Reviewed: 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;51(7):1078-1086.
Migraine is a complex neurobiological disease characterized not only by headache, but also by nausea, photophobia (intolerance of bright light), phonophobia (intolerance of noise and speech), autonomic nasal symptoms, muscle pain, and cognitive disruption. Some attacks require bed rest, while others produce only mild or limited disability. Common acute treatments include acetaminophen/aspirin/caffeine combinations and over-the-counter nonsteroidal anti-inflammatory medications, as well as prescription products such as triptans and nonsteroidal anti-inflammatories. Because oral medications do not work for all migraine sufferers and because prescription medications are associated with adverse events, high costs, and quantity limits, there is a need for affordable, effective, alternative treatments.
The double-blind, placebo-controlled pilot study reviewed herein compared the efficacy of a unique lipid-based formulation of the sublingual homeopathic product LipiGesic™ M (PuraMed BioScience; Schofield, Wisconsin), which contains what the manufacturer states is a “3x”* preparation of feverfew (Tanacetum parthenium, Asteraceae) herb and a “2x”* preparation of ginger (Zingiber officinale, Zingiberaceae) root, (in a base of “Colloidal Silicon Dioxide, Natural Peppermint Flavor, N.F. Grade Olive Oil.” A peppermint (Mentha x piperita, Lamiaceae)-flavored sublingual preparation was used as a placebo. The trial tested the herbal-homeopathic preparation as an abortive treatment for acute episodic migraine. Secondary objectives included evaluation of persistent or recurrent headache 2 to 24 hours following treatment, assessment of adverse events, and comparison of migraine questionnaire scores between the treatment and placebo.
Sixty subjects enrolled in the study; data for 59 were included in the analysis. The subjects (46 women and 14 men) were aged 13 to 60 years, met criteria for International Headache Society migraine with or without aura, and had a history of migraine for more than 1 year. They had experienced between 2 to 6 attacks per month during the previous 3 months; at least 75% of their attacks had begun with mild headache. The subjects were able to differentiate migraine from non-migraine headache.
Conducted at 3 investigational sites, the study included 2 visits: one at screening and 1 exit visit 1 month later. The subjects were randomized 3:1 to receive either sublingual feverfew/ginger (n=45) or a matching placebo (n=15). The subjects were asked to treat all migraine attacks over the 1-month period, regardless of the intensity. They were instructed to treat with sequential administrations of 2 unit dose applicators. The liquid from 1 applicator was applied sublingually, held under the tongue for 60 seconds, and then swallowed. After 5 minutes, the second dose was administered. If headache pain persisted 1 hour later, the subjects could take a further 2 unit dose.
At screening, all subjects provided a medical, medication, and migraine history. Vital signs were recorded, and the subjects completed the Revised Patient Perception of Migraine Questionnaire (PPMQ-R). At the second visit, the subjects returned their completed headache diaries documenting the onset of headache pain and presence of migraine-associated symptoms, time of treatment with study medication, symptoms at 1 and 2 hours following treatment, time of relief, recurrence of symptoms within 24 hours after treatment, and adverse events.
Of those subjects using sublingual feverfew/ginger, 32% reported being pain-free at 2 hours post-dose compared with 16% using placebo (P=0.02). At 2 hours post-dose, the percentage of attacks rated as no pain or mild pain was 64% for sublingual feverfew/ginger compared with 39% for placebo (P=0.003). Pain level differences on a 4-point scale were -0.24 for those receiving feverfew/ginger and -0.04 for those using placebo (P=0.006). At 2 hours post-treatment, a statistically significant difference was noted in migraine symptoms and headache characteristics between the 2 groups. This included superiority of the treatment over placebo in eliminating the pulsating character of the headache (P=0.007); the worsening of headache with activity (P=0.015); and the presence of light sensitivity (P=0.001), sound-sensitivity (P=0.003), and nausea (P=0.02). The treatment was well tolerated.
Recurrence of headache was not analyzable because there were only 9 attacks in the placebo group that were pain-free at 2 hours after treatment. Of the 47 attacks that became pain-free at 2 hours in the active group, the recurrent rate was 20.4%, meaning return of moderate to severe migraine pain or use of rescue medication (i.e., conventional treatment) within 22 hours of becoming pain-free. Evaluation of the subjects’ responses on the PPMQ-R revealed statistical superiority for the treatment over placebo in total score (P=0.30), efficacy (P=0.04), and functionality (P=0.02).
According to the authors, the complex layers involved in the treatment of acute migraine are not addressed in clinical guidelines. Often, adverse events are interpreted by patients differently than by their healthcare providers. Consequently, an “adherence gap” exists between what providers think patients need for treatment and what patients seek from treatment. This is apparent, say the authors, in the fact that the use of triptans, considered the “gold standard” of migraine treatment, is not increasing by those with migraine headaches. Patients are seeking more than what triptans can provide. “Understanding this ‘adherence gap’ represents the distance between evidence-based medicine and patient-centered care,” write the authors, calling for future studies to understand more completely the treatment dynamics of the migraine population.
The authors conclude that this study supports the efficacy of lipid-based sublingual feverfew/ginger in the acute treatment of migraine when administered early in the migraine attack.
* 3x and 2x refer to the degree of dilution in the process of producing a homeopathic preparation from a “mother tincture,” an ethanolic and/or water extract at a ratio of 1:1.
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