Eletriptan for the acute treatment of migraine: results of bridging a Japanese study to Western clinical trials

SUMMARY

Objective: To compare the efficacy, safety and tolerability of eletriptan (20,40 and 80?mg) to placebo when given to Japanese and Western patients for the acute treatment of migraine.

Methods: A double-blind, randomized, parallel-group trial with the aforementioned therapeutic objectives was conducted in Japan (N?=?321). By bridging analysis, data from this study were compared to two migraine trials previously conducted in the US (N?=?1190) and Europe (N?=?563).

Results: The 2-h post-dose headache response rates (i.e., the primary efficacy endpoint) of Japanese migraineursto eletriptan 20, 40 and 80?mg were 64, 67 and 76%, respectively; European and American migraineurs showed similar trends and, in these studies, eletriptan was significantly superior to placebo (p <0.05). Japanese patients did demonstrate a higher placebo response than Westerners, possibly due to differences in previous triptan exposure or expectation. Adverse events were generally mild to moderate, were comparable in all three studies, and showed a modest dose-response effect.

Conclusion:The efficacy and tolerability of eletriptan for the acute treatment of migraine is comparable in Japan, Europe and the US.     

The impact of migraine on psychological well-being of young women and their communication with physicians about migraine: a multinational study

ABSTRACT

Objective: To describe the impact of migraine on psychological well-being of young women and to evaluate their communication with physicians about migraine.

Research design and methods: This cross-sectional telephone survey was conducted in Israel and eight European countries (Finland, Germany, Greece, Italy, Norway, Spain, Sweden, and The Netherlands). Random-digit dialing was used to identify eligible study participants: women 18–35 years of age with migraine, who used medication to treat their migraine, and who were employed or full-time students.

Results: Of 1810 participants, 42% self-reported having a physician diagnosis of migraine. Eighty-six per cent believed that their life would be better if they did not suffer from migraines; and 58% of participants felt frustrated, 46% felt angry, and 44% felt depressed because of their migraines. Negative feelings related to migraine varied substantially from country to country. For example, feelings of frustration caused by migraine ranged from 32% in Italy to 84% in Finland; feelings of anxiety ranged from 21% in Norway to 57% in Italy; and feelings of confusion ranged from 13% in Greece to 61% in Italy. Overall, 81% of participants had visited a physician in the past year but only 50% of them had discussed their severe headaches or migraines with their physician within the year. While 68% of those who had visited a physician stated that they were comfortable speaking with their physician about migraine, 71% reported being the one who initiated the conversation about severe headaches or migraines. Of all participants, 39% did not feel that their physician understood how much severe headaches or migraines interfered with their life.

Conclusions: Migraines and severe headaches impose a substantial burden on the psychological well-being of young women with migraine in Europe and Israel. In general, communication between these women and their physicians about migraine is incomplete.     

A randomized,double-blinded,placebo-controlled,parallel trial of vitamin D3 supplementation in adult patients with migraine

Background: Vitamin D levels have been linked to certain pain states, including migraine. This study investigated whether vitamin D supplementation would be beneficial for adult patients with migraine (ClinicalTrials.gov Identifier: NCT01695460).

Methods: A randomized, double-blinded, placebo-controlled parallel trial was conducted in migraine patients (36 women and 12 men, 18–65 years of age). A 4-week baseline period was conducted before randomization to 24 weeks of treatment. Participants were assigned to receive D3-Vitamin (n?=?24, 18 women and 6 men, 100?μg/day D3-Vitamin) or placebo (n?=?24,?18 women and 6 men). Migraine attacks and related symptoms were assessed by self-reported diaries. The response rate (i.e. experiencing a 50% or greater reduction in migraine frequency from baseline to week 24), change in migraine severity, and number of migraine days were recorded. Changes in migraine-related symptoms, HIT-6^TM scores, and pain sensitivity tests (pressure pain threshold and temporal summation) were also evaluated. Serum levels of both 25 (OH)D and 1,25 (OH)₂D were assessed from baseline to week 24.

Results: The number of headache days changed from 6.14?±?3.60 in the treatment group and 5.72?±?4.52 in the placebo group at baseline to 3.28?±?3.24 and 4.93?±?3.24 by the end of the trial, respectively. Migraine patients on D3-Vitamin demonstrated a significant decrease (p?<?.001) in migraine frequency from baseline to week 24 compared with placebo. However, migraine severity, pressure pain thresholds, or temporal summation did not show a significant change. 25(OH)D levels increased significantly for the D3-Vitamin group during the first 12 weeks of treatment. There was no significant change in 1,25(OH)₂D. No side-effects were reported or noted.

Conclusions: D3-Vitamin was superior to placebo in reducing migraine days in migraine patients. Larger studies are required to confirm that vitamin D₃ might be one of the prophylactic options for adult patients with migraine.     

Randomized,placebo-controlled comparison of early use of frovatriptan in a migraine attack versus dosing after the headache has become moderate or severe

SUMMARY

Objective: To evaluate whether frovatriptan would provide greater relief if given early during a migraine attack.

Research design and methods: Adults with a history of migraine of at least 1?year, and who had 2–8 headaches in the previous month were recruited from 19 US centres for a prospective, placebo-controlled crossover study over 2 migraine attacks. Dose 1 was taken at the onset of mild migraine headache, Dose 2 was taken at least 2?h later if the headache progressed to moderate/severe. Patients were randomized to receive Dose 1 frovatriptan then Dose 2 placebo or Dose 1 placebo followed by Dose 2 frovatriptan. Treatment order was reversed for the second attack. This schedule enabled a comparison of frovatriptan with placebo and a comparison of early and later treatment with frovatriptan.

Main outcome measures: Freedom from pain at 2?h for frovatriptan versus placebo as Dose 1; use of Dose 2 and/or rescue medication, pain severity, functional impairment and headache recurrence.

Results: In 241 patients who each treated 2 migraine attacks, Dose 1 frovatriptan was more effective than placebo in terms of the proportion of patients who were pain free at 2?h (28% vs 20%, p = 0.04). This benefit was sustained up to 4?h post-dose (?p = 0.003). Early use of frovatriptan significantly reduced re-medication (?p < 0.001). Twenty-four-hour headache recurrence was low in both early (4%) and later use (6%) groups. Sustained pain-free response occurred in 40% of frovatriptan early use patients compared with 31% of later use patients (?p < 0.05). Early use prevented headache progression: 69%–78% had mild/no headache 2–4?h after Dose 1 frovatriptan compared with 54%–63% taking Dose 1 placebo (?p < 0.001). Early use reduced pain burden and functional disability (?p ≤ 0.001). More patients rated early use of frovatriptan as excellent or good (57% vs 46%).

Conclusions: Early use of frovatriptan resulted in a higher, earlier and sustained pain-free response, prevented progression to moderate/severe headache and reduced pain burden and functional disability.     

Postmarketing migraine survey of frovatriptan: effectiveness and tolerability vs previous triptans,NSAIDs or a combination

Abstract

Objective:

Compare the effectiveness and tolerability of current therapy with frovatriptan 2.5-mg tablets (in 1–3 migraines) in patients with migraine previously using other triptans, analgesics/nonsteroidal anti-inflammatory drugs (NSAIDs), or triptans and NSAIDs (T+NSAIDs).     

The impact of migraine on work,family, and leisure among young women – a multinational study

SUMMARY

Objective: To assess the impact of migraine on work, family, and leisure among young women who were employed full or part time, or as a full-time student.

Research design and methods: This cross-sectional telephone survey with 6-month recall was conducted in Israel and eight European countries (Finland, Germany, Greece, Italy, Norway, Spain, Sweden, and The Netherlands). Random-digit dialing was used to identify study participants: women 18–35 years of age with migraine, who used medication to treat their migraine, and who were employed or full-time students.

Results: Of 1810 participants, 42% self-reported having a physician diagnosis of migraine. During the prior 6 months, 46% of participants missed at least 1 day of work or school and 74% were prevented from functioning fully at work or school because of migraine. Mean work/school absenteeism due to migraine was 1.9 days over 6 months (range, 0.8 days in Sweden to 2.8 days in Norway). Over half of participants reported one or more occurrences of being unable to spend time with family or friends (62%) or being unable to enjoy recreational or leisure activities (67%) because of migraine. The percentage of study participants using triptans was lowest in southern Europe and highest in the Nordic countries, ranging from 1% in Greece to 50% in Sweden. Country, age, marital status, physician diagnosis of migraine, and number of migraines or severe headaches in the prior year were independent predictors of the mean number of days of migraine-related work loss. Migraine-related work loss was lowest in Sweden and greatest in Greece, Israel, and The Netherlands. Higher work loss was recorded for those 18–24 years of age; those who were separated, widowed, or divorced; those with migraine diagnosed by a physician; and those with more frequent migraines or severe headaches (≥ 24/year). The 6-month recall period used when estimating patient-reported work loss, and identifying participants with migraine based on self-reported migraine or severe headache, were the most important limitations of the study.

Conclusions: We found substantial migraine-related impairment of productivity at work and school as well as of family and leisure time among young women in Israel and eight European countries.     

加巴喷丁治疗偏头痛的有效性和安全性——随机、双盲对照研究

目的：评价加巴喷丁治疗偏头痛的有效性及安全性。方法：采用随机、双盲、安慰剂平行对照研究,为期8周,共有104例偏头痛患者（年龄18～60岁）被随机分至治疗组和对照组。治疗组：55例,接受加巴喷丁治疗4周;对照组：49例,口服安慰剂4周。在开始治疗时及治疗后4周、8周时采用数字评价量表对患者的疼痛程度进行评估,同时监测患者的肝肾功能、经颅多普勒超声（TCD）、脑电图（EEG）及药物不良反应。结果：4周后加巴喷丁治疗组患者头痛发生率（次/月）、持续时间（h）、疼痛程度（分）均明显下降,分别由6.4±2.5降至2.3±1.5、21.8±12.6下降至8.6±4.3、8.6±1.2降至2.4±1.1。与对照组比较,差异有统计学意义（P〈0.01）。而不良反应轻微,其发生率与对照组比较差异无统计学意义（P〉0.05）。结论：加巴喷丁能有效降低偏头痛的发作次数、疼痛程度及疼痛持续时间,而不良反应轻微,安生性较高。     

Oral zolmitriptan in the short-term prevention of menstrual migraine: a randomized, placebo-controlled study

OBJECTIVE: To evaluate the efficacy and tolerability of oral zolmitriptan as a short-term preventative therapy for menstrual migraine. METHODS: This was a randomized, double-blind, parallel group, placebo-controlled, multicentre, two-phase study. The results of the second phase are reported here (the first phase evaluated zolmitriptan in the acute treatment of menstrual migraine and is reported elsewhere). Women who successfully completed phase I (with either a positive or negative outcome, and who still fulfilled the inclusion criteria) were randomized to zolmitriptan 2.5 mg oral tablet three times daily, zolmitriptan 2.5 mg twice daily or placebo three times daily. Patients were treated for three consecutive menstrual cycles, starting 2 days prior to the expected onset of menses, for 7 days in total. RESULTS: Two hundred and fifty-three patients completed phase I and were eligible for phase II. The intention-to-treat population comprised 244 patients (zolmitriptan three times daily [n = 83]; zolmitriptan twice daily [n = 80]; placebo [n = 81]). Both zolmitriptan regimens demonstrated superior efficacy versus placebo, as measured by the proportion of patients with a >/=50% reduction in the frequency of menstrual migraine attacks (zolmitriptan three times daily [58.6%], p = 0.0007 vs placebo; zolmitriptan twice daily [54.7%], p = 0.002 vs placebo; placebo three times daily [37.8%]). The mean frequency of breakthrough migraine attacks per menstrual cycle was reduced accordingly. Fewer breakthrough attacks were treated with escape medication in the zolmitriptan three times daily (61.6% of attacks; p = 0.0004 vs placebo) and twice daily (60.7%; p = 0.0055 vs placebo) treatment groups than in the placebo group (74.4%). Short-term preventative therapy with zolmitriptan was well tolerated. CONCLUSION: Zolmitriptan 2.5 mg oral tablet is effective and well tolerated as a short-term preventative therapy for menstrual migraine attacks.     

针刺治疗偏头痛的系统评价和Meta分析

目的:应用Meta分析方法,系统评价针刺治疗偏头痛的疗效和分析国内外评价疗效差异的原因。方法:检索Pubmed、Cochrane Library、中国生物医学文献数据库(CBM)等数据库,筛选针刺治疗偏头痛的随机对照临床试验(randomized controlled trials,RCT),应用Cochrane协作网提供的Rev Man 5.0软件进行统计分析。结果:本研究共纳入12篇高质量的、以假针刺组为对照的RCT。Meta分析结果显示:针刺治疗结束时,真针刺和假针刺组的有效率分别为49.5%和43.3%,两组之间有统计学差异(OR=1.28,95%CI:1.02~1.61,P=0.03);随访结束时,两组的有效率分别为47.7%和38.5%,两组间无统计学差异(OR=1.33,95%CI:0.70~2.51,P=0.39)。对国内及国外临床试验进行亚组分析发现,在治疗结束及随访结束时,国内试验针刺组的有效率均显著高于假针刺组(P<0.05),而国外临床试验均显示两组间无统计学意义(P>0.05)。结论:上述结果提示在治疗期间针刺对偏头痛具有一定疗效,但治疗停止的随访期间针刺的疗效不显著。国内外临床试验在设计及执行等方面差异较大,今后尚需更多科学严谨的、符合中医特点的高质量RCT来验证针刺治疗偏头痛的疗效。     

Aripiprazole for the treatment of psychosis in patients with Alzheimer's disease: a randomized, placebo-controlled study

This study compared the efficacy, safety, and tolerability of aripiprazole, a novel antipsychotic, with placebo in patients with psychosis associated with Alzheimer's Disease (AD). This 10-week, double-blind, multicenter study randomized 208 outpatients (mean age, 81.5 years) with AD-associated psychosis to aripiprazole (n = 106) or placebo (n = 102). The initial aripiprazole dose of 2 mg/d was titrated upwards (5, 10, or 15 mg/d) according to efficacy and tolerability. Evaluations included Neuropsychiatric Inventory (NPI) Psychosis subscale and Brief Psychiatric Rating Scale (BPRS), adverse event (AE) reports, extrapyramidal symptoms (EPS) rating scales, and body weight. Overall, 172 patients (83%) completed the study. Mean aripiprazole dose at end point was 10.0 mg/d. The NPI Psychosis subscale score showed improvements in both groups (aripiprazole, -6.55; placebo, -5.52; P = 0.17 at end point). Aripiprazole-treated patients showed significantly greater improvements from baseline in BPRS Psychosis and BPRS Core subscale scores at end point compared with placebo. AEs were generally mild to moderate in severity and included (aripiprazole vs. placebo): urinary tract infection (8% vs. 12%), accidental injury (8% vs. 5%), somnolence (8% vs. 1%), and bronchitis (6% vs. 3%). Somnolence was mild and not associated with falls or accidental injury. There were no significant differences from placebo in EPS scores, or clinically significant ECG abnormalities, vital signs, or weight. In conclusion, aripiprazole showed similar improvements to placebo in psychotic symptoms as assessed by NPI Psychosis subscale scores, but significantly greater effects on BPRS Core and Psychosis assessments in community-living AD patients with psychosis. Aripiprazole was safe and well tolerated in this patient population.     

Bupropion in the treatment of pathological gambling: a randomized, double-blind, placebo-controlled, flexible-dose study

We tested the efficacy of bupropion in the treatment of persons with pathological gambling (PG). Nondepressed, healthy subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition PG were randomly assigned to placebo or flexibly dosed bupropion in a 12-week double-blind trial. Outcome measures included the Yale-Brown Obsessive-Compulsive Scale modified for PG, the Gambling Severity Assessment Scale, the Clinical Global Impression Improvement and Severity Scales, the Global Assessment Scale, the Timeline Follow Back, the Attention-Deficit/Hyperactivity Disorder Rating Scale, and the Sheehan Disability Scale. Thirty-nine subjects (28 men, 11 women) were randomized to bupropion (n = 18) or placebo (n = 21). The 2 groups were similar on demographic and clinical measures. There were few differences between the treatment groups on any primary or secondary outcome measure, although subjects in each cell experienced significant improvement. Of subjects with at least 1 postrandomization visit, 35.7% of bupropion and 47.1% of placebo recipients experienced "much" or "very much" improvement on the Clinical Global Impression Improvement Scale. The trial was complicated by a high noncompletion rate (43.6%). Bupropion was well tolerated. Bupropion and placebo recipients did equally well in a short-term trial, with improvement seen as early as the first week of treatment. The high placebo response rate and the high noncompletion rate each reflect the challenge inherent in treating persons with PG.     

Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized,double-blind,placebo-controlled trial

Abstract

Objective:

To determine the efficacy, tolerability, and safety of duloxetine when added to oral nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with osteoarthritis (OA) of the knee with pain of moderate or greater severity.     

Lamotrigine treatment of aggression in female borderline-patients: a randomized, double-blind, placebo-controlled study

Anger and aggression are typical in borderline patients. The goal of this study was to compare the efficacy of lamotrigine versus placebo in the treatment of aggression in women meeting the criteria for borderline personality disorder (BPD). We conducted a randomized, double-blind, placebo-controlled study of lamotrigine in 24 female subjects meeting Structured Clinical Interview for DSM-IV (SCID) criteria for BPD. The subjects were randomly assigned in a 2: 1 manner ratio to lamotrigine (n = 18) or placebo (n = 9). Treatment duration was 8 weeks. Primary outcome measures were self-reported changes on the anger scales of the Trait Anger Expression Inventory (STAXI). In comparison with the placebo group, and according to the intention-to-treat principle, highly significant (p < 0.01) changes on four STAXI scales (State-Anger, Trait-Anger, Anger-Out, Anger-Control) were observed in those subjects treated with lamotrigine after 8 weeks. The only exception (p < 0.05) was found on the Anger-In scale, where a difference of only 8.5% (p < 0.2) was found. All the patients tolerated lamotrigine relatively well. Lamotrigine appears to be a safe and effective agent in the treatment of anger in women with criteria-defined BPD as defined by SCID criteria. It did not produce any clinically significant effect on body weight.     

Mirtazapine treatment of social phobia in women: a randomized, double-blind, placebo-controlled study

Social phobia is an anxiety disorder characterized by extreme fear and phobic avoidance of social and performance situations and by a relatively poor health-related quality of life. The goal of this study was to compare the efficacy of mirtazapine versus placebo in the treatment of patients with social phobia. In 2004, we conducted a randomized, double-blind, placebo-controlled study of mirtazapine in 66 female subjects from the general population meeting the criteria for social phobia. The subjects were randomly assigned in a 1:1 manner to mirtazapine (n = 33) or placebo (n = 33). The treatment lasted 10 weeks. Seven patients dropped out. Primary outcome measures were self-reported changes on the Social Phobia Inventory, Liebowitz Social Anxiety Scale, and Health Survey (SF-36). In comparison with the placebo group and according to the intent-to-treat principle, significant differences on the Social Phobia Inventory and Liebowitz Social Anxiety Scale scales (all P < 0.001), as well as on most (5 from 8) scales of SF-36 (all P < 0.001), were observed in the mirtazapine-treated subjects. All patients tolerated mirtazapine relatively well. Mirtazapine appears to be an effective agent in the treatment of social phobia in women and in the improvement of their health-related quality of life.     

Further assessment of the clinically effective dose range of etoricoxib: a randomized,double-blinded,placebo-controlled trial in rheumatoid arthritis

Abstract

Objective:

To further assess the clinically active dose range of etoricoxib, a COX-2 selective inhibitor, in rheumatoid arthritis (RA).     

Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial

Cannabis dependence is a substantial public health problem. Behavioral treatments have shown promise, but there are no effective medications for cannabis dependence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, in treating cannabis dependence. 156 cannabis-dependent adults were enrolled in a randomized, double-blind, placebo-controlled, 12-week trial. After a 1-week placebo lead-in phase, participants were randomized to receive dronabinol 20mg twice a day or placebo. Doses were maintained until the end of week 8 and then tapered off over 2 weeks. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow back method. There was no significant difference between treatment groups in the proportion of participants who achieved 2 weeks of abstinence at the end of the maintenance phase (dronabinol: 17.7%; placebo: 15.6%). Although both groups showed a reduction in marijuana use over time, there were no differences between the groups. Treatment retention was significantly higher at the end of the maintenance phase on dronabinol (77%), compared to placebo (61%) (P=.02), and withdrawal symptoms were significantly lower on dronabinol than placebo (P=.02). This is the first trial using an agonist substitution strategy for treatment of cannabis dependence. Dronabinol showed promise, it was well-tolerated, and improved treatment retention and withdrawal symptoms. Future trials might test higher doses, combinations of dronabinol with other medications with complementary mechanisms, or with more potent behavioral interventions.