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PubMed2001

A double-blind, placebo-controlled, efficacy and safety study of topical gel formulation of 1% alprostadil (Topiglan) for the in-office treatment of erectile dysfunction.

OBJECTIVES: To asses the efficacy and safety of Topiglan (1% alprostadil in a formulation with 5% SEPA [soft enhancer of percutaneous absorption]) or placebo gel (0.25 mL) applied to the glans penis only in 60 patients with moderate to severe erectile dysfunction in a two-visit, in-office clinical trial. METHODS: During the first visit, open-label placebo gel was applied. At the second visit, blind, random allocation to Topiglan (n = 31) or placebo gel (n = 29) occurred. Thirty minutes after application, an erotic movie showing heterosexual sex began; at 45 minutes, a penile vibrator was used. Audiovisual and tactile stimulation were discontinued at 65 minutes, and the patient was observed until 90 minutes after application. At the scheduled time points, the erection response was assessed by both the investigator and the patient and signs and symptoms of tolerance were evaluated. RESULTS: Topiglan produced a greater angle of erection (P = 0.003) and maximum rigidity (P = 0.033) compared with the placebo gel. The responses to Topiglan were greater than to placebo gel at all time points after application, with the greatest differences observed at 45 and 60 minutes. Of the 31 patients treated with Topiglan, 12 (38.9%) achieved an erection judged sufficient for vaginal penetration (P = 0.005); 2 (6.9%) of the 29 patients who received placebo gel did so. Penile erythema was more common with Topiglan; symptoms of minor to mild warmth or burning and, less commonly, tingling and coolness were reported by most patients after both Topiglan and placebo gel application. No significant changes in vital signs were noted. CONCLUSIONS: Topiglan applied to the glans penis increased penile rigidity and expectations regarding vaginal penetration in patients with erectile dysfunction.

Administration, Cutaneous↗

PubMed2003

Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia.

OBJECTIVES: To evaluate the incidence and resolution of sexual adverse experiences (AEs) in men with benign prostatic hyperplasia treated with finasteride 5 mg compared with placebo. METHODS: The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men, aged 45 to 78 years, with symptomatic benign prostatic hyperplasia, enlarged prostates, and no evidence of prostate cancer. Patients completed a questionnaire at screening regarding their history of sexual dysfunction. During treatment, spontaneously self-reported sexual AEs were recorded. RESULTS: At screening, 46% of patients in each treatment group reported some history of sexual dysfunction. During year 1 of the study, 15% of finasteride-treated patients and 7% of placebo-treated patients had sexual AEs that were considered drug related by the investigator (P <0.001). During years 2 to 4, no between-group difference was noted in the incidence of new sexual AEs (7% in each group). The drug-related sexual AE profile for finasteride was similar for men with or without a history of sexual dysfunction. Sexual AEs resolved while continuing therapy in 12% of finasteride patients and 19% of placebo patients. Only 4% of finasteride and 2% of placebo patients discontinued the study because of sexual AEs. In men who discontinued with a sexual AE, 50% and 41% experienced resolution of their sexual AE after discontinuing finasteride or placebo therapy, respectively. CONCLUSIONS: Compared with placebo, men treated with finasteride experienced new drug-related sexual AEs with an increased incidence only during the first year of therapy.

Aged↗

PubMed1997

A randomised, prospective, double-blind, placebo-controlled trial of glyceryl trinitrate ointment in treatment of anal fissure.

BACKGROUND: Anal fissure is most commonly treated surgically by internal anal sphincterotomy. However, there is some concern over the effects of this procedure on continence. Nitric oxide donors such as glyceryl trinitrate (GTN) have been shown to cause a reversible chemical sphincterotomy capable of healing fissures in a small series of cases. This study reports a prospective, randomised, double-blind, placebo-controlled trial to test the hypothesis that topical GTN is the best first-line treatment for chronic anal fissure. METHODS: 80 consecutive patients were randomised to receive treatments with topical 0.2% GTN ointment or placebo. Maximum anal resting pressure (MARP) was measured with a constantly perfused side-hole catheter before and after the first application of trial ointment. Anodermal blood flow was measured during manometry by laser Doppler flowmetry. After initial treatments, patients were given a supply of ointment (either GTN or placebo) to be applied to the lower anal canal twice daily. Patients were reviewed 2-weekly. At the initial and follow up visits patients were asked to record pain experienced on defaecation on a linear analogue pain score. Endpoints were healing of the fissure or condition after 8 weeks of treatment. FINDINGS: After 8 weeks, healing was observed in 26/38 (68%) patients treated with GTN and in 3/39 (8%) patients treated with placebo (p < 0.0001, chi 2 test). Linear analogue pain score fell significantly in both groups after 2 weeks of treatment. This fall was maintained in those treated with GTN but pain scores returned to pre-treatment values by 4 weeks on treatment with placebo. MARP fell significantly from a mean of 115.9 (SD 31.6) to 75.9 (30.1) cm H2O (p < 0.001, Student's paired t-test) in patients treated with GTN but no change was seen in MARP after placebo. Anodermal blood flow measured by laser Doppler flowmetry significantly increased after application of GTN ointment but was unaffected by placebo. INTERPRETATION: Topical GTN provides rapid, sustained relief of pain in patients with anal fissure. Over two-thirds of patients treated in this way avoided surgery which would otherwise have been required for healing. Long-term follow up is needed to assess the risk of recurrent fissure in patients with GTN.

Administration, Topical↗

PubMed1997

Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group.

BACKGROUND: Multiple sclerosis is an autoimmune disorder characterised by the repeated occurrence of demyelinating lesions within the central nervous system. Uncontrolled studies and experimental evidence suggest beneficial effects of repeated administration of intravenous immunoglobulin (IVIg) by immunomodulating mechanisms and induction or remyelination. We aimed to investigate the efficacy of IVIg in a randomised double-blind multicentre study. METHODS: Patients with relapsing-remitting multiple sclerosis were randomly assigned a monthly dose of IVIg (0.15-0.2 g/kg bodyweight) or placebo. Duration of treatment was 2 years. The primary outcome measures were the effect of treatment on clinical disability-measured by the absolute change in Kurtzke's expanded disability status scale (EDSS) score- and the proportion of patients with improved, stable, or worse clinical disability (> or = 1.0 grade on EDSS score). FINDINGS: Of the 243 patients screened, 150 met our eligibility criteria and were randomly assigned to IVIg or placebo. Before the start of treatment two patients in the placebo group dropped out, so there were 75 patients in the IVIg group and 73 in the placebo group. Intention-to-treat analysis showed that IVIg treatment had a beneficial effect on the course of clinical disability. The EDSS score decreased in the IVIg-treated patients and increased in the placebo group (-0.23 [95% CI -0.43 to -0.03] vs 0.12 [-0.13 to 0.37], p = 0.008). In the IVIg group, the numbers of patients with improved, stable, or worse clinical disability were 23 (31%), 40 (53%), and 12 (16%) compared with ten (14%), 46 (63%), and 17 (23%) in the placebo group. Side-effects were reported in three (4%) IVIg-treated patients and in four (5%) placebo-group patients, but were not directly linked to study medication. INTERPRETATION: Monthly IVIg is an effective and well-tolerated treatment for patients with relapsing-remitting multiple sclerosis.

Adult↗

PubMed1998

Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study.

BACKGROUND/AIMS: In the current state of knowledge of the pathophysiology of hepatic encephalopathy, a reduction in hyperammonemia is the most important evidence of effective treatment. Therefore, the therapeutic efficacy of oral L-ornithine-L-aspartate, which improves impaired ammonia detoxification, was investigated in patients with cirrhosis, hyperammonemia and stable, overt, chronic hepatic encephalopathy, and in subclinical hepatic encephalopathy in a randomized, double-blind, placebo-controlled clinical trial. METHODS: Oral L-ornithine-L-aspartate was administered three times daily at fixed times for 14 consecutive days in a total dose of 18 g per day. The design was chosen to prevent an increase in ammonia induced by a protein meal of 0.25 g/kg body weight, given at the start of the daily treatment period. Efficacy variables were: fasting and postprandial ammonia concentration, Number-Connection-Test time, mental state grades, and a Portosystemic Encephalopathy Index. Analyses were based on the total study sample of 32 placebo- and 34 L-ornithine-L-aspartate-treated patients as well as on the subgroup samples in the overt (20 placebo- and 23 L-ornithine-L-aspartate-treated) and subclinical hepatic encephalopathy (12 placebo- and 11 L-ornithine-L-aspartate-treated) patients. RESULTS: Number Connection Test performance times (p<0.01) as well as fasting (p<0.01) and postprandial (p<0.05) venous blood ammonia concentrations in the L-ornithine-L-aspartate-treated group showed improvement in comparison to placebo. Also, the mental state grade (p<0.05) and the Portosystemic Encephalopathy Index (p<0.01), improved to a much greater degree in the L-ornithine-L-aspartate group than in the placebo group. Adverse events were observed in neither the placebo nor the L-ornithine-L-aspartate-treated patients. CONCLUSION: Oral L-ornithine-L-aspartate is a safe, well-tolerated treatment with a good compliance rate and a beneficial therapeutic effect in patients with cirrhosis and stable, overt, chronic hepatic encephalopathy.

Administration, Oral↗

PubMed2001

Impact of experimentally-induced expectancy on the analgesic efficacy of tramadol in chronic pain patients: a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial.

Variations in treatment effects between drug trials are usually attributed to different patient characteristics, variations in outcome assessment, and random error. We have previously hypothesized that part of the variation in treatment effects between drug trials might be caused by differences in nonspecific factors. In a randomized clinical trial, we aimed to investigate whether experimentally induced expectancy can modify the analgesic effect of tramadol relative to placebo in chronic pain patients. In a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial, chronic pain patients attending a chronic pain outpatient clinic were randomized to receive a single oral dose of 50 mg tramadol or placebo, and they were further randomized to receive positive or neutral information, verbally expressed by the physician, regarding the expected analgesic effect of the drug. Pain intensity was measured using a 10 centimeter visual analogue scale at baseline, and 0.5, 1, 2, 4, 6, and 8 hours after baseline. The one-hour pain intensity difference, calculated as the sum of pain intensity differences between baseline and 0.5 and 1 hour, was taken as main outcome measure. The one-hour sum of pain intensity differences of 28 patients treated after positive expectation and randomized to tramadol was 1.4 cm, while in 27 patients randomized to placebo, it was 0.8 cm. This corresponds with an analgesic effect of tramadol relative to placebo of 0.6 cm (95% confidence interval [CI], -0.5 cm to 1.8 cm). The 28 patients in the neutral expectancy group who were randomized to tramadol reported a 1.4 cm decrease on the sum of pain intensity differences, while 28 patients in the placebo group reported a 0.9 cm decrease. This corresponds with an analgesic effect of tramadol relative to placebo of 0.5 cm (95% CI, -0.9 cm to 1.8 cm). The 0.1 cm difference (0.6 cm - 0.5 cm) in analgesic effect between positive and neutral expectancy group was not statistically significant (95% CI, -0.7 cm to 1.0 cm). This trial did not discern a significant difference in the analgesic effect of tramadol between a positive and neutral expectancy group. This means that the phenomenon either does not exist, or we had an inappropriate model to demonstrate it. Regardless, this study demonstrates the type of quality trial that should be done to find out which non-specific factors, such as information regarding the expected effect, can modify treatment effects.

Adult↗

PubMed1994

Efficacy of diclofenac sodium ophthalmic solution versus placebo in reducing inflammation following cataract extraction and posterior chamber lens implantation.

One hundred forty-eight patients were enrolled in a randomized, prospective, placebo-controlled clinical trial evaluating the efficacy of diclofenac sodium (Voltaren Ophthalmic) in reducing ocular inflammation following extracapsular cataract extraction with posterior chamber intraocular lens implantation. Eligible patients were enrolled and randomized (2:1 diclofenac:placebo) if the sum of anterior chamber cells plus flare one day postoperatively (baseline) was at least four. None of the patients received concomitant steroidal anti-inflammatory treatment. The 99 patients receiving diclofenac sodium had significantly greater improvement from baseline in summed flare plus cell score than the 49 placebo patients at two to five days and seven to nine days after baseline. Similarly, diclofenac sodium patients had significantly less post-baseline conjunctival erythema and ciliary flush than placebo patients. Significantly more diclofenac sodium patients than placebo patients showed moderate to marked improvement from baseline in overall assessment of inflammatory response. Forty-nine percent of placebo patients but only 17% of diclofenac patients were considered therapeutic failures (P < .001). By five to seven days, 82% of diclofenac sodium patients and 59% of placebo patients had corrected visual acuities of 20/40 or better (P < .001). There were no clinically important differences in mean intraocular pressure at any visit.

Aged↗

PubMed2002

What are the main methodological problems in the estimation of placebo effects?

Researchers disagree whether placebo effects are clinically important. The controversy is partly due to conceptual and methodological problems. The objective of this paper is to analyze the main methodological problems in the estimation of placebo effects. Variations in the meaning of the concept of placebo effect are described, and the main methodological problems are analyzed. The notion of placebo effect has at least two main meanings: effect of placebo intervention, and effect of patient-provider interaction. When the terms are defined pragmatically, effects of placebo can be estimated as the difference between placebo and no-treatment in randomized trials. The effect of patient-provider interaction can similarly be assessed by comparing manipulation of the patient-provider interaction with no manipulation. In both cases bias due to lack of double-blinding is a potential problem.

Confounding Factors, Epidemiologic↗

PubMed2003

A method for controlling for a high placebo response rate in a comparison of venlafaxine XR and diazepam in the short-term treatment of patients with generalised anxiety disorder.

This randomised, double-blind, placebo-controlled study compared the efficacy of venlafaxine XR (75 or 150 mg/d) with diazepam (15 mg/d) over an 8-week treatment period in 540 non-depressed outpatients with generalised anxiety disorder (GAD). At week 8, significant improvements from baseline were observed in the venlafaxine XR, diazepam and placebo groups. Although these improvements were higher in the first two groups than in the placebo group for each of the primary efficacy variables (Hamilton Rating Scale for Anxiety (HAM-A) total, HAM-A psychic anxiety factor, Hospital Anxiety and Depression Scale (HAD) anxiety sub-scale and Clinical Global Impression (CGI) improvement), there were no statistically significant differences between groups. These non-positive results were thought to be due to the very high placebo response observed in some centres. To understand the variability of the study, a secondary preplanned analysis was performed. This involved sub-dividing the study centres according to their ability to detect a two-point mean difference between diazepam and placebo at week 8 on the HAM-A total score. Centres able to show such a difference were termed verum-sensitive. Improvements from baseline to week 8 in venlafaxine XR-treated patients from verum-sensitive centres were significantly greater than in placebo on each of the primary efficacy measures (P </= 0.05). This suggests that those centres able to detect an anxiolytic effect of diazepam were also able to detect an anxiolytic effect of venlafaxine XR. Significant differences in baseline demographics, rates of adverse event reporting and rates of patient discontinuations were noted between patients enrolled at verum-sensitive and verum-insensitive sites. These results reflect the importance of study centre selection in accurately determining efficacy in placebo-controlled trials.

Adult↗

PubMed2003

A meta-analysis of sleep changes associated with placebo in hypnotic clinical trials.

OBJECTIVES: The effects associated with placebo (EAP) have been incompletely described in clinical trials of insomnia treatment. We conducted a meta-analysis of insomnia medication trials for the purpose of estimating the magnitude of sleep EAP. METHOD: We reviewed Medline for 1966 through 2000 for the meta-analysis. The subject heading of insomnia restricted to the subheading of drug therapy was crossed against the results of a search on the subjects heading placebo and text word placebo. We selected only papers that examined primary insomnia, incorporating both placebo and active medication therapies in a randomized, double-blind, parallel-group design. We required that results be reported for 1, 2, 3, or 4 weeks of treatment, and that outcomes be reported in hours/minutes. RESULTS: Five papers satisfied our requirements for eligibility, comprising 213 patients receiving placebo for a 2-week interval. Subjective sleep latency demonstrated a significant reduction (mean+/-S.E.) of 13.1+/-2.0 min (95% confidence interval (CI) 9.2, 17.0) for the placebo group after combining the data across studies. Subjective total sleep time demonstrated a significant increase of 13.5+/-5.4 min (95% CI 2.9, 24.0). Polysomnographic (PSG) sleep latency demonstrated a non-significant reduction of 2.5+/-4.3 min (95% CI -5.9, 10.9). CONCLUSIONS: The confirmation of EAP in insomnia clinical trials argues for the retention of a placebo control in future insomnia clinical trials.

Humans↗

PubMed2002

[Placebo: an unappreciated factor in medicine].

Placebo is a provoking factor in medicine that is discussed controversially and not fully understood so far. From the scientific point of view and according to evidence-based medicine a proved indication to prescribe a placebo does not exist. Therapy of pain may be an exclusion. In our daily work we consciously use the placebo-effect, but on the other hand we are committed to the placebo-phenomenon. This article gives an overview of various aspects of placebo. The currently supported theory about the placebo response, conditioning and expectancy, are discussed. Further, the side effects (nocebo-phenomenon) and the utility of placebo in randomised clinical trials is highlighted.

Controlled Clinical Trials as Topic↗

PubMed1983

Resolving the relationships between placebos, misattribution, and insomnia: an individual-differences perspective.

In Storms and Nisbett's (1970) original study of therapeutic misattributions, insomniacs given a placebo "arousal" pill went to sleep faster, whereas insomniacs given a placebo "relaxer" pill took longer than usual to fall asleep. This reverse placebo effect has been difficult to replicate; indeed, in several instances significant placebo effects have been obtained. In the present study we reasoned that insomniacs who are more attentive to internal bodily processes would be more apt to yield a reverse placebo effect, whereas those attentive to external stimuli would be more likely to be directly influenced by the suggested effects of the placebo. Thirty insomniacs completed trait measures of private body consciousness, private self-consciousness, and self-esteem. The procedure of Storms and Nisbett was then replicated. As predicted, subjects with high private body consciousness exhibited a stronger reverse placebo effect than did those subjects low on this dimension. Subsequent analyses revealed that this effect was entirely attributable to the low- rather than to the high-self-esteem participants. The effect of private self-consciousness was nonsignificant in all analyses. Theoretical implications are discussed.

Arousal↗

PubMedDate not supplied

Placebo and naloxone can alter post-surgical pain by separate mechanisms.

The discovery of an endogenous opioid-mediated analgesic system has led to the search for its physiological roles and how it might be activated in natural conditions. Environmental and surgical stress and certain forms of transcutaneous electrical stimulation or acupuncture appear to activate this system. Several studies also suggest that this opioid system mediates placebo analgesia. Placebo reduces post-surgical pain in comparison with no treatment, and this analgesia is apparently reversed by the opioid antagonist, naloxone. However, these studies did not indicate whether naloxone and placebo exert their effects by common or by separate mechanisms. By administering hidden infusions of naloxone (in subjects unaware that the medication was being given) separate from the administration of a placebo, we were able to assess the effects of these two treatments independently. We report here evidence that placebo analgesia can occur after blockade of opioid mechanisms by naloxone and that naloxone can produce hyperalgesia independent of the placebo effect. The combined action of these effects is sufficient to explain the reversal of placebo analgesia by naloxone.

Endorphins↗

PubMed2022

Polygenic heterogeneity in antidepressant treatment and placebo response.

The genetic architecture of antidepressant response is poorly understood. Polygenic risk scores (PRS), exploration of placebo response and the use of sub-scales might provide insights. Here, we investigate the association between PRSs for relevant complex traits and response to vortioxetine treatment and placebo using clinical scales, including sub-scales and self-reported assessments. We collected a clinical test sample of Major Depressive Disorder (MDD) patients treated with vortioxetine (N = 907) or placebo (N = 455) from seven randomized, double-blind, clinical trials. In parallel, we obtained data from an observational web-based study of vortioxetine-treated patients (N = 642) with self-reported response. PRSs for antidepressant response, psychiatric disorders, and symptom traits were derived using summary statistics from well-powered genome-wide association studies (GWAS). Association tests were performed between the PRSs and treatment response in each of the two test samples and empirical p-values were evaluated. In the clinical test sample, no PRSs were significantly associated with response to vortioxetine treatment or placebo following Bonferroni correction. However, clinically assessed treatment response PRS was nominally associated with vortioxetine treatment and placebo response given by several secondary outcome scales (improvement on HAM-A, HAM-A Psychic Anxiety sub-scale, CPFQ & PDQ), (P ≤ 0.026). Further, higher subjective well-being PRS (P ≤ 0.033) and lower depression PRS (P = 0.01) were nominally associated with higher placebo response. In the self-reported test sample, higher schizophrenia PRS was significantly associated with poorer self-reported response (P = 0.0001). The identified PRSs explain a low proportion of the variance (1.2-5.3%) in placebo and treatment response. Although the results were limited, we believe that PRS associations bear unredeemed potential as a predictor for treatment response, as more well-powered and phenotypically similar GWAS bases become available.

Humans↗

PubMed2002

An evaluation of the effects of high-dose fexofenadine on the central nervous system: a double-blind, placebo-controlled study in healthy volunteers.

BACKGROUND: As regards central nervous system (CNS) effects there are three types of antihistamines. Those that cross the blood-brain barrier and cause widespread impairment of cognitive and psychomotor function; those that cross into the brain and, although without much impairment at low clinical doses, have a dose-related relationship to impairment; and those that do not cross into the brain and therefore possess no intrinsic potential for impairing CNS function. OBJECTIVE: [corrected] To investigate the acute effects of fexofenadine (360 mg) on various aspects of cognitive and psychomotor function in comparison to placebo and promethazine (positive internal control), an antihistamine known to produce psychomotor and cognitive impairment. METHODS: Fifteen healthy volunteers received fexofenadine 360 mg, promethazine 30 mg and placebo in a 3-way cross-over, double-blind study. For each treatment condition, subjects were required to perform a series of tests of cognitive function and psychomotor performance at baseline and 1, 3, 5 and 7 h post-dose. The test battery consisted of critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking task (CTT) and a subjective assessment of sedation (LARS). RESULTS: Fexofenadine was not distinguishable from placebo in any of the objective and subjective tests for up to seven hours following drug administration. However, all measures were significantly impaired following the administration of promethazine, which confirms the sensitivity of the test battery for sedation. The effects of fexofenadine and placebo were not significantly different from one another, whereas promethazine caused an overall reduction in CFF thresholds when compared to placebo (P < 0.05). There was an overall significant increase (impairment) in recognition, motor and total reaction time (P < 0.05), and both the tracking accuracy and reaction time aspects of CTT were significantly impaired (P < 0.05) following the administration of promethazine. In contrast, the effects of fexofenadine could not be distinguished from the placebo condition. Subjective ratings of sedation were significantly higher with promethazine when compared to placebo (P < 0.05) and fexofenadine (P< 0.05). CONCLUSIONS: Fexofenadine at a dose of 360mg is demonstrably free from disruptive effects on aspects of psychomotor and cognitive function in a study where the psychometric assessments have been shown to be sensitive to impairment, as evidenced by the effects of the verum control promethazine 30 mg. The identification of an antihistamine (fexofenadine) devoid of central effects even at supraclinical doses separates it from currently available first and second generation drugs with no objective evidence of CNS side-effects on cognition and psychomotor function, and highlights the need for the introduction of a third generation of non-sedative antihistamines.

Adult↗

PubMed1999

Comparison of acarbose and metformin in patients with Type 2 diabetes mellitus insufficiently controlled with diet and sulphonylureas: a randomized, placebo-controlled study.

AIMS: To compare the efficacy and safety of acarbose and metformin when added to sulphonylurea therapy in diabetic patients insufficiently controlled with sulphonylureas alone. METHODS: A 12-week, single-centre, placebo-controlled study, with 89 patients randomized to receive acarbose (100 mg t.d.s.), metformin (850 mg b.d.) or placebo in addition to their sulphonylurea therapy. The study was double-blinded with respect to acarbose/placebo and single-blinded for metformin/ acarbose and metformin/placebo. Patients started a strict dietary regimen 1 week before receiving their first dose of acarbose, metformin or placebo. This regimen was individually adjusted to metabolic status and energy requirements. RESULTS: The primary endpoint, HbA1c, decreased from baseline in all three groups after 12 weeks. The decrease was greater in the two groups receiving active therapy compared with placebo (acarbose -2.3+/-0.32%; metformin -2.5+/-0.16%; placebo -1.3+/-0.34%). There was no significant difference between acarbose and metformin (P=0.65). Differences between both active therapies and placebo were statistically significant (acarbose P < or = 0.01; metformin P < or = 0.004). Reductions in body weight over the treatment period were seen in all three groups and were greatest in the acarbose group (median weight reduction: acarbose 3.5 kg; metformin, 1.0 kg; placebo 1.4 kg). There were no significant differences in the incidence of gastrointestinal side-effects between the three groups and all regimens were generally well tolerated. CONCLUSION: The results of the study demonstrate the equivalence of acarbose and metformin for improving metabolic control in patients insufficiently controlled with diet and sulphonylureas.

Acarbose↗

PubMed1999

Acute treatment of migraine attacks: efficacy and safety of a nonsteroidal anti-inflammatory drug, diclofenac-potassium, in comparison to oral sumatriptan and placebo. The Diclofenac-K/Sumatriptan Migraine Study Group.

BACKGROUND: Migraine attacks are often treated with simple analgesics or with ergotamine-containing preparations alone or in combination with anti-emetics. Although also sometimes used to treat migraine, nonsteroidal anti-inflammatory drugs (NSAIDs) have not been systematically evaluated in controlled clinical trials, particularly in comparison with the newer drug sumatriptan. Sumatriptan is a specific migraine treatment which has recently become among the most widely prescribed acute migraine therapies. However, while effective, it has low oral bioavailability and some problematic adverse effects. Diclofenac-potassium is a potent NSAID available as a fast-acting oral tablet, which has been shown to be safe and effective in several other acute pain indications. In the clinical trial reported here, the efficacy and safety of diclofenac-potassium in the acute treatment of migraine attacks has been tested in comparison with oral sumatriptan and placebo. METHODS: Single oral doses of 50 mg and 100 mg diclofenac-potassium were compared to a single oral dose of 100 mg sumatriptan and placebo in a double-blind randomized crossover trial in 156 adult patients suffering from migraine attacks, with or without aura, selected according to the International Headache Society diagnostic criteria. The primary efficacy criterion was migraine headache pain recorded on a visual analog scale at 2 h after dosing. Secondary endpoints included pain at other time points up to 8 h and the presence of accompanying symptoms (nausea, vomiting, photophobia, phonophobia). FINDINGS: Diclofenac-potassium was more effective than placebo in reducing migraine headache pain at 2 h after dosing, which was the primary endpoint. Secondary analyses showed that diclofenac-potassium provided significant pain relief from 60 min after dosing and for all remaining endpoints in the 8-h observation period. Both 50 and 100 mg doses of diclofenac-potassium were similarly effective. A similar effect was shown with sumatriptan; however, significant superiority to placebo was seen only from the 90-min time point. Diclofenac-potassium was generally superior to placebo or sumatriptan in reducing accompanying symptoms, particularly nausea. Diclofenac-potassium seemed to be as well tolerated as placebo, with fewer adverse events reported than after sumatriptan treatment and with more patients assessing the overall tolerability of diclofenac-potassium better than that of sumatriptan. INTERPRETATION: Compared with placebo and the reference therapy sumatriptan, diclofenac-potassium is an effective, fast-acting, and well-tolerated acute oral therapy for migraine attacks, with advantages over oral sumatriptan in terms of onset of analgesic effect, reduction of accompanying symptoms, and tolerability profile. It may therefore be useful as an alternative oral therapy for migraine attacks.

Administration, Oral↗

PubMed2003

Placebo response in clinical randomized trials of analgesics in migraine.

The objective was to assess the placebo response in randomized clinical trials of analgesics in the treatment of migraine attacks. We included placebo-controlled studies that used the criteria of the International Headache Society for the diagnosis of migraine and headache response as the primary efficacy parameter. In the 11 studies that qualified for inclusion, headache response occurred after placebo treatment in 7-50% of the migraineurs with an average placebo response rate of 30% (95% confidence interval (CI) 23-36). Two hours after treatment with placebo an average of 9% (95% CI 7-12, range 7-17%) of the patients were found to be pain free. In conclusion, the average headache response rate to placebo was 30% in randomized clinical trials of analgesics in migraine with a tremendous variation among studies. Placebo response rates vary with the choice of primary efficacy measure as well as patient characteristics and study design.

Analgesics↗