Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial

The analgesic effectiveness and adverse effect incidence of a daily dose of 10 or 20 mg of oral methadone were evaluated in 18 patients with a diverse range of chronic neuropathic pain syndromes, who had all responded poorly to traditional analgesic regimens. Analgesia was seen after each dose of methadone. As compared with placebo, the 20 mg daily dose (given as 10 mg bd) resulted in statistically significant (P = 0.013-0.020) improvements in patient Visual Analogue Scale ratings of maximum pain intensity, average pain intensity and pain relief, recorded at the same time daily. The analgesic effects extended over 48 hours, as shown by statistically significant (P = 0.013-0.020) improvements in all three outcomes on the rest days instituted between each daily dose. Analgesic effects (lowered maximum pain intensity and increased pain relief, on the day of dosing only) were also seen when the lower daily dose of 10 mg methadone (given as 5 mg bd) was used, but these failed to reach statistical significance (P = 0.064 and 0.065, respectively). Interpatient analysis showed that the analgesic effects were not restricted to any particular type of neuropathic pain. Patient compliance was high throughout the trial. One patient withdrew during the 10 mg and six during the 20 mg methadone treatment periods. This is the first double-blind randomized controlled trial to demonstrate that methadone has an analgesic effect in neuropathic pain.     

The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study.

BACKGROUND AND AIM: The aim of this randomized double blind placebo controlled study was to investigate the effectiveness and the safety of venlafaxine XR 75 and 150 mg on ongoing pain and on quantitative sensory tests in 60 patients with neuropathic pain for 8 weeks. METHODS: Evaluation parameters consisted of ongoing pain intensity (VAS), patient satisfaction, side effects, global efficacy and tolerance. Quantitative sensory measurements taken from the affected area before and after the drug treatment included pin-prick hyperalgesia, allodynia, detection and pain thresholds to electrical and heat stimuli, temporal summation of repetitive electrical and heat stimuli. RESULTS: A total of 55 patients completed the study. VAS scores decreased significantly compared to the baseline measurements in all groups. There was no significant difference between the groups regarding pain intensity and escape medication. The areas of allodynia and pin-prick hyperalgesia decreased significantly in venlafaxine groups compared to the placebo. There was no significant difference between the groups regarding the detection thresholds (electrical and heat). The pain threshold and the summation threshold to electrical stimuli and the summation threshold to heat stimuli increased significantly following treatment in both venlafaxine groups. In addition, the degree of the temporal summation to electrical and heat stimuli decreased significantly following treatment in both venlafaxine groups compared to the placebo. CONCLUSION: The study showed significant effect of venlafaxine in the manifestations of hyperalgesia and temporal summation, but not on the ongoing pain intensity. Furthermore, the quantitative sensory tests provided complementing information to the clinical measures.     

Cholesterol lowering effect of metformin in combined hyperlipidemia: placebo controlled double blind trial

Metformin, an antidiabetic biguanide derivative, prevents experimental atherosclerosis and induces structural changes in lipoproteins in experimental animals. In the present study we investigated the effect of metformin on serum lipoproteins and platelet function in 24 non-diabetic patients with type II B hyperlipidemia. The patients were randomly given metformin in two dosage levels (1.0 g/day and 2.0 g/day) and placebo for periods of nine weeks in a crossover trial. Metformin caused a dose dependent fall in the concentrations of total serum cholesterol and of LDL-cholesterol. The average concentration of total cholesterol was 8.54 +/- 0.22 (SE) mmol/l, 8.12 +/- 0.19 mmol/l and 7.79 +/- 0.15 mmol/l during placebo, metformin 1.0 g/day and 2.0 g/day treatments, respectively. Both metformin values differed significantly (P less than 0.05) from the placebo value. Thus there was an average fall of 8.1% in total cholesterol after the higher metformin dose. LDL-cholesterol was 5.25 +/- 0.23 mmol/l after placebo, falling by 3.1% and 9.6% after metformin doses of 1.0 g/day and 2.0 g/day, respectively. The concentrations of HDL-cholesterol and total serum triglycerides showed no significant changes. Body weight, blood glucose, plasma insulin, blood lactate, platelet function and urinary excretion of prostanoids remained unchanged during the study. The reduction of total- and LDL-cholesterol levels may be a welcome additional consequence of metformin during treatment of diabetic patients with hypercholesterolemia.     

Rofecoxib attenuates both primary and secondary inflammatory hyperalgesia: a randomized, double blinded, placebo controlled crossover trial in the UV-B pain model

The analysis of drug's influence on peripheral and central sensitisation can give useful information about its mode of action and can lead to more efficacy in the treatment of pain. Peripheral inflammation is associated with peripheral expression and up-regulation of cyclooxygenase 2 (COX-2) in the CNS. The relative contribution of COX-2 mediated central sensitisation may be prominent under inflammatory conditions. In this randomized, double blinded, placebo controlled cross-over trial the effects of multidoses of the COX-2 selective inhibitor rofecoxib on primary and secondary hyperalgesia were evaluated in the UVB pain model. Twenty-four hours after local UVB irradiation at the upper leg of 42 healthy volunteers heat pain perception (HPPT) and heat pain tolerance thresholds (HPTT) were assessed within the inflammation. The area of secondary hyperalgesia was determined by pin prick test. Subjects received oral rofecoxib 50, 250, 500 mg or placebo. Pain testing was repeated after 3 and 6 h. Compared to placebo, rofecoxib significantly increased HPPT (1.55 and 1.08 degrees C, P<0.0001 and P=0.0333), HPTT (1.74 and 1.58 degrees C, P<0.0001 and P<0.0001), and reduced the mean area of secondary hyperalgesia by 15.6% (P=0.007) and 16.8% (P<0.001) after 3 and 6 h. No significant difference between the three dosage groups was observed. These data confirm peripheral effects of rofecoxib in a human inflammatory UV-B pain model and provide circumstantial evidence that even a standard clinical dose of rofecoxib reduces central hyperalgesia in inflammatory pain. We confirm that the effect of single oral dose of rofecoxib plateaus at 50 mg.     

Laninamivir octanoate for post-exposure prophylaxis of influenza in household contacts: a randomized double blind placebo controlled trial

Laninamivir octanoate, a long-acting neuraminidase inhibitor, is an effective treatment for influenza. However, its effectiveness for the prevention of influenza has not yet been demonstrated. We conducted a double-blind, multicenter, randomized, placebo-controlled trial to determine whether laninamivir octanoate was superior to a placebo for post-exposure prophylaxis of influenza in household contacts. Eligible participants, who were household members who did not have influenza and were in contact with an influenza-infected index patient, were randomly assigned (1:1:1) to one of three groups: 20 mg of laninamivir octanoate once daily for 2 days (LO-2), 20 mg of laninamivir octanoate once daily for 3 days (LO-3), or a placebo. The primary endpoint was the proportion of participants who developed clinical influenza during a 10-day period. A total of 1711 participants were enrolled, and 1451 participants were included in the primary analysis. The proportion of participants with clinical influenza was 3.9 % (19/487) in the LO-2 group, 3.7 % (18/486) in the LO-3 group, and 16.9 % (81/478) in the placebo group (P < 0.001 for each of the laninamivir octanoate group). The relative risk reductions, compared with the placebo group, were 77.0 % [95 % confidence interval (CI) 62.7–85.8] and 78.1 % (95 % CI 64.1–86.7 %) for the LO-2 and LO-3 groups, respectively. The incidences of adverse events in the laninamivir octanoate groups were similar to that in the placebo group. The inhalation of 20 mg of laninamivir octanoate once daily for 2 or 3 days was well tolerated and effectively prevented the development of influenza in household contacts.     

Homeopathic treatment of migraine: a double blind, placebo controlled trial of 68 patients [see comment

To evaluate the efficacy of homeopathy in preventing migraine attacks and accompanying symptoms, a randomised, double-blind, placebo-controlled clinical trial was conducted. There was a one-month registration period without treatment, followed by four months individualised homeopathic treatment or identical placebo. Patients were stratified for common or classical migraine. Seventy-three patients were randomised, 68 completed the trial. Baseline values were similar in the two groups. Both the homeopathy and placebo groups had reduction in attack frequency, pain intensity and drug consumption, with a statistically non-significant difference favouring homeopathy. Migraine diaries showed no difference between groups. The neurologists' trial evaluation showed a statistically significant reduction in attack frequency in the homeopathy group (P= 0.04) and non-statistically significant trends in favour of homeopathy for pain intensity and overall evaluation. Further research, with improved trial design, on the possible role of homeopathy in migraine prophylaxis is justified.     

Study of analgesic efficacy of propacetamol in the postoperative period using a double blind placebo controlled method

The efficiency and safety of postoperative use of propacetamol was estimated in 30 patients by means of double blind placebo controlled method. The first group consisted of 15 patients to whom propacetamol was introduced intravenously in single dose of 2 g along with patient controlled anesthesia with promedol. Placebo in combination with patient control anesthesia were used in 15 patients from the 2nd group. Intravenous introducing of propacetamol in dose of 2 g in 15 minutes provides relief of pain intensity in postoperative period. So it permits to consider propacetamol as basic non-opioid analgesic. In early postoperative period combination of propacetamol and opioid analgesic (promedol) reduces demands in the latter by 44%.     

Gabapentin in postherpetic neuralgia: a randomised, double blind, placebo controlled study.

A multicentre double blind, randomised, placebo controlled 7-week study evaluated the efficacy and safety of gabapentin 1800 or 2400 mg/day in treating postherpetic neuralgia. Three hundred and thirty-four men and women aged at least 18 years (mean 73) received gabapentin 1800 or 2400 mg daily or placebo in three divided doses with a forced titration schedule. The primary outcome measure was change in average daily pain diary score (baseline week v final week). Secondary outcomes included mean weekly sleep interference score; Short Form-McGill Pain Questionnaire (SF-MPQ); Clinician and Patient Global Impression of Change (CGIC/PGIC); Short Form-36 Health Survey (SF-36). From week 1, pain scores showed a significantly greater improvement with gabapentin: the final difference v baseline was -34.5% for the 1800 mg dose, -34.4% for the 2400 mg dose compared with -15.7% for the placebo group. The difference vs. placebo was 18.8% for the 1800 mg dose (95% confidence interval 10.9-26.8%; P<0.01) and 18.7% for the 2400 mg dose (10.7-26.7%; P<0.01). Sleep interference diaries showed a similar pattern. There were significant differences in favour of gabapentin for number of patients reporting >50% reduction in their pain intensity, in the CGIC and PGIC, in the sensory and total scores of the SF-MPQ (both doses), in the visual analogue scale of pain of the SF-MPQ (2400 mg only) and in the vitality, bodily pain and mental health domains of the SF-36. Overall gabapentin was well tolerated. The most common adverse events were dizziness and somnolence, particularly during the titration phase. Thus, this study confirms the role of gabapentin as an efficacious and well-tolerated treatment for postherpetic neuralgia.     

A double blind trial of terfenadine and placebo in hay fever using a substitution technique for non-responders

A double-blind study of terfenadine and placebo in 110 patients suffering from hay fever (confirmed by skin tests) was conducted. A novel technique was applied using an escape envelope containing a reference drug which could be taken under controlled conditions if, after 48 hours, the patient experienced no relief. Significantly more patients on placebo opened the envelope than patients taking the active drug. Terfenadine was demonstrated to be an effective drug in hay fever and produced no more drowsiness than placebo.     

奥氮平治疗多发性抽动症:随机、对照、双盲试验

目的:多发性抽动症的治疗传统上以氟哌叮醇治疗为主,但其严重的锥体外系反应限制了其应用,为了解新一代精神药品奥氮平对多发性抽动症的疗效,与阳性对照药氟哌叮醇比较,评价奥氮平治疗多发性抽动症的疗效及其安全性。方法:实验于2003-06/2004-06在新乡医学院第二附属医院临床心理科完成。所有研究组对象均符合美国诊断和统计手册第四版(DSM-IV)的诊断,排除躯体疾病和其他精神疾病;对照组为与研究组相匹配的健康儿童。采用随机对照试验方法,将60例多发性抽动症症患者分成奥氮平组(5～10mg/d,30例)和氟哌叮醇组(4～12mg/d,30例),在3d清洗期后,进入疗程4周的治疗。采用YALE综合抽动严重程度量表、临床总体疗效评定量表和药物副反应量表来评价药物疗效和不良反应。结果:治疗后第4周奥氮平组总有效率72%,氟哌叮醇组总有效率72%。两组YALE综合抽动严重程度治疗后,第4周奥氮平组为7.48±6.78,氟哌叮醇组9.67±6.79,两组差有显著性意义(P<0.05),奥氮平药物不良反应明显减少。结论:奥氮平是一种有效、安全的抗抽动药物,有改善睡眠的作用,不良反应轻。     

Triglyceride lowering effect of MaxEPA fish lipid concentrate: a multicentre placebo controlled double blind study

A multicentre, double blind, randomised between-group study comparing the triglyceride lowering effect of MaxEPA, a natural marine oil, and a placebo control is described. Eighty-six patients with hypertriglyceridaemia (fasting serum triglyceride greater than or equal to 2 mmol/l) were studied for three months. There were no significant differences between the groups (48 active, 38 control) in respect of age, sex, height or weight, smoking habits or alcohol consumption. After one month triglyceride levels were reduced significantly from baseline in the treatment group and there was also a highly significant difference between the groups in favour of the marine oil. There was no significant change in serum total cholesterol in either group but there were fluctuations in high density lipoprotein (HDL) in both groups. Minor gastrointestinal side effects were reported by patients in both groups. Standard haematological and biochemical tests were done and there were no significant changes from baseline.     

Intravenous dipyrone in the acute treatment of migraine without aura and migraine with aura: a randomized,double blind,placebo controlled study

BACKGROUND: Dipyrone (Metamizol) has been used in the acute treatment of migraines in Brazil. Some investigators have found it to be a highly effective medication for migraine pain and associated symptoms. OBJECTIVE: To conduct a randomized, placebo controlled, double blind study to assess the effect of dipyrone on the pain and symptoms associated with migraine without aura or with aura and the adverse effect profile of this medication. METHODS: For the migraine without aura group, 44 patients were assigned at random to receive 1 g intravenous dipyrone, and 30 patients received 10 mL 0.9% physiological saline. For the migraine with aura group, 30 patients received both dipyrone or placebo. We used seven parameters of analgesic evaluation and an analog scale to assess nausea, photophobia, and phonophobia. RESULTS: Patients receiving dipyrone demonstrated a statistically superior improvement (P<.05 and P<.01) in pain and all associated symptoms compared with control subjects. CONCLUSIONS: Dipyrone is an effective drug for the relief of acute migraine pain and associated symptoms.     

Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy

BACKGROUND: Painful neuropathy is one of the most common long-term complications of diabetes mellitus and often proves difficult to relieve.METHODS: Patients with diabetic neuropathy with moderate or greater pain for at least 3 months, were evaluated for efficacy, safety and health-related quality of life (QOL) while receiving controlled-release (CR) oxycodone (OxyContin) or active placebo. Patients underwent washout from all opioids 2-7 days before randomization to 10 mg CR oxycodone or active placebo (0.25 mg benztropine) q12h. The dose was increased, approximately weekly, to a maximum of 40 mg q12h CR oxycodone or 1 mg q12h benztropine, with crossover to the alternate treatment after a maximum of 4 weeks. Acetaminophen, 325-650 mg q4-6h prn was provided as rescue.RESULTS: Thirty-six patients were evaluable for efficacy (21 men, 15 women, mean age 63.0+/-9.4 years). CR oxycodone resulted in significantly lower (P=0.0001) mean daily pain (21.8+/-20.7 vs. 48.6+/-26.6 mm VAS), steady pain (23.5+/-23.0 vs. 47.6+/-30.7 mm VAS), brief pain (21.8+/-23.5 vs. 46.7+/-30.8 mm VAS), skin pain (14.3+/-20.4 vs. 43.2+/-31.3 mm VAS), and total pain and disability (16.8+/-15.6 vs. 25.2+/-16.7; P=0.004). Scores from 6 of the 8 SF-36 domains and both summary scales, Standardized Physical Component (P=0.0002) and Standardized Mental Component (P=0.0338) were significantly better during CR oxycodone treatment. The number needed to treat to obtain one patient with at least 50% pain relief is 2.6 and clinical effectiveness scores favoured treatment with CR oxycodone over placebo (P=0.0001).CONCLUSION: CR oxycodone is effective and safe for the management of painful diabetic neuropathy and improves QOL.     

The effect of aminophylline on renal colic: a randomized double blind controlled trial

OBJECTIVE: To evaluate the efficacy of aminophylline infusion as a painkiller compared with placebo in patients with acute renal colic. PATIENTS AND METHODS: From March to August 2005, 141 patients with clinical renal colic, who were under 60 years of age, had no history of heart or hepatic failure, asthma, theophylline or beta blocker use, reaction to methylxantines, pregnancy or breast feeding, and were not prescribed spasmolytic or analgesics, entered our study. They were randomly assigned to receive either 375 mg of aminophylline or placebo infusion under double blind conditions. Pain intensity was recorded using a visual analog scale (VAS), before drug administration and 30 and 60 minutes afterwards. The drug effectiveness was defined as > or =40% decrease in pain intensity 60 minutes after the onset of infusion, without exacerbation during the following 4 hours. RESULTS: Seventy patients received aminophylline; it was effective in 45 (64%; 95% confidence interval 52-75%). Alternatively, placebo was effective in 12 of 71 control patients (17%; 95% confidence interval 9-28%); (P < 0.001). Thirty and 60 minutes after administration, aminophylline reduced pain by 24% and 39% respectively, as compared with 6% and 8% pain reduction in the placebo group. CONCLUSION: This prospective study provides remarkable information about the efficacy of aminophylline on pain relief and decreasing narcotic usage in symptomatic urinary calculi. It is safe, inexpensive, with minute side effects and can be considered a good alternative or additive to narcotic analgesics in the management of renal colic.