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Jes Olesen - One of the best experts on this subject based on the ideXlab platform.
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pre treatment with Sumatriptan for cilostazol induced headache in healthy volunteers
Journal of Headache and Pain, 2018Co-Authors: Katrine Falkenberg, Jes OlesenAbstract:Background Previous studies indicate that Sumatriptan is not effective when second messenger levels are high as after cilostazol provocation. Therefore, we have conducted the present study, where Sumatriptan is administrated as pretreatment before cAMP increases due to cilostazol intake. Our hypothesis was that pretreatment with Sumatriptan would have a significant effect against cilostazol induced headache in healthy volunteers.
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cilostazol induced migraine does not respond to Sumatriptan in a double blind trial
Journal of Headache and Pain, 2018Co-Authors: Katrine Falkenberg, Bara Oladottir A Dunga, Messoud Ashina, Jes OlesenAbstract:Cilostazol is an inhibitor of phosphodiesterase 3 and thus causes accumulation of cAMP. It induces migraine-like attacks in migraine patients. Whether the cilostazol model responds to Sumatriptan in migraine patients and therefore is valid for testing of future anti-migraine medications has never been investigated. In a cross-over study, 30 patients received cilostazol (200 mg p.o.) on two separate days each day followed by oral self-administered placebo or Sumatriptan 50 mg. We recorded headache characteristics and associated symptoms using a questionnaire. The 30 participants were asked to subsequently treat their spontaneous attacks with Sumatriptan (50 mg) or placebo in a double-blind cross-over design and 15 participants did so. Cilostazol induced headache with some migraine characteristics in all participants; 18 patients on the Sumatriptan day and 19 patients on the placebo day fulfilled criteria for a migraine-like attack. The difference in median headache intensity between Sumatriptan and placebo at 2 h was not significant (p = 0.09), but it was at 4 h (p = 0.017). During spontaneous attacks, the difference between placebo and Sumatriptan was not significant at 2 h (p = 0.26), but it was highly significant at 4 h (p = 0.006). The cilostazol model in migraine patients could not be validated by a sufficient Sumatriptan response. The model may perhaps respond to new drugs that act intracellularly or directly on ion channels. The study is registered on clinicaltrials.gov ( NCT02486276 )
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effect of cgrp and Sumatriptan on the bold response in visual cortex
Journal of Headache and Pain, 2012Co-Authors: Mohammad Sohail Asghar, Jes Olesen, Adam E Hansen, Henrik Larsson, Messoud AshinaAbstract:To test the hypothesis that calcitonin gene-related peptide (CGRP) modulates brain activity, we investigated the effect of intravenous CGRP on brain activity in response to a visual stimulus. In addition, we examined if possible alteration in brain activity was reversed by the anti-migraine drug Sumatriptan. Eighteen healthy volunteers were randomly allocated to receive CGRP infusion (1.5 μg/min for 20 min) or placebo. In vivo activity in the visual cortex was recorded before, during and after infusion and after 6 mg subcutaneous Sumatriptan by functional magnetic resonance imaging (3 T). 77% of the participants reported headache after CGRP. We found no changes in brain activity after CGRP (P = 0.12) or after placebo (P = 0.41). Sumatriptan did not affect brain activity after CGRP (P = 0.71) or after placebo (P = 0.98). Systemic CGRP or Sumatriptan has no direct effects on the BOLD activity in visual cortex. This suggests that in healthy volunteers both CGRP and Sumatriptan may exert their actions outside of the blood–brain barrier.
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Sumatriptan has no clinically relevant effect in the treatment of episodic tension type headache
European Journal of Neurology, 1996Co-Authors: Jannick Brennum, T Brinck, L Schriver, B Wanscher, Soelberg P Sorensen, P Tfelthansen, Jes OlesenAbstract:In a randomized, multi-centre, double-blind, placebo-controlled, parallel group study, the efficacy of 100 mg oral Sumatriptan was compared with that of placebo in the treatment of episodic tension-type headache. The patients were recruited from the general population in the vicinity of the study centres, by randomly mailed invitations. One or more attacks were treated with Sumatriptan by 54 patients and with placebo by 57 patients. A seven-point verbal rating scale was used for hourly assessments of headache relief, 1–4 h after treatment According to the predefined primary end-point of the study, which was moderate or complete relief of headache 2 and 4 h after treatment of the first attack, there was no significant difference between Sumatriptan and placebo treatment Sumatriptan did perform statistically significantly better than placebo at some time points, but the effect was not considered clinically relevant We conclude that Sumatriptan should not be used in treatment of tension-type headache. The marked difference in effect of Sumatriptan in treatment of migraine and tension-type headache argues against the idea that migraine and tension-type headache are part of a continuum of headache disorders.
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subcutaneous Sumatriptan during the migraine aura
Neurology, 1994Co-Authors: David W Bates, Aj Pilgrim, E. Ashford, R. Dawson, N. E. Gilhus, Jes Olesen, Fb M Ensink, P ShevlinAbstract:This double-blind, placebo-controlled, multicenter, parallel-group study assessed whether subcutaneous Sumatriptan administered during the migraine aura would prolong or modify the aura and prevent or delay development of the headache. One hundred seventy-one patients (88 receiving 6 mg Sumatriptan, 83 receiving placebo) treated a single attack of migraine with typical aura at home, by self-injection. The median duration of aura following the first injection was 25 minutes for the Sumatriptan group and 30 minutes for the placebo group (NS). The aura symptom profile was similar for the two treatment groups. The proportion of patients who developed a moderate or severe headache within 6 hours after dose administration was similar in the two groups −68% among those receiving Sumatriptan and 75% among those receiving placebo (NS). Sumatriptan given during the aura did not prolong or alter the nature of the migraine aura and did not prevent or significantly delay headache development.
Roger K Cady - One of the best experts on this subject based on the ideXlab platform.
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Sumatriptan: update and review
Expert Opinion on Pharmacotherapy, 2006Co-Authors: Roger K Cady, Curtis P. SchreiberAbstract:Sumatriptan is the first of a novel class of medications referred to as triptans. Since its approval for migraine in the 1990s, six other triptan products have received FDA approval. Despite the proliferation of triptans, Sumatriptan remains the most frequently prescribed product in this therapeutic class. Sumatriptan has been instrumental in defining a biological basis for migraine. It is effective in treating migraine with or without aura, well tolerated and, when properly prescribed, safe. Sumatriptan injection is the only member of the triptan class approved for treatment of cluster headache. Studies with Sumatriptan have also advanced the therapeutic intervention paradigm that permits patients to treat earlier and avoid substantial disability. Numerous pharmacoeconomic studies have demonstrated that Sumatriptan decreases work loss productivity and improves quality of life.
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cost effectiveness and cost benefit of Sumatriptan in patients with migraine
Mayo Clinic Proceedings, 2001Co-Authors: Jennifer H Lofland, Roger K Cady, Alice S Batenhorst, Nelda E Johnson, Mary Lou Chatterton, Robert G Kaniecki, David B NashAbstract:OBJECTIVE: To investigate the cost-effectiveness and cost-benefit of initiating Sumatriptan therapy in patients with acute migraine who were previously taking nontriptan drugs. PATIENTS AND METHODS: This is an economic analysis of a prospective, pretest-posttest, observational 6-month outcomes study of 178 patients with a physician diagnosis of migraine who received their first prescription for Sumatriptan between October 1994 and August 1996 and were members of a mixed-model managed care organization in western Pennsylvania. Migraine-related resource use data were obtained from the managed care organization's medical and pharmacy claims databases. The primary outcome measure for this economic analysis was the total disability time that patients experienced because of migraine. Patients reported time missed from work and usual nonwork activities because of migraine on self-administered questionnaires at baseline and at 3 and 6 months after initiation of Sumatriptan. RESULTS: Initiation of Sumatriptan resulted in a decrease of 662 migraine-disability-days for work and 1236 migraine-disability-days for nonwork activities during the 6 months of the study (decrease from 27.8 to 17.2 days per person), totaling 1898 migraine-disability-days averted with Sumatriptan therapy. Migraine-related medical costs were lower after Sumatriptan was initiated ($18,351 vs $26,192), whereas migraine-related pharmacy costs were lower with prior nontriptan drug therapy ($22,209 vs $74,861). The overall net cost savings after Sumatriptan was initiated in these patients was $222,332 ($1249 per patient) with a benefit-to-cost ratio of $5.67 gained for each health care dollar spent from a societal perspective. The incremental cost-effectiveness ratio was $25 for each additional migraine-disability-day averted by using Sumatriptan vs nontriptan drug therapy. Sensitivity analysis showed that changes in medical costs had little effect on the ratios and that Sumatriptan remained cost-beneficial across a wide range of patient wages. CONCLUSION: This study showed that initiation of Sumatriptan in patients previously receiving nontriptan therapy was cost-effective and had an economic benefit for patients, employers, and society. Sumatriptan also helped patients and physicians achieve goals recommended by the US Headache Consortium by reducing patients' disability and thus improving their ability to function at work and nonwork activities.
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effectiveness of Sumatriptan in reducing productivity loss due to migraine results of a randomized double blind placebo controlled clinical trial
Mayo Clinic Proceedings, 2000Co-Authors: Elliot A Schulman, Roger K Cady, Alice S Batenhorst, Dan Henry, Gayla D Putnam, Carolyn B Watson, Stephen OquinnAbstract:Objective To determine the effect of Sumatriptan on migraine-related workplace productivity loss. Patients and Methods In this randomized, doubleblind, placebo-controlled, parallel-group trial, adult migraineurs self-injected 6 mg of Sumatriptan or matching placebo to treat a moderate or severe migraine within the first 4 hours of a minimum of an 8-hour work shift. Outcome measures included productivity loss and number of patients returning to normal work performance 2 hours after injection and across the work shift, time to return to normal work performance, and time to headache relief. Results A total of 206 patients underwent screening, 140 (safety population) of whom returned for clinic treatment. Of these 140 patients, 119 received migraine treatment in the workplace (intent-to-treat population), 116 of whom comprised the study population. Of these 116 patients, 76 self-administered Sumatriptan, and 40 selfadministered placebo. Sumatriptan treatment tended to reduce median productivity loss 2 hours after injection compared with placebo (25.2 vs 29.9 minutes, respectively; P =.14). Significant reductions in productivity loss were obtained across the work shift after Sumatriptan treatment compared with placebo (36.8 vs 72.6 minutes, respectively; P =.001). Significantly more Sumatriptan-treated patients vs placebo-treated patients experienced shorter return to normal work performance at 2 hours (53/76 [70%] vs 12/40 [30%], respectively) and across the work shift (64/76 [84%] vs 23/40 [58%], respectively; P P =.004). Conclusion Across an 8-hourwork shift, Sumatriptan was superior to placebo in reducing productivity loss due to migraine.
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responsiveness of non ihs migraine and tension type headache to Sumatriptan
Cephalalgia, 1997Co-Authors: Roger K Cady, Donna L Gutterman, Jane Saiers, M E BeachAbstract:In a long-term efficacy and satiety study, 424 patients were treated with Sumatriptan (6 mg sc) for 1,904 migraine attacks. The patients were diagnosed with migraine based on IHS criteria but individual migraine attacks treated in the study were physician diagnosed; not necessarily required to meet IHS criteria. A re-analysis of the treatment response to open label Sumatriptan (6 mg sc) indicated that 43 patients had treated at least one migraine that fulfilled IHS criteria for tension-type headache. Analysis of this population revealed they treated 232 headaches. Of these headaches, 114 were classified per IHS criteria as migraine; 76 as tension-type; and 42 as. non-IHS migraine (not classifiable as IHS migraine or IHS tension-type headache). Of the 114 migraines a positive response to Sumatriptan occurred in 109 (96%) cases; of the 76 tension-types, 73 responded to Sumatriptan (97%); of the 42 non-IHS migraine, 40 (95%) responded to Sumatriptan. An equivalent response to Sumatriptan among three diagnost...
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Efficacy of subcutaneous Sumatriptan in repeated episodes of migraine
Neurology, 1993Co-Authors: Roger K Cady, Joseph D Sargent, J. Dexter, H. Markley, J. T. Osterhaus, C. J. WebsterAbstract:This double-blind, placebo-controlled, multicenter, crossover study investigated the efficacy and tolerability of Sumatriptan administered for up to three separate migraine attacks. One hundred twenty adults received Sumatriptan (SC, 6 mg; three attacks) and placebo (one attack). Patients completed questionnaires assessing the impact of migraine on their lives and the performance of Sumatriptan relative to their usual acute therapies. Sumatriptan statistically outperformed placebo on all efficacy measures, including pain severity; presence/absence of nausea, vomiting, phonophobia, and photophobia; rescue medication use; and clinical disability. Efficacy was consistently maintained with repeated administration. For all attacks, pain relief 90 minutes postdose occurred in 86% to 90% of Sumatriptan-treated patients, compared with 9% to 38% of placebo-treated patients. Sumatriptan was well tolerated, and the frequency and severity of adverse events did not change with repeated administration. Patients9 perceptions of Sumatriptan were consistent with clinical data demonstrating the drug9s high degree of efficacy and tolerability.
Donna L Gutterman - One of the best experts on this subject based on the ideXlab platform.
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tolerability of Sumatriptan clinical trials and post marketing experience
Cephalalgia, 2000Co-Authors: K M A Welch, Jane Saiers, N T Mathew, P Stone, Wayne D Rosamond, Donna L GuttermanAbstract:Through December 1998, Sumatriptan had been used to treat more than 236 million migraine attacks world-wide. In clinical trials alone, more than 88 000 migraine patients had treated more than 300 000 migraine attacks with Sumatriptan, and 2000 normal healthy volunteers had been exposed to the drug. This paper describes the safety and tolerability profile of Sumatriptan in three sections: adverse events reported in clinical trials, special issues, and spontaneous post-marketing reports of adverse reactions. Data from the extensive clinical trials programme coupled with information from nearly 10 years of experience in clinical practice demonstrate that Sumatriptan is generally well-tolerated, with an acceptable benefit–risk ratio when used properly. Significant cardiovascular and cerebrovascular events are rare but have been observed. This fact highlights the need for careful patient selection and vigilant adherence to the prescribing recommendations for Sumatriptan. The wealth of clinical trials and post-...
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responsiveness of non ihs migraine and tension type headache to Sumatriptan
Cephalalgia, 1997Co-Authors: Roger K Cady, Donna L Gutterman, Jane Saiers, M E BeachAbstract:In a long-term efficacy and satiety study, 424 patients were treated with Sumatriptan (6 mg sc) for 1,904 migraine attacks. The patients were diagnosed with migraine based on IHS criteria but individual migraine attacks treated in the study were physician diagnosed; not necessarily required to meet IHS criteria. A re-analysis of the treatment response to open label Sumatriptan (6 mg sc) indicated that 43 patients had treated at least one migraine that fulfilled IHS criteria for tension-type headache. Analysis of this population revealed they treated 232 headaches. Of these headaches, 114 were classified per IHS criteria as migraine; 76 as tension-type; and 42 as. non-IHS migraine (not classifiable as IHS migraine or IHS tension-type headache). Of the 114 migraines a positive response to Sumatriptan occurred in 109 (96%) cases; of the 76 tension-types, 73 responded to Sumatriptan (97%); of the 42 non-IHS migraine, 40 (95%) responded to Sumatriptan. An equivalent response to Sumatriptan among three diagnost...
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impact of Sumatriptan on workplace productivity nonwork activities and health related quality of life among hospital employees with migraine
Headache, 1996Co-Authors: George R Mushet, David P Miller, Bill Clements, Gayla Pait, Donna L GuttermanAbstract:This prospective, open-label study evaluated the effects of subcutaneous Sumatriptan versus usual therapy on workplace productivity, activity time outside of work, and health-related quality of life in 43 men or women who were hospital employees diagnosed with migraine according to International Headache Society criteria. Patients treated migraines with their usual therapy for 12 to 18 weeks followed by subcutaneous Sumatriptan for 6 months. Health-related quality of life measurements obtained at baseline, after usual therapy, and after Sumatriptan therapy included the Short Form-36 Health Surveyo and the Migraine-Specific Quality of Life Questionnaireo . Patient daily diaries were used to capture data on migraine symptoms and on Lost Workplace Productivity and Non-workplace Activity Time. Traditional clinical efficacy measures were obtained to support the pharmacoeconomic data. Clinical data showed that the percentage of treated migraine days per patient on which the patient experienced relief (moderate or severe pain reduced to mild or none) was 75% with Sumatriptan and 25% with usual therapy. The mean time to meaningful relief was 1.1 hours during the Sumatriptan phase and 4.2 hours during the usual therapy phase. Lost Workplace Productivity and Nonworkplace Activity Time was 35% lower with Sumatriptan therapy (1.5 hours) compared with usual therapy (2.3 hours). Time missed from work due to symptoms time worked with symptoms, and time normal activities were carried on with symptoms were each lower during Sumatriptan therapy compared with usual therapy. Scores on each of the three Migraine-Specific Quality of Life Questionnaire dimensions and on the Role-Emotional dimension of the Short Form-36 were significantly more favorable after Sumatriptan than after usual therapy (P<0.05). These data demonstrate that treatment of migraines with Sumatriptan for 6 months following usual therapy for 12 to 18 weeks was associated with improvement in clinical efficacy, reduction in lost workplace productivity and nonworkplace activity time, and enhancement of key dimensions of health-related quality of life among employees of a large university hospital.
M E Beach - One of the best experts on this subject based on the ideXlab platform.
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responsiveness of non ihs migraine and tension type headache to Sumatriptan
Cephalalgia, 1997Co-Authors: Roger K Cady, Donna L Gutterman, Jane Saiers, M E BeachAbstract:In a long-term efficacy and satiety study, 424 patients were treated with Sumatriptan (6 mg sc) for 1,904 migraine attacks. The patients were diagnosed with migraine based on IHS criteria but individual migraine attacks treated in the study were physician diagnosed; not necessarily required to meet IHS criteria. A re-analysis of the treatment response to open label Sumatriptan (6 mg sc) indicated that 43 patients had treated at least one migraine that fulfilled IHS criteria for tension-type headache. Analysis of this population revealed they treated 232 headaches. Of these headaches, 114 were classified per IHS criteria as migraine; 76 as tension-type; and 42 as. non-IHS migraine (not classifiable as IHS migraine or IHS tension-type headache). Of the 114 migraines a positive response to Sumatriptan occurred in 109 (96%) cases; of the 76 tension-types, 73 responded to Sumatriptan (97%); of the 42 non-IHS migraine, 40 (95%) responded to Sumatriptan. An equivalent response to Sumatriptan among three diagnost...
James W Alexander - One of the best experts on this subject based on the ideXlab platform.
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Sumatriptan naproxen for acute treatment of migraine a randomized trial
JAMA, 2007Co-Authors: Jan Lewis Brandes, Stuart R Stark, Susan E Spruill, James W Alexander, David Kudrow, Phillip C Ocarroll, James U Adelman, Francis J Odonnell, Pamela S Barrett, Shelly E LenerAbstract:ContextMultiple pathogenic mechanisms may be involved in generating the migraine symptom complex, and multimechanism-targeted therapy may confer advantages over monotherapy.ObjectiveTo evaluate the efficacy and safety of a fixed-dose tablet containing Sumatriptan succinate and naproxen sodium relative to efficacy and safety of each monotherapy and placebo for the acute treatment of migraine.Design, Setting, and ParticipantsTwo replicate, randomized, double-blind, single-attack, parallel-group studies conducted among 1461 (study 1) and 1495 (study 2) patients at 118 US clinical centers who were diagnosed as having migraine and received study treatment for a moderate or severe migraine attack.InterventionsPatients were randomized in a 1:1:1:1 ratio to receive a single tablet containing Sumatriptan, 85 mg, and naproxen sodium, 500 mg; Sumatriptan, 85 mg (monotherapy); naproxen sodium, 500 mg (monotherapy); or placebo, to be used after onset of a migraine with moderate to severe pain.Main Outcome MeasuresPrimary outcome measures included the percentages of patients with headache relief 2 hours after dosing, absence of photophobia, absence of phonophobia, and absence of nausea for the comparison between Sumatriptan–naproxen sodium and placebo, and the percentages of patients with sustained pain-free response for the comparison between Sumatriptan–naproxen sodium and each monotherapy.ResultsSumatriptan–naproxen sodium was more effective than placebo for headache relief at 2 hours after dosing (study 1, 65% vs 28%; P<.001 and study 2, 57% vs 29%; P<.001), absence of photophobia at 2 hours (58% vs 26%; P<.001 and 50% vs 32%; P<.001), and absence of phonophobia at 2 hours (61% vs 38%; P<.001 and 56% vs 34%; P<.001). The absence of nausea 2 hours after dosing was higher with Sumatriptan–naproxen sodium than placebo in study 1 (71% vs 65%; P = .007), but in study 2 rates of absence of nausea did not differ between Sumatriptan–naproxen sodium and placebo (65% vs 64%; P = .71). For 2- to 24-hour sustained pain-free response, Sumatriptan–naproxen sodium was superior at P<.01 (25% and 23% in studies 1 and 2, respectively) to Sumatriptan monotherapy (16% and 14% in studies 1 and 2), naproxen sodium monotherapy (10% and 10% in studies 1 and 2), and placebo (8% and 7% in studies 1 and 2). The incidence of adverse events was similar between Sumatriptan–naproxen sodium and Sumatriptan monotherapy.ConclusionSumatriptan, 85 mg, plus naproxen sodium, 500 mg, as a single tablet for acute treatment of migraine resulted in more favorable clinical benefits compared with either monotherapy, with an acceptable and well-tolerated adverse effect profile.Trial Registrationclinicaltrials.gov Identifiers: NCT00434083 (study 1); NCT00433732 (study 2)
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Sumatriptan and naproxen sodium for the acute treatment of migraine
Headache, 2005Co-Authors: Timothy R Smith, Abraham Sunshine, Stuart R Stark, Diane E Littlefield, Susan E Spruill, James W AlexanderAbstract:Objective.—To evaluate the efficacy and tolerability of treatment with a combination of Sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg administered concurrently in the acute treatment of migraine. Background.—The pathogenesis of migraine involves multiple peripheral and central neural mechanisms that individually have been successful targets for acute (abortive) and preventive treatment. This suggests that multimechanism therapy, which acts on multiple target sites, may confer improved efficacy and symptom relief for patients with migraine. Design and Methods.—This was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, four-arm study. Participants (n = 972) treated a single moderate or severe migraine attack with placebo, naproxen sodium 500 mg, Sumatriptan 50 mg, or a combination of Sumatriptan 50 mg and naproxen sodium 500 mg. In the latter two treatment arms, the Sumatriptan tablets were encapsulated in order to achieve blinding of the study. Results.—In the Sumatriptan plus naproxen sodium group, 46% of subjects achieved 24-hour pain relief response (primary endpoint), which was significantly more effective than Sumatriptan alone (29%), naproxen sodium alone (25%), or placebo (17%) (P < .001). Two-hour headache response also significantly favored the Sumatriptan 50 mg plus naproxen sodium 500 mg therapy (65%) versus Sumatriptan (49%), naproxen sodium (46%), or placebo (27%) (P < .001). A similar pattern of between-group differences was observed for 2-hour pain-free response and sustained pain-free response (P < .001). The incidence of headache recurrence up to 24 hours after treatment was lowest in the Sumatriptan plus naproxen sodium group (29%) versus Sumatriptan alone (41%; P = .048), versus naproxen sodium alone (47%; P = .0035), and versus placebo (38%; P = .08). The incidences of the associated symptoms of migraine were significantly lower at 2 hours following Sumatriptan 50 mg plus naproxen sodium 500 mg treatment versus placebo (P < .001). The frequencies and types of adverse events reported did not differ between treatment groups, with dizziness and somnolence being the most common. Conclusions.—This is among the first prospective studies to demonstrate that multimechanism acute therapy for migraine, combining a triptan and an analgesic, is well tolerated and offers improved clinical benefits over monotherapy with these selected standard antimigraine treatments. Specifically, Sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg resulted in significantly superior pain relief as compared to monotherapy with either Sumatriptan 50 mg (encapsulated) or naproxen sodium 500 mg for the acute treatment of migraine. Because encapsulation of the Sumatriptan for blinding purposes may have altered its pharmacokinetic profile and thereby decreased the efficacy responses, additional studies are warranted that do not involve encapsulation of the active treatments and assess the true onset of action of multimechanism therapy in migraine. This study did show that the combination of Sumatriptan and naproxen sodium was well tolerated and that there was no significant increase in the incidence of adverse events compared to monotherapy. Ke yw ords: migraine, Sumatriptan, acute treatment, NSAIDs, naproxen sodium, clinical trial Abbreviations: NSAIDs nonsteroidal anti-inflammatory drugs, CGRP calcitonin gene-related peptide, IHS
