Showing papers on "Placebo published in 1994"

Cyclosporine in Severe Ulcerative Colitis Refractory to Steroid Therapy

Abstract: Background There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced almost 40 years ago. In an uncontrolled study, 80 percent of 32 patients with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy. Methods We conducted a randomized, double-blind, controlled trial in which cyclosporine (4 mg per kilogram of body weight per day) or placebo was administered by continuous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least seven days of intravenous corticosteroid therapy. A response to therapy was defined as an improvement in a numerical symptom score (0 indicated no symptoms, and 21 severe symptoms) leading to discharge from the hospital and treatment with oral medications. Failure to respond to therapy resulted in colectomy, but some patients in the placebo group who had no response and no urgent need for surgery were subseque...

Risperidone in the treatment of schizophrenia.

Abstract: Objective: The purpose ofthis study was to investigate the safety and efficacy of risperidone in the treatment ofschizophrenic patients and determine its optimal dose Method: This double-blind study included 388 schizophrenic patients drawn from 20 sites in the United States Patients were randomly assigned to 8 weeks’ treatment with placebo, one of four doses of risperidone (2, 6, 1 0, or 1 6 mg), or 20 mg ofhaloperidol daily Results: Clinical improvement (20% reduction in totalscores on the Positive and Negative Syndrome Scale for Schizophrenia) at the study end point was shown by 35% ofthe patients receiving 2 mg ofrisperidone, 57% receiving 6 mg, 40% receiving 1 0 mg, and 51 % receiving 1 6 mg; and by 30% receiving haloperidoland 22% receiving placebo Statistically significant differences in clinical improvement were found between 6 and 1 6 mg of risperidone versus placebo and versus haloperidol Positive symptom scores were significantly lower after 6, 10, and 1 6 mg of risperidone and 20 mg ofhaloperidol than placebo; negative symptom scores, however, were reduced significantly, compared with placebo, only after 6 and 1 6 mg ofrisperidone The incidence of extrapyramidal side effects (measured by the Extrapyramidal Symptom Rating Scale) was significantly higher in patients treated with 1 6 mg of risperidone or 20 mg of haloperidol than placebo The results indicate that the optimal daily dose ofrisperidone for most schizophrenic patients in this study was 6 mg; this dose was as effective as 1 6 mg, and the incidence of extrapyramidal symptoms in patients receiving 6 mg of risperidone was no higher than that in patients receiving placebo Conclusions: Risperidone is a safe antipsychotic that is effective against both the positive and negative symptoms of schizophrenia (AmJ Psychiatry 1994; 151:825-835)

Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group.

Abstract: Objective. —To further define the safety and efficacy of recombinant human interleukin 1 receptor antagonist (rhIL-1ra) in the treatment of sepsis syndrome. Study Design. —Randomized, double-blind, placebo-controlled, multicenter, multinational clinical trial. Population. —A total of 893 patients with sepsis syndrome received an intravenous loading dose of rhIL-1ra, 100 mg, or placebo followed by a continuous 72-hour intravenous infusion of rhIL-1ra (1.0 or 2.0 mg/kg per hour) or placebo. Outcome Measure. —Twenty-eight—day all-cause mortality. Results. —There was not a significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication (n=893; generalized Wilcoxon statistic, P =.22) or among patients with shock at study entry (n=713; generalized Wilcoxon statistic, P =.23), the two primary efficacy analyses specified a priori for this trial. Results from secondary analyses suggest an increase in survival time with rhIL-1ra treatment among patients with dysfunction of one or more organs (n=563; linear dose-response, P =.009). Retrospective analysis demonstrated an increase in survival time with rhIL-1ra treatment among patients with a predicted risk of mortality of 24% or greater (n=580; linear dose-response, P =.005) as well as among patients with both dysfunction of one or more organs and a predicted risk of mortality of 24% or greater (n=411; linear dose-response, P =.002). Conclusions. —There was not a statistically significant increase in survivial time for rhIL-1ra treatment compared with placebo among all patients who received the study medication or among patients with shock at study entry. Secondary and retrospective analyses of efficacy suggest that treatment with rhIL-1ra results in a dose-related increase in survival time among patients with sepsis who have organ dysfunction and/or a predicted risk of mortality of 24% or greater. ( JAMA . 1994;271:1836-1843)

A randomized trial of beta-blockade in heart failure. The Cardiac Insufficiency Bisoprolol Study (CIBIS). CIBIS Investigators and Committees.

Abstract: BACKGROUND Functional benefit in heart failure due to idiopathic dilated cardiomyopathy has been observed after beta-blockade, but improvement in survival has not been established in a large-scale randomized trial. This was the main objective of the Cardiac Insufficiency Bisoprolol Study (CIBIS). METHODS AND RESULTS Six hundred forty-one patients with chronic heart failure of various etiologies and a left ventricular ejection fraction of < 40% entered this placebo-controlled, randomized, double-blind study. Patients were in New York Heart Association functional class III (95%) or IV (5%) at inclusion. All received background diuretic and vasodilator therapy (an angiotensin-converting enzyme inhibitor in 90% of cases). A total of 320 patients was randomized to bisoprolol and 321 to placebo. Mean follow-up was 1.9 years. Bisoprolol was well tolerated without between group difference in premature treatment withdrawals (82 on placebo, 75 on bisoprolol; NS). The observed difference in mortality between groups did not reach statistical significance: 67 patients died on placebo, 53 on bisoprolol (P = .22; relative risk, 0.80; 95% confidence interval, 0.56 to 1.15). No significant difference was observed in sudden death rate (17 on placebo, 15 on bisoprolol) or death related to documented ventricular tachycardia or fibrillation (7 on placebo, 4 on bisoprolol). Bisoprolol significantly improved the functional status of the patients; fewer patients in the bisoprolol group required hospitalization for cardiac decompensation (90 on placebo versus 61 on bisoprolol, P < .01), and more patients improved by at least one New York Heart Association functional class (48 on placebo versus 68 on bisoprolol, P = .04) by the end of follow-up period. CONCLUSIONS These results confirm previous trials evidence that a progressively increasing dose of beta-blocker in severe heart failure confers functional benefit. Subgroup analysis suggested that benefit from beta-blockade therapy was greater for those with nonischemic cardiomyopathy. However, improvement in survival while on beta-blockade remains to be demonstrated.

A 30-Week Randomized Controlled Trial of High-Dose Tacrine in Patients With Alzheimer's Disease

Abstract: Objective. —To evaluate the efficacy and safety of high-dose tacrine hydrochloride over 30 weeks in patients with probable Alzheimer's disease. Design. —A 30-week randomized, double-blind, placebo-controlled, parallel-group trial. Setting. —Outpatients at 33 US centers. Patients. —Men and women at least 50 years of age with mild to moderate Alzheimer's disease and otherwise in good health. Interventions. —Group 1 received placebo; group 2 received 40 mg/d of tacrine for 6 weeks, then 80 mg/d for 24 weeks; groups 3 and 4 received 40 mg/d of tacrine for 6 weeks, 80 mg/d for 6 weeks, and 120 mg/d for 6 weeks. Group 3 remained on a dosage of 120 mg/d for a total of 18 weeks; after 6 weeks at 120 mg/d, group 4 titrated to 160 mg/d for the last 12 weeks. Primary Outcome Measures. —Clinician Interview-Based Impression (CIBI), Alzheimer's Disease Assessment Scale—Cognitive subscale (ADAS-Cog), and Final Comprehensive Consensus Assessment (FCCA). Results. —A total of 663 patients entered the study; 653 patients were included in an intent-to-treat (ITT) analysis; 263 had evaluable data at 30 weeks. The results of the ITT analysis revealed significant (P≤.05) dose-response trends and between-group comparisons on CIBI and ADAS-Cog. In evaluable patients, significant dose-response trends were observed for all three primary measures (P≤.001). Significant differences in favor of 160 mg/d of tacrine vs placebo were observed on the CIBI (P≤.002) and ADAS-Cog and FCCA (P≤.001), as well as caregiver-global and quality-of-life assessments (P≤.05). On the CIBI, 23% and 42% of tacrine-treated patients in the ITT and evaluable-patient populations, respectively, were rated improved compared with 17% and 18% of placebo patients, respectively. The primary reasons for withdrawal of tacrine-treated patients were asymptomatic liver transaminase elevations (28%) and gastrointestinal complaints (16%). These adverse events were reversible on discontinuation of treatment, and many patients were able to restart tacrine. Conclusions. —Tacrine produced statistically significant, dose-related improvements on objective performance-based tests, clinician- and caregiver-rated global evaluations, and measures of quality of life. There was no evidence that the large number of patient withdrawals biased the overall conclusions of the study. (JAMA. 1994;271:985-991)

A Randomized Placebo-Controlled Trial of Saccharomyces boulardii in Combination With Standard Antibiotics for Clostridium difficile Disease

Abstract: Objective. —To determine the safety and efficacy of a new combination treatment for patients with Clostridium difficile —associated disease (CDD). The treatment combines the yeast Saccharomyces boulardii with an antibiotic (vancomycin hydrochloride or metronidazole). Design. —A double-blind, randomized, placebo-controlled, parallel-group intervention study in patients with active CDD. Patients received standard antibiotics and S boulardii or placebo for 4 weeks, and were followed up for an additional 4 weeks after therapy. Effectiveness was determined by comparing the recurrence of CDD in the two groups using multivariate analysis to control for other risk factors for CDD. Setting. —National referral study of ambulatory or hospitalized patients from three main study coordinating centers. Patients. —A total of 124 eligible consenting adult patients, including 64 who were enrolled with an initial episode of CDD, and 60 who had a history of at least one prior CDD episode. Patients who were immunosuppressed due to acquired immunodeficiency syndrome or cancer chemotherapy within 3 months were not eligible. Intervention. —Treatment with oral S boulardii (1 g/d for 4 weeks) or placebo in combination with a standard antibiotic. Main Outcome Measure. —Recurrence of active CDD. Results. —A history of CDD episodes dramatically increased the likelihood of further recurrences. Multivariate analysis revealed that patients treated with S boulardii and standard antibiotics had a significantly lower relative risk (RR) of CDD recurrence (RR, 0.43; 95% confidence interval, 0.20 to 0.97) compared with placebo and standard antibiotics. The efficacy of S boulardii was significant (recurrence rate 34.6%, compared with 64.7% on placebo; P =.04) in patients with recurrent CDD, but not in patients with initial CDD (recurrence rate 19.3% compared with 24.2% on placebo; P =.86). There were no serious adverse reactions associated with S boulardii . Conclusions. —The combination of standard antibiotics and S boulardii was shown to be an effective and safe therapy for these patients with recurrent CDD; no benefit of S boulardii was demonstrated for those with an initial episode of CDD. ( JAMA . 1994;271:1913-1918)

Efficacy of Divalproex vs Lithium and Placebo in the Treatment of Mania

Abstract: Objective. —To compare the effectiveness of divalproex sodium with that of lithium and placebo in patients with acute mania. Design. —Randomized, double-blind, parallel-group study of treatment outcomes in patients with manic-depressive illness. Patients. —A total of 179 hospitalized, acutely manic patients meeting the Research Diagnostic Criteria for manic disorder, approximately half of whom had been nonresponsive to lithium previously, were studied at nine university-affiliated hospitals. Interventions. —After a minimum 3-day washout period, random assignment for 21 days to divalproex, lithium, or placebo in a 2:1:2 ratio. Dosage of divalproex and lithium was increased if tolerated to a target concentration of 1041 μmol/L (150 μg/ mL) or 1.5 mmol/L (conventionally expressed as milliequivalents per liter), respectively. Main Outcome Measures. —Primary outcome measures were changes in the Mania Rating scale derived from the Schedule for Affective Disorders and Schizophrenia. Results. —Intent-to-treat analysis for efficacy was based on data from 68, 35, and 73 patients in the divalproex, lithium, and placebo groups, respectively. Groups were initially comparable except that all eight patients with four or more manic episodes in the previous year were in the divalproex group. In 30%, 33%, and 51% of the above groups, treatment was prematurely terminated due to lack of efficacy, with fewer premature terminations from divalproex than placebo (P=.017). The proportions of patients improving at least 50% were higher for divalproex and lithium groups than for the placebo group: 48% for divalproex (P=.004) and 49% for lithium (P=.025) vs 25% for placebo. Divalproex was as effective in rapid-cycling manic patients as in other patients. Conclusions. —Both divalproex and lithium were significantly more effective than placebo in reducing the symptoms of acute mania. The efficacy of divalproex appears to be independent of prior responsiveness to lithium. (JAMA. 1994;271:918-924)

The Efficacy of Influenza Vaccination in Elderly Individuals: A Randomized Double-blind Placebo-Controlled Trial

Abstract: Objective. —To determine the efficacy of influenza vaccination in elderly people. Design. —Randomized double-blind placebo-controlled trial. Setting. —Fifteen family practices in the Netherlands during influenza season 1991-1992. Participants. —A total of 1838 subjects aged 60 years or older, not known as belonging to those high-risk groups in which vaccination was previously given. Intervention. —Purified split-virion vaccine containing A/Singapore/6/86(H1N1), A/Beijing/353/89(H3N2), B/Beijing/1/87, and B/Panama/45/90 (n=927) or intramuscular placebo containing physiological saline solution (n=911). Main Outcome Measures. —Patients presenting with influenzalike illness up to 5 months after vaccination; self-reported influenza in postal questionnaires 10 weeks and 5 months after vaccination; serological influenza (fourfold increase of antibody titer between 3 weeks and 5 months after vaccination). Results. —The incidence of serological influenza was 4% in the vaccine group and 9% in the placebo group (relative risk [RR], 0.50; 95% confidence interval [CI], 0.35 to 0.61). The incidences of clinical influenza were 2% and 3%, respectively (RR, 0.53; 95% CI, 0.39 to 0.73). The effect was strongest for the combination of serological and clinical influenza (RR, 0.42; 95% CI, 0.23 to 0.74). The effect was less pronounced for self-reported influenza. Conclusion. —In the elderly, influenza vaccination may halve the incidence of serological and clinical influenza (in periods of antigenic drift). (JAMA. 1994;272:1661-1665)

The importance of placebo effects in pain treatment and research.

Abstract: Objective. —To estimate the importance and implications of placebo effects in pain treatment and research from the existing literature, with emphasis on their magnitude and duration, the conditions influencing them, and proposed explanations. Data Sources. —English-language articles and books identified through MEDLINE (1980 through 1993) and PsycLIT (1967 through 1993) database searching, bibliography review, and expert consultation. Study Selection. —Articles were included if they pertained to the review objectives. Results. —Placebo response rates vary greatly and are frequently much higher than the often-cited one third. Placebos have time-effect curves, and peak, cumulative, and carryover effects similar to those of active medications. As with medication, surgery can produce substantial placebo effects, and this possibility is commonly overlooked in case series reports on back surgery. Individuals are not consistent in their placebo responses, and a placebo-responder personality has not been identified. Models advanced to explain placebo effects emphasize the role of anxiety, expectations, and learning. Conclusions. —Placebo effects influence patient outcomes after any treatment, including surgery, that the clinician and patient believe is effective. Placebo effects plus disease natural history and regression to the mean can result in high rates of good outcomes, which may be misattributed to specific treatment effects. The true causes of improvements in pain after treatment remain unknown in the absence of independently evaluated randomized controlled trials. ( JAMA . 1994;271:1609-1614)

Haloperidol Addition in Fluvoxamine-Refractory Obsessive-Compulsive Disorder: A Double-blind, Placebo-Controlled Study in Patients With and Without Tics

Abstract: Background: To determine the efficacy of adding haloperidol to the treatment of patients with obsessive-compulsive disorder (OCD), with or without a comorbid chronic tic disorder, who were refractory to adequate treatment with the serotonin-uptake inhibitor fluvoxamine alone. It was hypothesized that OCD patients with a concurrent chronic tic disorder would preferentially respond to this treatment. Methods: Sixty-two patients with a primary DSM-III-R diagnosis of OCD received placebo fluvoxamine for 1 week, followed by 8 weeks of active fluvoxamine. Thirty-four of these patients were refractory to fluvoxamine and were randomized in a double-blind fashion to 4 weeks of treatment with either haloperidol (n=17) or placebo (n=17) added to ongoing fluvoxamine treatment. The placebo-treated group included five women and 12 men, six inpatients and 11 outpatients, and eight patients with a comorbid chronic tic disorder. The haloperidol-treated group consisted of two women and 15 men, three inpatients and 14 outpatients, and seven patients with a comorbid chronic tic disorder. All 34 patients completed the entire study. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression scale were the principal measures of treatment outcome. Results: Haloperidol addition was significantly better than placebo in reducing the severity of obsessive-complusive symptoms as measured by the Y-BOCS. Eleven of 17 patients responded to the haloperidol, compared with none of 17 patients given placebo. Eight of eight patients with comorbid chronic tic disorders, such as Tourette's disorder, responded to double-blind haloperidol addition to ongoing fluvoxamine treatment. Haloperidol addition was of little benefit in treating OCD patients without tics. Fluvoxamine blood levels were not related to treatment response. Conclusions: The results of this study suggest that OCD patients with a comorbid chronic tic disorder constitute a clinically meaningful subtype of OCD that might require conjoint serotonin-uptake inhibitor/neuroleptic therapy for effective symptom reduction.

Imipramine in Patients with Chest Pain Despite Normal Coronary Angiograms

Abstract: Background Ten to 30 percent of patients undergoing cardiac catheterization because of chest pain are found to have normal coronary angiograms. Because these patients may have a visceral pain syndrome unrelated to myocardial ischemia, we investigated whether drugs that are useful in chronic pain syndromes might also be beneficial in such patients. Methods Sixty consecutive patients underwent cardiac, esophageal, psychiatric, and pain-sensitivity testing and then participated in a randomized, double-blind, placebo-controlled three-week trial of clonidine at a dose of 0.1 mg twice daily (20 patients), imipramine at a dose of 50 mg nightly with a morning placebo (20 patients), or placebo twice daily (20 patients); this treatment phase was compared with an identical period of twice-daily placebo for all patients (placebo phase). Results Thirteen (22 percent) of the 60 patients had ischemic-appearing electrocardiographic responses to exercise, 22 of the 54 tested (41 percent) had abnormal esophageal motility, ...

Treatment of septic shock with human monoclonal antibody HA-1A. A randomized, double-blind, placebo-controlled trial. CHESS Trial Study Group

Abstract: Objective To compare the effectiveness of 100 mg of HA-1A and placebo in reducing the 14-day all-cause mortality rate in patients with septic shock and gram-negative bacteremia in the Centocor: HA-1A Efficacy in Septic Shock (CHESS) trial, and to assess the safety of 100 mg of HA-1A given to patients with septic shock who did not have gram-negative bacteremia. Design Large, simple, group-sequential, randomized, double-blind, multicenter, placebo-controlled trial. Setting 603 investigators at 513 community and university-affiliated hospitals in the United States. Patients Within 6 hours before enrollment, the patients had been in shock with a systolic blood pressure of less than 90 mm Hg after adequate fluid challenge or had received vasopressors to maintain blood pressure. These episodes of shock began within 24 hours of enrollment. A presumptive clinical diagnosis of gram-negative infection as the cause of the shock episode and a commitment from the patients' physicians to provide full supportive care were required. Measurements Blood cultures were obtained within 48 hours of enrollment, and death at day 14 after treatment was recorded. Adverse events occurring within 14 days after enrollment were also tabulated. Results 2199 patients were enrolled; 621 (28.2%) met all enrollment criteria, received HA-1A or placebo, and had confirmed gram-negative bacteremia. Mortality rates in this group were as follows: placebo, 32% (95 and HA-1A, 33% (109 of 328) (P = 0.864, Fisher exact test, two-tailed; 95% CI for the difference, -6.2% to 8.6%). Mortality rates in the patients without gram-negative bacteremia were as follows: placebo, 37% (292 of 793) and HA-1A, 41% (318 of 785) (P = 0.073, Fisher exact test, one-tailed; CI, -0.8% to 8.8%). Conclusions In this trial, HA-1A was not effective in reducing the 14-day mortality rate in patients with gram-negative bacteremia and septic shock. These data do not support using septic shock as an indication for HA-1A treatment. If HA-1A is effective in reducing the mortality rate in patients dying from endotoxemia, these patients must be identified using other treatment criteria.

A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group.

Abstract: Background The n-3 fatty acids in fish oil affect eicosanoid and cytokine production and therefore have the potential to alter renal hemodynamics and inflammation. The effects of fish oil could prevent immunologic renal injury in patients with IgA nephropathy. Methods In a multicenter, placebo-controlled, randomized trial we tested the efficacy of fish oil in patients with IgA nephropathy who had persistent proteinuria. The daily dose of fish oil was 12 g; the placebo was a similar dose of olive oil. Serum creatinine concentrations, elevated in 68 percent of the patients at base line, and creatinine clearance were measured for two years. The primary end point was an increase of 50 percent or more in the serum creatinine concentration at the end of the study. Results Fifty-five patients were assigned to receive fish oil, and 51 to receive placebo. According to Kaplan-Meier estimation, 3 patients (6 percent) in the fish-oil group and 14 (33 percent) in the placebo group had increases of 50 percent or more i...

Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma

Abstract: The efficacy of 6 wk of therapy with oral ICI 204,219, a selective leukotriene D4 (LTD4) receptor antagonist, was evaluated in subjects with moderate asthma during a multicenter, double-blind, randomized, placebo-controlled, dose-ranging study. Subjects who entered the trial had been chronically treated for asthma with beta agonist alone or in combination with theophylline. Subjects were randomized to treatment with twice daily doses of ICI 204,219 (5, 10, or 20 mg) or placebo if they had an FEV1 between 40 and 75% of predicted values without bronchodilator therapy and a daytime asthma score > 10 (range 0 to 21 per wk) for 7 consecutive d. Efficacy was evaluated from the results of symptom assessments, pulmonary function tests, and rescue medication use. Of 276 subjects randomized to treatment, 266 (10 mg, n = 66; 20 mg, n = 67; 40 mg, n = 67; placebo, n = 66) were analyzed for efficacy. Diary card assessments showed that treatment with increasing doses of ICI 204,219 linearly improved five efficacy crite...

Psychotherapy and Pharmacotherapy for Ambulatory Cocaine Abusers

Abstract: Background: At present, there is no consensus regarding effective treatment for cocaine abuse or the most productive roles for the two major forms of treatment, pharmacotherapy and psychotherapy. We conducted the first randomized clinical trial evaluating psychotherapy and pharmacotherapy, alone and in combination, as treatment for ambulatory cocaine abusers. Methods: One hundred thirty-nine subjects were assigned to one of four conditions offered over a 12-week abstinence initiation trial: relapse prevention plus desipramine hydrochloride, clinical management plus desipramine, relapse prevention plus placebo, and clinical management plus placebo. All treatments were manual-guided, delivered by experienced therapists, and monitored to promote the integrity of both forms of treatment. Results: First, although all groups showed significant improvement, significant main effects for medication or psychotherapy, or their combination, were not found for treatment retention, reduction in cocaine use, or other outcomes at 12 weeks. Second, baseline severity of cocaine use interacted differently with psychotherapy and pharmacotherapy: higher-severity patients had significantly better outcome when treated with relapse prevention than with clinical management, while desipramine was associated with improved abstinence initiation among lower-severity subjects. Third, desipramine was significantly more effective than placebo in reducing cocaine use over 6, but not 12, weeks of treatment. Fourth, depressed subjects had greater reduction in cocaine use than nondepressed subjects and had better response to relapse prevention than to clinical management. Conclusion: These findings underscore the significance of heterogeneity among cocaine abusers and the need to develop specialized treatments for clinically distinct subgroups of cocaine abusers.

Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram.

Abstract: The aim of the study was to investigate the efficacy and safety of the selective serotonin reuptake inhibitor citalopram in treating poststroke depression, since available treatments are usually poorly tolerated.A 6-week double-blind, placebo-controlled trial was undertaken. Diagnosis and outcome were determined using the Hamilton Depression Scale, and unwanted effects were measured using the UKU side effect rating scale. Sixty-six consecutive depressed patients from an unselected population of 285 stroke patients aged 25 to 80 years entered the trial 2 to 52 weeks after stroke. They were assigned to equally sized treatment and placebo groups. The initial level of depression was comparable in the two groups (mean baseline Hamilton Depression scores, 19.4 and 18.9, respectively). Demographic parameters were also comparable in the two groups.Significantly greater improvement was seen in patients treated with citalopram (10 to 40 mg/d) for 3 and 6 weeks, both when including all patients (intention-to-treat a...

Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia

Abstract: Objective. To compare the relative efficacy and tolerability of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia, and to identify predictors of response to amitriptyline and cyclobenzaprine. Methods, Two hundred eight patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered into a 6-month prospective, double-blind, multicenter trial and were randomized to 1 of 3 treatment groups: amitriptyline, cyclobenzaprine, or placebo. Results. After 1 month, 21%, 12%, and 0% of the amitriptyline, cyclobenzaprine, and placebo patients, respectively, had significant clinical improvement (amitriptyline versus placebo P = 0.002, cyclobenzaprine versus placebo P = 0.02, amitriptyline versus cyclobenzaprine P not significant). These percentages increased to 36%, 33%, and 19%, respectively, at the 6-month assessment (P not significant). The nature and frequency of side effects reported by patients treated with amitriptyline and those reported by patients treated with cyclobenzaprine were similar. A normal Minnesota Multiphasic Personality Inventory (MMPI) profile at baseline was predictive of clinical improvement at the 1-month evaluation (odds ratio 3.3, 95% confidence interval 1.2—9.0). However, neither the MMPI profile nor any of the demographic, clinical, or functional parameters evaluated at baseline predicted long-term response. Conclusion. Our data confirm the short-term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia. Long-term efficacy could not be demonstrated because of a higher-than-expected placebo response. Predictors of response to these drugs could not be determined.

Paroxetine treatment of premature ejaculation: a double-blind, randomized, placebo-controlled study.

Abstract: Seventeen male outpatients with premature ejaculation were randomly assigned to treatment with paroxetine (N = 8) or placebo (N = 9). After a first week dose of 20 mg/day, the paroxetine regimen was increased to 40 mg/day for 5 weeks. Patients and their female partners were interviewed separately. Patients treated with paroxetine had significantly greater clinical improvement than the patients given placebo.

Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin-D-replete elderly patients

Abstract: The efficacy of calcium (Ca) in reducing bone loss is debated. In a randomized placebo-controlled double-masked study, we investigated the effects of oral Ca supplements on femoral shaft (FS), femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD), and on the incidence of vertebral fracture in vitamin-D-replete elderly. Ninety-three healthy subjects (72.1±0.6 years) were randomly allocated to three groups receiving 800 mg/day Ca in two different forms or a placebo for 18 months. Sixty-three patients (78.4±1.0 years) with a recent hip fracture were allocated to two groups receiving the two forms of Ca without placebo. FS BMD changes in Ca-supplemented non-fractured women were significantly different from those in the placebo group (+0.6±0.5% v −1.2±0.7%,p<0.05). There was no difference in effect between the two forms of Ca. The changes of +0.7±0.8% v −1.7±1.6% in FN BMD of Ca-supplemented women and the placebo group did not reach statistical significance. In fractured patients, FS, FN and LS BMD changes were −1.3±0.8, +0.3±1.6 and +3.1±1.2% (p<0.05 for the last). The rate of new vertebral fractures was 74.3 and 106.2 fractures per 1000 patient-years in Ca-supplemented non-fractured subjects and in the placebo group, respectively, and 144.0 in Ca-supplemented fractured patients. Thus, oral Ca supplements prevented a femoral BMD decrease and lowered vertebral fracture rate in the elderly.

Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy.

Abstract: Objectives This meta-analysis was performed to determine whether corticosteroid therapy induces the development of peptic ulcer and other putative complications of steroid therapy. Design A retrospective investigation in which we analysed all the randomized, double-blind, controlled trials (RDBCT) in which steroids had been administered that we were able to identify. The number of episodes of peptic ulcer, dermatological effects, sepsis, diabetes, hypertension, osteoporosis, psychosis and tuberculosis reported in both the placebo and steroid groups were compared. Setting The international medical literature was analysed for any RDBCT in which any steroid or ACTH had been administered in any dosage for any duration, and any putative complication of steroid therapy was reported. Subjects Of 1857 articles, 93 satisfied our requirements and were analysed by the meta-analytic techniques of Peto, DerSimonian and Laird. A total of 6602 patients were included. Main outcome measures The relative frequencies of each of these eight 'complications' were compared in the placebo and steroid groups using conventional statistics and meta-analysis. The relative frequencies of 'annualized' subgroups of patients who received treatment for 1 to 7 days, 1 week to 1 month, 1 to 3 months and more than 3 months, were similarly analysed. Results Nine of 3267 patients in the placebo group (0.3%) and 13 of 3335 patients in the steroid group (0.4%) were reported to develop peptic ulcer (P > 0.05). The dermatological cosmetic effects of steroid therapy were observed more frequently in the steroid group (P Conclusions Peptic ulcer is a rare complication of corticosteroid therapy that should not be considered a contraindication when steroid therapy is indicated.

The effect of pulsed electromagnetic fields in the treatment of osteoarthritis of the knee and cervical spine. Report of randomized, double blind, placebo controlled trials.

Abstract: Objective We conducted a randomized, double blind clinical trial to determine the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee and cervical spine. Methods A controlled trial of 18 half-hour active or placebo treatments was conducted in 86 patients with OA of the knee and 81 patients with OA of the cervical spine, in which pain was evaluated using a 10 cm visual analog scale, activities of daily living using a series of questions (answered by the patient as never, sometimes, most of the time, or always), pain on passive motion (recorded as none, slight, moderate, or severe), and joint tenderness (recorded using a modified Ritchie scale). Global evaluations of improvement were made by the patient and examining physician. Evaluations were made at baseline, midway, end of treatment, and one month after completion of treatment. Results Matched pair t tests showed extremely significant changes from baseline for the treated patients in both knee and cervical spine studies at the end of treatment and the one month followup observations, whereas the changes in the placebo patients showed lesser degrees of significance at the end of treatment, and had lost significance for most variables at the one month followup. Means of the treated group of patients with OA of the knee showed greater improvement from baseline values than the placebo group by the end of treatment and at the one month followup observation. Using the 2-tailed t test, at the end of treatment the differences in the means of the 2 groups reached statistical significance for pain, pain on motion, and both the patient overall assessment and the physician global assessment. The means of the treated patients with OA of the cervical spine showed greater improvement from baseline than the placebo group for most variables at the end of treatment and one month followup observations; these differences reached statistical significance at one or more observation points for pain, pain on motion, and tenderness. Conclusion PEMF has therapeutic benefit in painful OA of the knee or cervical spine.

Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors.

Abstract: Eicosanoids may be important factors for tumor cell proliferation, metastatic formation, and development of cancer cachexia. The present study has evaluated the effect of anti-inflammatory treatment on tumor progression in clinical cancer. Patients ( n = 135) with insidious or overt malnutrition due to generalized malignancy (various kinds of solid tumors) and an expected survival of more than 6 months were randomized by a computer-based algorithm to receive placebo, prednisolone (10 mg twice daily), or indomethacin (50 mg twice daily) p.o. until death. Patient groups were stratified in the randomization procedure for sex, tumor type, stage, nutritional state, and previous tumor treatment, and biochemical, physiological, and some functional variables (Karnowsky index, fatigue and pain score). A majority of these variables was then registered during the follow-up. Indomethacin and prednisolone treatment maintained Karnowsky index, while placebo-treated patients experienced a decreased index. Indomethacin-treated patients suffered less pain and consumed less additional analgetics compared to the other patient groups. Indomethacin prolonged mean survival compared to placebo-treated patients from 250 ± 28 days to 510 ± 28 days ( P < 0.05). Survival analysis on observations from all patients treated with either indomethacin or prednisolone demonstrated a significantly prolonged survival by anti-inflammatory treatment compared to placebo treatment (log rank, P < 0.03). The results suggest that not only may prostaglandin synthesis inhibition offer palliative support to patients with solid advanced cancer, but it may also impact on pathways that ultimately determine outcome.

Intravenous nimodipine West European Stroke Trial (INWEST) of nimodipine in the treatment of acute ischaemic stroke

Abstract: A randomised, double-blind, placebo-controlled trial of intravenous nimodipine was conducted in 295 patients with acute ischaemic stroke. Nimodipine was given as an intravenous infusion of 1 or 2 mg/h for 5 days followed by an oral dose of 120 mg daily for a total treatment period of 21 days. Patients with a clinical diagnosis of ischaemic stroke in the carotid artery territory within 24 h entered the study at 34 centres, involving 11 European countries: 100 were randomly assigned to placebo, 101 to nimodipine with an initial intravenous dose of 1 mg/h and 94 patients to an initial dose of 2 mg/h. The trial, initially aiming at a patient inclusion of 600, was terminated because of concerns arising from safety monitoring. Primary efficacy variables were neurological outcome according to the Orgogozo scale and functional outcome according to the Barthel scale at day 21. There were apparent differences between the groups in neurological and functional outcome with a better outcome in the placebo group. The differences between the placebo group and the 2-mg/h group were statistically significant (p = 0.0005 for the Orgogozo scale and p = 0.0033 for the Barthel scale). The differences were even more pronounced at the final follow-up at 24 weeks (p = 0.0001 and p = 0.0002, respectively). There were no statistically significant differences in mortality between the groups. There were statistically significant differences between the groups regarding the effect of the first few days of intravenous treatment on systolic and diastolic blood pressure with the most pronounced reduction in the 2-mg/h nimodipine treatment group at day 2 (p = 0.0001). An explorative analysis indicated a correlation between diastolic blood pressure reduction in the nimodipine-treated groups and unfavourable neurological outcome (p = 0.0005). A potential neuroprotective effect of nimodipine by preventing calcium overload in ischaemic neurons may thus have been outweighed by detrimental haemodynamic effects in the ischaemic area.

Psychopharmacological treatment of social phobia; a double blind placebo controlled study with fluvoxamine

Abstract: Previous studies have shown selective and non-selective monoamine oxidase inhibitors (MAOIs) to be effective in the treatment of social phobia. In this study we investigated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in social phobia. Thirty patients with social phobia (DSM-IIIR) were treated with the SSRI fluvoxamine (150 mg daily) using a 12-week double-blind placebo controlled design. A substantial improvement was observed in seven (46%) patients on fluvoxamine and in one (7%) on placebo. Statistically significant effects were seen on measures of social anxiety and general (or anticipatory) anxiety in patients treated with fluvoxamine compared with placebo. The level of phobic avoidance decreased also but the difference at endpoint between fluvoxamine and placebo failed to reach statistical significance. It is concluded that treatment with the SSRI fluvoxamine has beneficial effects in patients suffering from social phobia, suggesting that serotonergic mechanisms might be implicated in social anxiety.

Garlic as a lipid lowering agent--a meta-analysis.

Abstract: Garlic supplements may have an important role to play in the treatment of hypercholesterolaemia. To determine the effect of garlic on serum lipids and lipoproteins relative to placebo and other lipid lowering agents, a systematic review, including meta-analysis, was undertaken of published and unpublished randomised controlled trials of garlic preparations of at least four weeks' duration. Studies were identified by a search of MEDLINE and the ALTERNATIVE MEDICINE electronic databases, from references listed in primary and review articles, and through direct contact with garlic manufacturers. Sixteen trials, with data from 952 subjects, were included in the analyses. Many of the trials had methodological shortcomings. The pooled mean difference in the absolute change (from baseline to final measurement in mmol/l) of total serum cholesterol, triglycerides, and high-density lipoprotein (HDL)-cholesterol was compared between subjects treated with garlic therapy against those treated with placebo or other agents. The mean difference in reduction of total cholesterol between garlic-treated subjects and those receiving placebo (or avoiding garlic in their diet) was -0.77 mmol/l (95% CI: -0.65, -0.89 mmol/l). These changes represent a 12% reduction with garlic therapy beyond the final levels achieved with placebo alone. The reduction was evident after one month of therapy and persisted for at least six months. In the dried garlic powders, in which the allicin content is standardised, there was no significant difference in the size of the reduction across the dose range of 600-900 mg daily. Dried garlic powder preparations also significantly lowered serum triglyceride by 0.31 mmol/l compared to placebo (95% CI: -0.14, -0.49).(ABSTRACT TRUNCATED AT 250 WORDS)