Letter to the Editor Sublingual Feverfew/Ginger (LipiGesic M) Reanalysis of Data Roger Cady MD, Roger Cady MD Headache Care Center – Medicine, Springfield, MO, USASearch for more papers by this authorDaniel Serrano PhD, Daniel Serrano PhD Vedanta – Research, Chapel Hill, NC, USASearch for more papers by this authorRichard Lipton MD, Richard Lipton MD Albert Einstein College of Medicine – Neurology, Bronx, NY, USASearch for more papers by this authorRebecca Browning BS, Rebecca Browning BS Clinvest Inc – Statistics, Springfield, MO, USASearch for more papers by this author Roger Cady MD, Roger Cady MD Headache Care Center – Medicine, Springfield, MO, USASearch for more papers by this authorDaniel Serrano PhD, Daniel Serrano PhD Vedanta – Research, Chapel Hill, NC, USASearch for more papers by this authorRichard Lipton MD, Richard Lipton MD Albert Einstein College of Medicine – Neurology, Bronx, NY, USASearch for more papers by this authorRebecca Browning BS, Rebecca Browning BS Clinvest Inc – Statistics, Springfield, MO, USASearch for more papers by this author First published: 22 February 2013 https://doi.org/10.1111/j.1526-4610.2012.02282.xCitations: 1 Conflict of Interest: Roger Cady has served as a consultant for GlaxoSmithKline, Merck, and Ortho-McNeil, and received research grants from Allergan, Endo Pharmaceuticals, GlaxoSmithKline, Merck, PuraMed Bioscience, and Wyeth. Authors Daniel Serrano, Richard Lipton, and Rebecca Browning have nothing to disclose in relation to this letter to the editor. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Cady RK, Goldstein J, Nett R, Mitchell R, Beach ME, Browning R. A double-blind, placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic M) in the treatment of migraine. Headache. 2011; 7: 1078-1086. 2 Satterthwaite FE. Approximate distribution of estimates of variance components. Biometrics. 1946; 2: 110-114. 3 Kenward MG, Roger JH. Small sample inference for fixed effects from restricted maximum likelihood. Biometrics. 1997; 53: 983-997. 4 McCullagh P, Nelder JA. Generalized Linear Models, 2nd edn. Boca Raton, FL: Chapman & Hall/CRC; 1989. 5 Demidenko E. Mixed Models: Theory and Applications. New York, NY: John Wiley & Sons; 2004. 6 Agresti A. Categorical Data Analysis, 2nd edn. New York, NY: John Wiley & Sons; 2002. Citing Literature Volume53, Issue2February 2013Pages 384-386 ReferencesRelatedInformation

( Headache 2012;52:749‐764) Objective.— To compare the efficacy and clinical benefit of 2 paradigms of migraine prevention using pre‐emptive frovatriptan and daily topiramate. The study compares the paradigms of pre‐emptive use of frovatriptan, a drug approved for acute migraine, and the daily use of topiramate, a Federal Drug Administration‐approved and ‐accepted standard for migraine prophylaxis. Background.— Traditionally, preventive treatment of migraine required daily medication. However, recent studies suggest that pre‐emptive prophylaxis may be beneficial to those migraineurs who can predict an attack of migraine based on premonitory symptoms and treat during that phase. Methods.— A total of 76 adult subjects with a diagnosis of migraine were screened for the study. During a 1‐month baseline period, subjects demonstrated through a daily diary that they predicted at least 50% of migraine attacks during the premonitory phase and treated with their usual medication. Of these, 55 were randomized to either Group A (daily topiramate) or Group B (frovatriptan during premonitory symptoms); 44 completed the study. The treatment period lasted 2 months. The subjects answered the Migraine‐Specific Quality of Life Questionnaire at randomization, and at Weeks 4 and 8. The revised Patient Perception of Migraine Questionnaire was answered 24 hours after taking frovatriptan (Group A, for break‐through headaches; Group B, treatment during premonitory symptoms). Results.— The number of migraine attacks and headache days per month decreased significantly from baseline for both Groups A and B. Subjects in Group A had considerably more adverse events leading to study withdrawal than in Group B (18% vs 4%). Though this study was not powered to directly compare the efficacy of the 2 drugs, topiramate showed superiority over frovatriptan at Month 2 in reduction of headache days, which was a secondary end point in the study ( P = .036). Conclusions.— This pilot study demonstrated that statistical benefit for reduction of headache days over baseline for both pre‐emptive frovatriptan and daily topiramate. Subjects utilizing pre‐emptive frovatriptan experienced fewer adverse events leading to study withdrawal. Subjects utilizing daily topiramate had fewer headache days at Month 2.

ObjectiveTo assess the cognitive effects of acute migraine and the subsequent impact of acute treatment in a controlled setting.BackgroundCognitive dysfunction may be an associated symptom in patients with migraine with or without aura. The loss of cognitive efficiency in migraine may be disabling and is often under recognized.MethodsThirty migraine patients were prospectively studied for cognitive function before and then at the beginning of a migraine using a computerized cognitive battery (Mental Efficacy Workload Test). Each patient then was treated for 2 headaches in a cross‐over manner with sumatriptan‐naproxen (Treximet®) or placebo in a double‐blind, placebo‐controlled fashion with cognitive testing repeated at 1 and 2 hours post‐dose.ResultsTwenty‐five of the 30 screened migraine subjects completed study‐specific procedures and were included in the data analyses. There were no significant side effects from Treximet or placebo and no serious adverse events. At the onset of headache, there was a statistically significant decline in overall cognitive efficiency compared with the baseline cognitive testing (migraine‐free) for all subjects (P = .001 paired samples t‐test). For subjects taking Treximet compared with taking placebo, there was a statistically significant return to cognitive efficiency by measures of immediate and sustained attention, visual‐spatial awareness, mental flexibility, and reaction time between 1 hour and 2 hours (P = .05). There was no statistical significance between patients taking Treximet or placebo in measures of complex reasoning or fine motor coordination. Subanalysis showed a correlation between headache severity and Performance Index in the Treximet group but not in the placebo group (∼Fig. ).ConclusionsThere is a significant decline in global cognitive efficiency at the onset of an attack of migraine. The use of Treximet allows a significantly faster recovery time in some measures of cognitive efficiency compared with placebo. Decline of cognitive efficiency may be independent of headache severity.

Background.-Therapeutic needs of migraineurs vary considerably from patient to patient and even attack to attack. Some attacks require high-end therapy, while other attacks have treatment needs that are less immediate. While triptans are considered the "gold standard" of migraine therapy, they do have limitations and many patients are seeking other therapeutic alternatives. In 2005, an open-label study of feverfew/ginger suggested efficacy for attacks of migraine treated early during the mild headache phase of the attack.Methods/Materials.-In this multi-center pilot study, 60 patients treated 221 attacks of migraine with sublingual feverfew/ginger or placebo. All subjects met International Headache Society criteria for migraine with or without aura, experiencing 2-6 attacks of migraine per month within the previous 3 months. Subjects had <15 headache days per month and were not experiencing medication overuse headache. Inclusion required that subjects were able to identify a period of mild headache in at least 75% of attacks. Subjects were required to be able to distinguish migraine from non-migraine headache. Subjects were randomized 3: 1 to receive either sublingual feverfew/ginger or a matching placebo and were instructed but not required to treat with study medication at the earliest recognition of migraine.Results.-Sixty subjects treated 208 evaluable attacks of migraine over a 1-month period; 45 subjects treated 163 attacks with sublingual feverfew/ginger and 15 subjects treated 58 attacks with a sublingual placebo preparation. Evaluable diaries were completed for 151 attacks of migraine in the population using feverfew/ginger and 57 attacks for those attacks treated with placebo. At 2 hours, 32% of subjects receiving active medication and 16% of subjects receiving placebo were pain-free (P = .02). At 2 hours, 63% of subjects receiving feverfew/ginger found pain relief (pain-free or mild headache) vs 39% for placebo (P = .002). Pain level differences on a 4-point pain scale for those receiving feverfew/ginger vs placebo were -0.24 vs -0.04 respectively (P = .006). Feverfew/ginger was generally well tolerated with oral numbness and nausea being the most frequently occurring adverse event.Conclusion.-Sublingual feverfew/ginger appears safe and effective as a first-line abortive treatment for a population of migraineurs who frequently experience mild headache prior to the onset of moderate to severe headache.