baseline to 436 s at the final visit in the carvedilol group and from 386 to 438 s in the verapamil group. Results for time to angina and time to 1 mm ST-segment depression were similar. Compared to verapamil, carvedilol significantly reduced HR, systolic BP and rate pressure product at peak exercise. Analysis of 48 h Holter monitor data showed a greater reduction of HR and PVCs with carvedilol. Lown grading improved in both groups. Adverse events were reported by 48% (3.2% serious adverse events) of patients taking carvedilol and 58% (5.7% serious adverse events) taking verapamil. Conclusion: Carvedilol is at least as effective as verapamil in the management of chronic stable angina and demonstrated a favourable adverse event profile. Received: 12 August 1996 / Accepted in revised form: 2 December 1996     

Nicotine gum in smoking cessation: a placebo-controlled, double-blind trial

Sixty subjects were run in a study comparing the use of nicotine gum with placebo gum during cessation from smoking. Subjects were given clinic support and chewed the gum ad libitum. A survival analysis showed the two groups differed significantly in successful abstinence over time (p less than .03). Differences between groups appeared early (within weeks) and, at six months, a 28% superiority of nicotine over placebo gum was demonstrated with mean success rates of 48% and 20%, respectively. Between six months and one year, relapse in the nicotine group accounted for the 30% vs. 20% success rates for nicotine and placebo observed at one year. In a pilot study ("dispensary") testing the efficacy of the two gums when intervention was minimal, subjects in both groups resumed smoking within the first two weeks. The enhanced short-term success rates with nicotine gum in the clinic study are attributed to an effective interaction between use of the active preparation and clinic support. Long-term cessation may require extended maintenance procedures and/or an identification of optimal gum use.