***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In a double blind cross-over study , 28 patients , 5 male and 23 female , aged 31 + /- 14 years , after a run-in period of 8 weeks , were treated for 3 months with acetylsalicylic acid and for another 3 months with metoprolol , both in a prophylactic mode . Attack frequency was reduced significantly with both therapeutic regimens ( ASA p less than 0.001 , metoprolol p less than 0.00005 ) . Reduction of attacks below 50 % was seen with metoprolol in 14 cases , and with ASA in three cases . Even though ASA was of statistically significant efficacy in migraine prophylaxis , it clearly is not the drug of first choice in migraine prophylaxis In the present double-blind clinical trial an isoergolenyl derivative with periphal antiserotonin , central dopaminergic activity and a-increasing effect on the human EEG , lisuride hydrogen maleate , was tested against placebo in a six-month trial involving 240 patients .  Lisuride in long-term administration significantly reduces the frequency of migraine attacks in comparison to placebo . Its advantages are good tolerance and minimal side-effects . It is therefore concluded that lisuride is a suitable and effective drug for the prevention of migraine Metoprolol slow-release tablets ( Durules ® ) , 200 mg , given once daily in the morning were compared with placebo in the prophylaxis of classic migraine . The trial comprised eight Sc and inavian neurologic centres and was design ed as a double-blind cross-over study with 4 weeks ' run-in , four weeks washout , and 8 weeks of either treatment . Seventy-seven patients with two to eight migraine attacks per month were entered in the trial , and 73 completed it . A total of 1119 attacks with aura symptoms and 374 without were recorded . Metoprolol was significantly better than placebo with regard to the total frequency of attacks ( 1.8 versus 2.5 attacks/4 weeks ) , mean duration of attacks ( 6.0 versus 8.0 h/attack ) , mean global rating , and consumption of analgesics per attack : Similar differences could be shown for attacks with aura symptoms alone , except for the duration of attacks .  Metoprolol is the first drug for which a prophylactic effect in classic migraine has been convincingly demonstrated Abstract  Variability  in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Rizatriptan is a potent , oral , 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan . It was postulated that this would result in more rapid onset of effect . This r and omized , double-blind , triple-dummy , parallel-groups study compared rizatriptan 5 mg , rizatriptan 10 mg , sumatriptan 100 mg , and placebo in 1268 out patients treating a single migraine attack .  Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours , with significance at 1 hour ( 37 % versus 28 % , P = 0.010 ) . All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours ( P < or = 0.001 ) . The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that , after adjustment for age imbalance , rizatriptan 10 mg had earlier onset than sumatriptan 100 mg ( P = 0.032 ; hazard ratio 1.21 ) . Rizatriptan 10 mg was also superior to sumatriptan on pain-free response ( P = 0.032 ) , reduction in functional disability ( P = 0.015 ) , and relief of nausea at 2 hours ( P = 0.010 ) . Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg ( 33 % , P = 0.014 ) compared with sumatriptan 100 mg ( 41 % ) . We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg We included 43 patients with migraine without aura in a triple-blind , placebo- and dose-controlled , crossover study of the prophylactic effect of slow-release sodium valproate ; 34 patients completed the trial . The number of days with migraine was 3.5 per 4 weeks during treatment with sodium valproate and 6.1 during placebo ( p = 0.002 ) . The severity and duration of the migraine attacks that did occur were not affected by sodium valproate when compared with placebo . Fifty percent of the patients were responders , ie , their initial migraine frequency was reduced to 50 % or less during sodium valproate as compared with 18 % during placebo . The number of responders increased during the trial to 65 % in the last 4 weeks of the active treatment period . There were no serious side effects requiring withdrawal of patients from the study . We conclude that sodium valproate is an effective and well-tolerated prophylactic medication for migraine without aura CONTEXT Small open-label and controlled trials suggest that the antiepileptic drug topiramate is effective for  migraine prevention  . OBJECTIVE To assess the efficacy and safety of topiramate for migraine prevention in a large controlled trial . DESIGN , SETTING , AND PATIENTS A 26-week , r and omized , double-blind , placebo-controlled study was conducted during outpatient treatment at 52 North American clinical centers . Patients were aged 12 to 65 years and had a 6-month history of migraine ( International Headache Society criteria ) and 3 to 12 migraines a month but no more than 15 headache days a month during a 28-day prospect i ve baseline phase . INTERVENTIONS After a washout period , patients meeting entry criteria were r and omized to topiramate ( 50 , 100 , or 200 mg/d ) or placebo . Topiramate was titrated by 25 mg/wk for 8 weeks to the assigned or maximum tolerated dose , whichever was less . Patients continued receiving that dose for 18 weeks . MAIN OUTCOME MEASURES The primary efficacy measure was change from baseline in mean monthly migraine frequency . Secondary efficacy measures included responder rate ( proportion of patients with > or = 50 % reduction in monthly migraine frequency ) , reductions in mean number of monthly migraine days , severity , duration , and days a month requiring rescue medication , and adverse events . The month of onset of preventive treatment action was assessed . RESULTS Of 483 patients r and omized , 468 provided at least 1 postbaseline efficacy assessment and comprised the intent-to-treat population . Mean monthly migraine frequency decreased significantly for patients receiving topiramate at 100 mg/d ( -2.1 , P = .008 ) and topiramate at 200 mg/d ( -2.4 , P<.001 ) vs placebo ( -1.1 ) . Statistically significant reductions ( P<.05 ) occurred within the first month with topiramate at 100 and 200 mg/d . The responder rate was significantly greater with topiramate at 50 mg/d ( 39 % , P = .01 ) , 100 mg/d ( 49 % , P<.001 ) , and 200 mg/d ( 47 % , P<.001 ) vs placebo ( 23 % ) . Reductions in migraine days were significant for the 100-mg/d ( P = .003 ) and 200-mg/d ( P<.001 ) topiramate groups . Rescue medication use was reduced in the 100-mg/d ( P = .01 ) and 200-mg/d ( P = .005 ) topiramate groups . Adverse events result ing in discontinuation in the topiramate groups included paresthesia , fatigue , and nausea . CONCLUSION Topiramate showed significant efficacy in migraine prevention within the first month of treatment , an effect maintained for the duration of the double-blind phase BACKGROUND Open-label trials and small controlled studies report topiramate 's efficacy in migraine prevention . OBJECTIVE To assess the efficacy and safety of topiramate as a migraine-preventive therapy . DESIGN A 26-week , r and omized , double-blind , placebo-controlled study . SETTING Outpatient treatment at 49 US clinical centers . Patients Patients were aged 12 to 65 years , had a 6-month International Headache Society migraine history , and experienced 3 to 12 migraines per month , but had 15 or fewer headache days per month during the 28-day baseline period . INTERVENTIONS Participants were r and omized to placebo or topiramate , 50 , 100 , or 200 mg/d , titrated by 25 mg/wk to the assigned dose or as tolerated in 8 weeks ; maintenance therapy continued for 18 weeks . MAIN OUTCOME MEASURES The primary efficacy assessment was a reduction in mean monthly migraine frequency across the 6-month treatment phase . Secondary end points were responder rate , time to onset of action , mean change in migraine days per month , and mean change in rescue medication days per month . RESULTS Four hundred eighty-seven patients were r and omized , and 469 composed the intent-to-treat population . The mean + /- SD monthly migraine frequency decreased significantly for the 100-mg/d group ( from 5.4 + /- 2.2 to 3.3 + /- 2.9 ; P < .001 ) and the 200-mg/d group ( from 5.6 + /- 2.6 to 3.3 + /- 2.9 ; P < .001 ) vs the placebo group ( from 5.6 + /- 2.3 to 4.6 + /- 3.0 ) ; improvements occurred within the first treatment month . Significantly more topiramate-treated patients ( 50 mg/d , 35.9 % [ P = .04 ] ; 100 mg/d , 54.0 % [ P < .001 ] ; and 200 mg/d , 52.3 % [ P < .001 ] ) exhibited a 50 % or more reduction in monthly migraine frequency than placebo-treated patients ( 22.6 % ) . Adverse events included paresthesia , fatigue , nausea , anorexia , and taste per version . CONCLUSION Topiramate , 100 or 200 mg/d , was effective as a preventive therapy for patients with migraine OBJECTIVE To confirm the efficacy advantage of eletriptan 40 mg over sumatriptan 100 mg . Background .-Eletriptan 80 mg has demonstrated significantly greater efficacy when compared to both sumatriptan 50 mg and 100 mg in two studies . Eletriptan 40 mg demonstrated significantly greater efficacy than sumatriptan 100 mg in one previous trial . METHODS Two thous and one hundred thirteen patients with a diagnosis of migraine according to International Headache Society criteria were r and omized using a double-blind , double-dummy , parallel-group design , and treated for a single migraine attack with either eletriptan 40 mg , sumatriptan 100 mg , or placebo . The primary endpoint was 2-hour headache response . Secondary endpoints included headache response rates at 1 hour , pain-free rates , absence of associated symptoms 
    Output:
    
Results are generally the same in the meta- analysis and in the comparative trials , with some exceptions .