Citalopram in patients with fibromyalgia--a randomized, double-blind, placebo-controlled study.

The effect of the selective serotonin reuptake inhibitor citalopram was studied in a randomized, double-blind, placebo-controlled, 4-month trial in patients with the fibromyalgia syndrome (FMS) who all fulfilled the American College of Rheumatology criteria. The citalopram doses varied between 20-40 mg daily. Forty female patients, 21 patients in the citalopram and 19 in the placebo group, participated. Assessment of pain, depressive symptoms and physical functioning were made using Visual Analogue Scales (VAS), the Montgomery Asberg Depression Rating Scale (MADRS) and the Fibrositis Impact Questionnaire (FIQ).In the global judgement of improvement, no significant changes were found between the citalopram and placebo groups as concerns pain or well-being, either in the Intention to Treat (ITT) analysis or in the completer analysis. However, among the completers, it was a tendency that more patients in the citalopram group (52.9%) were improved as compared to the placebo group (22.2%) concerning well-being. Furthermore, the results indicated that treatment with citalopram had a significant effect on pain on the VAS after 2 months of treatment compared to baseline. After 4 months, however, the effect had diminished. Measured with the FIQ, significant differences in the pain ratings were seen at the end of the trial. Significant effects on the depressive symptomatology measured by means of the MADRS were seen already after 1 month of treatment and were increasing further at the end of the trial, when a significant difference between the groups was also found.     

Pharmacokinetics and pharmacodynamics of once-weekly subcutaneous epoetin alfa in critically ill patients: results of a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To describe the erythropoietin pharmacokinetic profile after once-weekly epoetin alfa treatment in critically ill patients. Secondary objectives were to compare pharmacodynamic and safety profiles between active treatment and placebo in these patients. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Medical, surgical, or mixed medical/surgical intensive care units. PATIENTS: A total of 73 anemic critically ill adults with an expected stay of >3 days and a hematocrit value of <38%. INTERVENTIONS: Patients were randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once weekly (n=48) or matching placebo (n=25) for up to 4 wks. MEASUREMENTS AND MAIN RESULTS: Serum erythropoietin concentration and hematologic variables (percentage reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts) were measured, and area under the serum concentration-time curve from time 0 to the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0-Tlast) for these three variables was determined. Mean serum erythropoietin concentrations in placebo patients were slightly higher than typical physiologic levels of erythropoietin in healthy subjects, although not appropriate for the degree of anemia in these patients. Overall, exposure of endogenous erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20% of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher with epoetin alfa than with placebo and was related to the AUC of erythropoietin. There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between epoetin alfa and placebo groups, which was most likely due to bleeding and transfusion events. Epoetin alfa was safe and well tolerated, with a rate of treatment-emergent complications similar to that seen with placebo. CONCLUSION: Epoetin alfa, once weekly, augmented the erythropoietic response in critically ill patients as indicated by the increased erythropoietin levels and larger AUC(RETI)0-Tlast in treated patients.     

Patient preference for once-weekly alendronate 70 mg versus once-daily alendronate 10 mg: a multicenter,randomized, open-label,crossover study

BACKGROUND: Alendronate, an oral bisphosphonate, is available for the treatment of osteoporosis in a 70-mg once-weekly and a 10-mg once-daily formulation. OBJECTIVES: This study aimed to determine patient preference for once-weekly versus once-daily dosing with alendronate, and to determine which treatment regimen the patients believed was more convenient and would be easier to comply with for a long period. METHODS: This was a multicenter, randomized, open-label, preference study in which postmenopausal women with osteoporosis were enrolled to receive 9 weeks of treatment in crossover fashion (4 weeks with each study regimen separated by a 1-week washout period). The study regimens included once-weekly alendronate 70 mg and once-daily alendronate 10 mg. The primary and secondary end points were assessed with a questionnaire completed by the patient. Adverse events (AEs) were recorded to assess patient tolerability of the study medications. RESULTS: A total of 324 patients met the eligibility requirements; 288 were randomized to treatment, 287 (mean age, 64.8 years) received treatment, 272 completed the questionnaire, and 266 completed the study. Of the patients who completed the questionnaire, 235 patients preferred the 70-mg once-weekly dosing regimen compared with the 10-mg once-daily regimen (86.4% vs 9.2%; P < 0.001). Most patients also believed that once-weekly dosing was more convenient than once-daily dosing (89.0% vs 7.7%; P < 0.001) and would allow them to achieve better long-term compliance (87.5% vs 8.5%; P < 0.001). Clinical AEs were reported in 30.7% of patients treated with once-weekly alendronate and 30% of patients treated with once-daily alendronate, with no significant differences between treatments. CONCLUSION: When once-weekly alendronate 70 mg was compared with once-daily alendronate 10 mg in this study, 70-mg once-weekly alendronate was the preferred dosing regimen.     

Montelukast for migraine prophylaxis: a randomized, double-blind, placebo-controlled study

OBJECTIVE: To evaluate the efficacy and tolerability of montelukast 20 mg in the prophylactic treatment of migraine. BACKGROUND: A previous small open-label study in migraine patients suggested prophylactic efficacy for montelukast, an antagonist of the cysteinyl leukotriene receptor that is used in the treatment of asthma. We sought to confirm these findings in a randomized controlled trial. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-groups study enrolled adult migraine outpatients who experienced > or =3 and < or =8 migraine attacks per month for the last 6 months. Patients were entered into a 2-month, single-blind, placebo run-in phase. Only patients who experienced > or =3 migraine attacks in the second month were eligible to enter the subsequent 3-month, double-blind treatment phase of the study. The primary efficacy endpoint was the percentage of patients reporting at least a 50% decrease in migraine attack frequency per month during the double-blind treatment period (months 3-5) compared to baseline (run-in month 2). RESULTS: A total of 93 patients were randomized to montelukast 20 mg and 84 patients to placebo at the end of the placebo run-in month 2; 76 patients on montelukast and 72 patients on placebo completed the double-blind treatment period. Over 3 months of treatment, there was no significant difference between the two groups in the percentage of patients who reported at least a 50% decrease in migraine attack frequency per month: 15.4% for montelukast versus 10.3% for placebo (P= .304). In addition, montelukast 20 mg was not significantly superior to placebo on any of the secondary endpoints. There were no differences between treatment groups for adverse events. CONCLUSION: Montelukast 20 mg was well tolerated in migraine patients but was not an effective prophylactic for prevention of migraine.     

服用胶原蛋白肽Peptan对膝骨关节炎患者的影响:随机双盲、安慰剂对照的临床研究

目的采用随机双盲、安慰剂对照的前瞻性研究,评估服用胶原蛋白肽Peptan对中老年女性膝骨关节炎患者的效果。方法 100例膝骨关节炎患者随机分成两组,试验组服用胶原蛋白肽Peptan 8 g/d,安慰剂组服用麦芽糊精8 g/d,连续服用6个月。应用WOMAC评分和Lysholm评分来评估治疗前后骨关节疼痛和功能改善状况。结果 (1)服用6个月Peptan组WOMAC评分(11.33±4.28)明显低于安慰剂组(15.00±3.45,P<0.001);Peptan组Lysholm评分(85.24±8.88)明显高于安慰剂组(79.73±9.62,P<0.001);(2)两组WOMAC评分和Lysholm评分治疗前后的差值具有明显统计学差异(P<0.001);(3)服用6个月Peptan组的临床效果(关节疼痛好转和功能恢复情况)明显优于安慰剂组(P<0.001)。结论口服胶原蛋白肽Peptan能有效地改善中老年膝骨关节炎女性患者的关节功能,缓解疼痛,改善生活质量。     

Combination treatment with ipragliflozin and metformin: a randomized, double-blind, placebo-controlled study in patients with type 2 diabetes mellitus

BackgroundIpragliflozin (ASP1941) is a selective sodium glucose cotransporter 2 inhibitor in clinical development for the treatment of patients with type 2 diabetes mellitus (T2DM).ObjectivesThe primary objective was to evaluate the safety profile and tolerability of ipragliflozin as a glucose-lowering agent in combination with stable metformin therapy in patients with T2DM. A secondary objective was to evaluate the effect of ipragliflozin on the pharmacokinetic (PK) properties of metformin.MethodsThirty-six patients with T2DM stable on metformin therapy (850, 1000, or 1500 mg bid) were randomized in a double-blind manner to receive ipragliflozin (300 mg qd; n = 18) or matching placebo (n = 18) for 14 days. Safety profiles, including monitoring of hypoglycemic events, treatment-emergent adverse events (TEAEs), laboratory measurements, and vital signs were assessed throughout the study. The PK properties of metformin and ipragliflozin were determined in plasma. The geometric mean ratio and its 90% CI for the maximum plasma concentration and AUC_0–10 were calculated for metformin + ipragliflozin (day 14) versus metformin alone (day ?1). Pharmacodynamic properties were assessed by measurement of urinary glucose excretion over 24 hours (UGE_0–24).ResultsAll the TEAEs, except 1, were mild. Fifteen TEAEs were observed in the ipragliflozin group (7 of 18 patients [38.9%]), and 19 TEAEs were observed in the placebo group in (8 of 18 patients [44.4%]). Treatment-related TEAEs were reported by 3 of 18 patients (16.7%) receiving metformin + ipragliflozin and by 5 of 18 patients (27.8%) receiving metformin + placebo. No hypoglycemic events (blood glucose level <54 mg/L [to convert to millimoles per liter, multiply by 0.0555]) were observed. The geometric mean ratios for C_max and AUC_0–10 of metformin + ipragliflozin versus metformin alone were 1.11 (90% CI, 1.03–1.19) and 1.18 (90% CI, 1.08–1.28), respectively. After ipragliflozin treatment, UGE_0–24 on day 14 (74.9 g) was significantly higher than that in the placebo group (3.6 g) and at baseline (3.3 g).ConclusionsCombination treatment for 14 days with ipragliflozin and metformin was well tolerated in patients withT2DM without hypoglycemia. The addition of ipragliflozin (300 mg qd) to metformin therapy did not result in a clinically relevant change in the PK properties of metformin. ClinicalTrials.gov identifier: NCT01302145.     

Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study

OBJECTIVE: To assess the efficacy and safety of i.v. haloperidol in treatment of acute migraine headache in a double-blind, randomized, placebo-controlled study design. BACKGROUND: Neuroleptics are mainly used as antiemetics in acute migraine. In a previous open trial haloperidol was effective in relieving migraine pain. DESIGN: Patients were randomized into 2 groups receiving intravenously either 5 mg haloperidol in 500 mL of normal saline or 500 mL of normal saline alone. Pain was assessed by visual analogue scale (VAS) before and 1 to 3 hours after the infusion. If the patient felt no relief in pain intensity 1 to 3 hours after the infusion and had received placebo, he/she then received haloperidol infusion as an open trial. The open trial also included 7 patients who refused from the placebo-controlled trial. About 1 month after the infusion the patients were contacted by telephone and interviewed about the side effects of the treatment. RESULTS: Forty patients were enrolled into the double-blind, placebo-controlled study. Before the infusion the VAS values were 7.7 in the haloperidol and 7.2 in the placebo group. After the infusion the VAS values were 2.2 in the haloperidol and 6.3 in the placebo group (P < .0001). Significant pain relief was achieved in 80% of the patients treated with haloperidol, whereas only 3 patients (15%) responded to placebo (P < .0001). Seventeen patients treated with placebo without response together with 7 patients who refused from the placebo-controlled study participated in the open trial. In this group VAS declined from 6.7 to 2.4 and 79% of these patients felt significant pain relief. The most common side effects caused by haloperidol were sedation and akathisia, the latter being more troublesome. These effects were very common in patients participating in the double-blind (80%) and open (88%) trials. Sixteen percent of the patients considered the side effects intolerable and would not like the migraine attacks to be treated with haloperidol in the future. Three patients (7%) returned to the emergency ward because of a relapse. CONCLUSIONS: This study shows that i.v. haloperidol is very effective in relieving migraine-associated pain. Because the majority of the patients had taken other medication without response, haloperidol appears to be an effective rescue medication even when other types of treatment have failed. Relapses are rare, but side effects are common, limiting the use of haloperidol in some patients.     

Cognitive function improvement with astaxanthin and tocotrienol intake: a randomized,double-blind,placebo-controlled study

We examined the effects of the mixed ingestion of astaxanthin derived from Haematococcus pluvialis and tocotrienols on the cognitive function of healthy Japanese adults who feel a memory decline. Forty-four subjects were randomly but equally assigned to the astaxanthin-tocotrienols or placebo group. An astaxanthin-tocotrienols or placebo capsule was taken once daily before or after breakfast for a 12-week intervention period. The primary outcome was composite memory from the Cognitrax cognitive test, and the secondary outcomes were other cognitive functions and subjective symptoms for memory. Each group included 18 subjects in the efficacy analysis (astaxanthin-tocotrienols group, 55.4 ± 7.9 years; placebo group, 54.6 ± 6.9 years). The astaxanthin-tocotrienols group showed a significant improvement in composite memory and verbal memory in Cognitrax at Δ12 weeks compared with the placebo group. Additionally, the astaxanthin-tocotrienols group showed a significant improvement in the subjective symptom of “During the last week, have you had trouble remembering people’s names or the names of things?” compared with the placebo group after 12 weeks. No adverse events were observed in this study. The results demonstrated that taking an astaxanthin-tocotrienols combination improves the composite memory and verbal memory of Japanese adults who feel a memory decline (UMIN 000031758).     

Smoking reduction treatment with 4-mg nicotine gum: a double-blind, randomized, placebo-controlled study

BACKGROUND: Smoking reduction may provide a harm-reduction alternative treatment for smokers who are not ready to quit smoking. This study evaluated the efficacy of nicotine gum in helping smokers reduce or quit smoking. METHODS: This randomized, double-blind, placebo-controlled trial involved 364 smokers who were not ready to quit but were willing to reduce their smoking intensity. Participants received either 4-mg nicotine gum (n = 184) or placebo gum (n = 180) as desired for up to 12 months. The primary outcome was sustained smoking reduction, which was defined as a decrease in daily cigarette consumption of at least 50% compared with baseline. Secondary measures included point-prevalence abstinence, intention to quit, and cardiovascular risk markers. RESULTS: At 4 months, the sustained smoking reduction rate in the nicotine gum group was twice that of the placebo group (15.8% versus 6.7%, P = .008). Point-prevalence abstinence was 6.6% for the nicotine gum group and 2.2% for the placebo group (P = .07). At 13 months, there was a significant difference in the smoking reduction rate for the nicotine (8.2%) and placebo (2.8%) groups (P = .036). At month 13, the abstinence rates were 12% and 4.5% for the nicotine and placebo groups, respectively (P = .012). Concomitant use of nicotine gum and cigarette smoking was well tolerated. Carbon monoxide levels decreased significantly (P = .01). CONCLUSION: Nicotine gum may be an efficacious harm-reduction alternative for smokers who are not ready to quit and may promote smoking cessation, the ultimate goal in the treatment of tobacco dependence.     

Histamine as a therapeutic alternative in migraine prophylaxis: a randomized, placebo-controlled, double-blind study

This study was undertaken to test the efficacy of the subcutaneous administration (twice a week) of consecutively increasing doses of histamine (0.1 to 1 ng) in the prophylaxis of migraine, compared to placebo, under a controlled, double-blind, clinical trial for 12 weeks. Sixty patients were selected, under criteria established by the International Headache Society (both sexes, 18 to 65 years of age, a migraine history of more than 1 year, one to six headache attacks per month), having no additional neurological or cardiovascular pathologies, and after a complete clinical and laboratory examination including computer-assisted tomography. Comparison between the groups treated with placebo (n = 30) and histamine (n = 30), on data collected for the 4th, 8th, and 12th weeks of treatment, revealed that histamine exerted a significantly (P < .0001) greater reduction (compared to placebo) in the frequency, intensity, and duration of migraine attacks, as well as on the use of rescue medication. No significant (P > .05) adverse experiences or side effects in either group developed to impede the blinding of the study or the planned order of events. We conclude that the subcutaneous administration of histamine (at very low doses) constitutes a novel and effective therapeutic approach in migraine prophylaxis, aimed at limiting excessive inflammatory responses involved in the pathophysiology of migraine through the activation of H3 receptors.     

Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study

The aim of this study was to evaluate the efficacy and tolerability of topiramate for the prevention of chronic migraine in a randomized, double-blind, placebo-controlled trial. Chronic migraine is a common form of disabling headache presenting in headache subspecialty practice. Preventive treatments are essential for chronic migraine management, although there are few or no controlled empirical trial data on their use in this patient population. Topiramate is approved for the prophylaxis of migraine headache in adults. Patients (18-65 years) who experienced chronic migraine (defined as > or =15 monthly migraine days) for > or =3 months prior to trial entry and had > or =12 migraine days during the 4-week (28-day) baseline phase were randomized to topiramate or placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly) to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200 mg/day, according to patient need. Existing migraine preventive treatments, except for antiepileptic drugs, were continued throughout the trial. The primary efficacy measure was the change in number of migraine days from the 28-day baseline phase to the last 28 days of the double-blind phase in the intent-to-treat population, which consisted of all patients who received at least one dose of study medication and had one outcome assessment during the double-blind phase. Health-related quality of life was evaluated with the Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1), the Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires, and tolerability was assessed by adverse event (AE) reports and early trial discontinuations. Eighty-two patients were screened. Thirty-two patients in the intent-to-treat population (mean age 46 years; 75% female) received topiramate (mean modal dose +/- SD = 100 +/- 17 mg/day) and 27 patients received placebo. Mean (+/-SD) baseline number of migraine days per 4 weeks was 15.5 +/- 4.6 in the topiramate group and 16.4 +/- 4.4 in the placebo group. Most patients (78%) met the definition for acute medication overuse at baseline. The mean duration of treatment was 100 and 92 days for topiramate- and placebo-treated patients, respectively. Study completion rates for topiramate- and placebo-treated patients were 75% and 52%, respectively. Topiramate significantly reduced the mean number of monthly migraine days (+/-SD) by 3.5 +/- 6.3, compared with placebo (-0.2 +/- 4.7, P < 0.05). No significant intergroup differences were found for MSQ and HIT-6. MIDAS showed improvement with the topiramate treatment group (P = 0.042 vs. placebo). Treatment emergent adverse events were reported by 75% of topiramate-treated patients (37%, placebo). The most common AEs, paraesthesia, nausea, dizziness, dyspepsia, fatigue, anorexia and disturbance in attention, were reported by 53%, 9%, 6%, 6%, 6%, 6% and 6% of topiramate-treated patients, respectively, vs. 7%, 0%, 0%, 0%, 0%, 4% and 4% of placebo-treated patients. This randomized, double-blind, placebo-controlled trial demonstrates that topiramate is effective and reasonably well tolerated when used for the preventive treatment of chronic migraine, even in the presence of medication overuse.     

A dose-ranging study of midazolam for postoperative sedation of patients: a randomized,double-blind,placebo-controlled trial

OBJECTIVE: To evaluate the dose range, efficacy, and safety of midazolam for induction of sedation of mechanically ventilated postoperative patients in the intensive care unit. DESIGN: A randomized, double-blind, placebo-controlled study. SETTING: Thirteen intensive care units in Japan. PATIENTS: We included 98 patients undergoing general surgery who were ASA physical status I-III. The following inclusion criteria were applied to the patients after surgery: under mechanical ventilation, sedation level 2 or 3 on the Ramsay Sedation Scale, and any pain level but 4 on the Pybus and Torda Pain Scale. MEASUREMENTS AND RESULTS: Of the 98 patients initially enrolled in the study, 95 patients received one of the study medications: placebo (n = 24), 0.015 mg/kg midazolam (n = 21), 0.03 mg/kg midazolam (n = 26), or 0.06 mg/kg midazolam (n = 24). Level of sedation was assessed by using the Ramsay Sedation Scale before and 10 mins after medication. The proportions of patients with sedation level 4 or deeper after medication were 4.3%, 14.3%, 52.0%, and 90.9% in the placebo and the midazolam 0.015 mg/kg, 0.03 mg/kg, and 0.06 mg/kg groups, respectively. Safety was assessed by routine monitoring of body functions and monitoring for adverse events. Although midazolam dose-dependently reduced mean systolic arterial pressure, the changes in this variable were small; only one or two patients in each treatment group had decreases in systolic arterial pressure of >20%. No clear dose dependency was found for changes in other body functions measured in the intensive care unit. CONCLUSION: The proportion of patients who achieved a satisfactory level of sedation increased with an increasing dose of midazolam. Intravenous bolus injection of midazolam also dose-dependently reduced mean systolic arterial pressure. This study indicated that, balancing sedative efficacy and safety, from 0.03 to 0.06 mg/kg of midazolam provides relatively safe sedation in postoperative patients.     

Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen

The effective treatment of patients suffering from central neuropathic pain remains a clinical challenge, despite a standard pharmacological approach in combination with anticonvulsants and antidepressants. A randomized, double-blinded, placebo-controlled trial evaluated the effects of pregabalin on pain relief, tolerability, health status, and quality of life in patients with central neuropathic pain caused by brain or spinal cord injuries. At baseline and 4 weeks after the start of treatment subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analog scale, health status (Pain Disability Index and EQ-5D) and quality of life (SF-36). Forty patients received escalating doses of either pregabalin (150, 300, and 600 mg/day) or matching placebo capsules. In both groups, patients started with 1 capsule per day (either 150 mg of pregabalin or placebo). If pain relief was insufficient, patients were titrated to a higher dose. There was a statistically significant decrease in mean pain score at endpoint for pregabalin treatment, compared with placebo (P = 0.016). Follow-up observation showed no significant difference in Pain Disability Index scores between the two groups. The pregabalin group, however, showed a statistically significant improvement for the EQ-5D. Pregabalin treatment led to a significant improvement in the bodily pain domain of the SF36. In the other domains, more favorable scores were reported without reaching statistical significance. Pregabalin, in a flexible-dose regime, produced clinically significant reductions in pain, as well as improvements in health status in patients suffering from severe central neuropathic pain.     

Sumatriptan nasal spray in adolescent migraineurs: a randomized, double-blind, placebo-controlled, acute study

OBJECTIVE: To compare the efficacy and tolerability of sumatriptan nasal spray (NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subjects. BACKGROUND: Currently, no triptan is approved in the United States for the treatment of migraine in adolescent subjects (12 to 17 years). In a previous randomized, placebo-controlled study of 510 adolescent subjects, sumatriptan NS at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy analysis for headache relief with 20 mg at 2 hours did not demonstrate statistical significance (P = .059). A second study was initiated to evaluate the efficacy of sumatriptan NS in this population. METHODS: This was a randomized (1:1:1), placebo-controlled, double-blind, parallel-group study. Overall, 738 adolescent subjects (mean age: 14 years) with > or = 6-month history of migraine (with or without aura) self-treated a single attack of moderate or severe migraine. The primary endpoints were headache relief at 1 hour and sustained relief from 1 to 24 hours. Pain-free rates, presence/absence of associated symptoms, headache recurrence, and use of rescue medications were also assessed. Tolerability was based on adverse events (AEs) and vital signs. RESULTS: Sumatriptan NS 20 mg provided greater headache relief than placebo at 30 minutes (42% vs. 33%, respectively; P = .046) and 2 hours (68% vs. 58%; P = .025) postdose, but did not reach statistical significance at 1 hour (61% vs. 52%; P = .087) or for sustained headache relief from 1 to 24 hours (P = .061). Significant differences (P < .05) in favor of sumatriptan NS 20 mg over placebo were observed for several secondary efficacy endpoints including sustained relief from 2 to 24 hours. In general, sumatriptan NS 5 mg percentages were slightly higher than placebo but the differences did not reach statistical significance. Both doses of sumatriptan NS were well tolerated. No AEs were serious or led to study withdrawal. The most common event was taste disturbance (2%, placebo; 19%, sumatriptan NS 5 mg; 25%, sumatriptan NS 20 mg). CONCLUSIONS: This study suggests that sumatriptan may be beneficial to some adolescents and is generally well tolerated in the acute treatment of migraine in this population.     

Divalproex extended-release in adolescent migraine prophylaxis: results of a randomized, double-blind, placebo-controlled study

Objective.— To evaluate the efficacy, tolerability, and safety of 3 different doses of divalproex sodium extended‐release vs placebo in the prophylaxis of migraine headaches in adolescents. Background.— Divalproex sodium has been approved for migraine prophylaxis in adults, and previous uncontrolled data suggest divalproex sodium may be effective in preventing migraine in children and adolescents with acceptable tolerability. Methods.— This was a 12‐week, phase 3, randomized, placebo‐controlled, double‐blind, parallel‐group, multicenter study in approximately 300 adolescents aged 12 to 17 years with migraine headaches. At the end of the baseline phase, subjects still meeting study criteria were randomized in a 1 : 1 : 1 : 1 ratio to receive divalproex sodium extended‐release 250 mg, 500 mg, or 1000 mg once daily, or placebo. The primary efficacy variable was reduction from baseline in 4‐week migraine headache rate for each active treatment group vs placebo. Standard safety assessments were conducted and testosterone and sex hormone‐binding globulin levels were collected for postmenarchal females. Results.— There was no statistically significant treatment difference between any divalproex sodium extended‐release dose group and placebo for the primary efficacy variable, reduction from baseline in 4‐week migraine headache rate. There were no statistically significant differences in adverse events between any active treatment group and placebo. A notable dose‐related decrease in platelets was observed, and individuals in all 4 treatment groups had increases in ammonia levels; treatment differences in other laboratory variables were generally small. Among postmenarchal female subjects who were not taking hormonal contraceptives or other steroids, there was no statistically significant change in testosterone levels, but a statistically significant dose‐related increase in sex hormone‐binding globulin was observed. Conclusions.— In the current study, divalproex sodium extended‐release did not differentiate from placebo in the prophylactic treatment of migraine headaches but was generally well‐tolerated in adolescents aged 12 to 17 years.     

Tramadol in post-herpetic neuralgia: a randomized,double-blind,placebo-controlled trial

The efficacy and safety of sustained-release tramadol compared to placebo in the treatment of post-herpetic neuralgia were evaluated in a multicenter, randomized, double-blind, parallel-group study in 127 outpatients. Treatment was administrated for 6 weeks. The dose of tramadol could be increased from 100 mg/day to 400 mg/day (300 mg/day in patients more than 75 years old). Groups were compared on changes in pain intensity on a Visual Analogue Scale (VAS) between inclusion and the 6th week of treatment (covariance analysis as main analysis and repeated measures analysis as complementary analysis) in the per protocol (PP) population. The randomized population comprised 127 patients aged 35-85 years, mostly females (72.4%). Groups were comparable at inclusion both in the intent to treat (ITT) population (63 patients in the tramadol group and 62 patients in the placebo group) and in the PP population (53 patients in the tramadol group and 55 patients in the placebo group). Mean pain intensity on day 43 adjusted on day 1 (covariance analysis) was significantly lower in the tramadol group than in the placebo group in both the PP (P=0.0499), and the ITT (P=0.031) populations. The two groups significantly differed on change in pain intensity over time (repeated measures analysis) in the ITT population (P=0.012). The percentage of pain relief over the 6th week was significantly higher in the tramadol group than in the placebo group (P=0.017). During the 6th week, patients in the tramadol group required less rescue medication than patients in the placebo group (P=0.022). No significant difference was found between groups either in pain intensity on a 5-point Verbal Scale (VRS) or in quality of life measurements. Tramadol was administered at an average dosage of 275.5 (89.7) mg/day after a 1-week dose-adaptation period. Tramadol was well tolerated. No notable difference appeared between groups either in the percentage of patients with treatment-associated adverse events (TAAE) (29.7% in the tramadol group and 31.8% in the placebo group) or in the total number of TAAE (31 in the tramadol group and 28 in the placebo group).