Fred D. Sheftell

Effect of early intervention with sumatriptan on migraine pain: Retrospective analyses of data from three clinical trials

OBJECTIVE This study assessed the efficacy of sumatriptan 50- and 100-mg tablets in the treatment of migraine attacks while the pain is mild rather than moderate/severe. BACKGROUND Results from The Spectrum Study suggested that early treatment of migraine attacks with sumatriptan 50-mg tablets while the pain is mild might enhance pain-free response and reduce headache recurrence. METHODS Retrospective analyses of headaches treated during mild pain were performed using data from 3 studies of sumatriptan tablets (protocols S2CM09, S2BT25, and S2BT26). Our primary interest was pain-free response 2 and 4 hours after dosing; secondary interests were use of a second dose of medication, clinical disability (as measured on a 4-point disability scale), migraine-associated symptoms, meaningful pain relief (patient defined), time to meaningful relief, sustained pain-free response, and proportion of attacks in which pain had worsened 2 and 4 hours after dosing, all of which were compared in headaches treated during mild versus moderate/severe pain. RESULTS In S2CM09, 92 patients treated 118 headaches during mild pain. Rates of pain-free response were higher 2 hours after dosing with sumatriptan 50 mg (51%) or 100 mg (67%; P < 0.05) compared with placebo (28%), and were higher with early treatment of mild pain compared with treatment of moderate/severe pain at 2 hours (sumatriptan 50 mg: mild pain, 51%; moderate/severe pain, 31%; P < 0.05; sumatriptan 100 mg: mild pain, 67%; moderate/severe pain, 36%) and 4 hours (50 mg: 75% vs 56%; 100 mg: 90% vs 61%; P < 0.05). Early intervention also resulted in less redosing than when moderate/severe pain was treated (50 mg: 21% vs 32%; 100 mg: 20% vs 29%). More attacks treated early with sumatriptan 50 or 100 mg were associated with normal function 4 hours after dosing compared with placebo (70% and 93% vs 46%, respectively). Sustained pain-free response rates 2 to 24 hours after early dosing with sumatriptan 50 or 100 mg were also higher (34% and 53%, respectively) compared with treatment of moderate/severe pain (19% and 24%, respectively). Early treatment with sumatriptan 100 mg produced significantly higher pain-free rates at 2 hours after dosing (P < 0.001) than did ergotamine plus caffeine (S2BT25: 69% vs 34%, respectively) or aspirin plus metoclopramide (S2BT26: 73% vs 25%, respectively). CONCLUSIONS Sumatriptan 50- and 100-mg tablets are effective whether pain is mild or moderate/severe. However, treatment with sumatriptan while pain is mild provides high pain-free response rates while reducing the need for redosing, benefits not seen with ergotamine plus caffeine or aspirin plus metoclopramide.

Assessment of migraine disability using the migraine disability Assessment (MIDAS) questionnaire: A comparison of chronic migraine with episodic migraine

Background.—Chronic migraine is the most common type of chronic daily headache seen in headache tertiary care centers. Most patients with chronic migraine report their ability to function and feeling of well‐being as severely impaired.

Primary Headaches: A Convergence Hypothesis

After reviewing the historic differentiation between migraine and tension‐type headache, the authors note that the similarities between these two types of primary headaches outweigh the differences, and so hypothesize that these headaches share a common pathophysiology. The convergence hypothesis for primary headaches links the clinical features of an evolving headache to current pathophysiological models. The authors suggest that successive symptoms experienced clinically reflect an escalating pathophysiological process, beginning with the premonitory period and progressing into tension‐type headache and, if uninterrupted, finally into migraine. The clinical manifestations of other headache types, such as so‐called sinus headache or temporomandibular headache, may also be explained by this model. A convergence hypothesis for primary headaches has important implications for earlier recognition, diagnosis, and treatment.

Migraine and psychiatric comorbidity: from theory and hypotheses to clinical application.

Objective.—To review psychiatric issues that accompany migraine and means of addressing these issues.

Medications Associated with Probable Medication Overuse Headache Reported in a Tertiary Care Headache Center Over a 15-Year Period

Objectives.—To evaluate the substances associated with medication overuse headache (MOH) in a headache center, over the course of the past 15 years.

A Double-Blind Placebo-Controlled Trial of Intranasal Capsaicin for Cluster Headache

It has been suggested that treatment of cluster headache (CH) patients with topical capsaicin may desensitize sensory neurons by depleting the nerve terminals of substance P. We attempted to determine whether capsaicin is effective in aborting CH attacks. Patients in acute cluster were randomized to receive either capsaicin or placebo in the ipsilateral nostril for 7 days. Patients recorded the severity of each headache for 15 days. Headaches on days 8–15 of the study were significantly less severe in the capsaicin group vs the placebo group. There was also a significant decrease in headache severity in the capsaicin group on days 8–15 compared to days 1–7, but not in the placebo group. Episodic CH patients appeared to benefit more than chronic CH patients. These results indicate that intranasal capsaicin may provide a new therapeutic option for the treatment of this disease.

Memantine in the Preventive Treatment of Refractory Migraine

Objectives.— To assess the efficacy and tolerability of memantine (MEM) in the preventive treatment of refractory migraine.

The pathophysiology of migraine.

BACKGROUND—Migraine results from episodic changes in central nervous system physiologic function in hyperexcitable brain manifested by abnormal energy metabolism, lowered threshold for phosphene generation, and increased contingent negative variation. Human functional magnetic resonance imaging and magnetoencepholography data strongly suggest that aura is caused by cortical spreading depression. REVIEW SUMMARY–Brain hyperexcitability may be caused by low magnesium levels, mitochondrial abnormalities with abnormal phosphorylation of adenosine 5’-diphosphate, a dysfunction related to nitric oxide, or calcium channelopathy. Low magnesium can result in opening of calcium channels, increased intracellular calcium, glutamate release, and increased extracellular potassium, which may in turn trigger cortical spreading depression. Mitochondrial dysfunction has been suggested by a low phosphocreatine:Pi ratio and a possible response by migraine patients to riboflavin prophylaxis. Nitroglycerine administration results in a delayed migraine-like headache in migraine patients but not in control patients, and a nonspecific nitric oxide synthase inhibitor aborted migraine at 2 hours in the majority of tested migraine patients compared to controls. Many patients with familial hemiplegic migraine have a missense mutation in the P/Q calcium channel, so that this form of migraine, at least, is associated with a demonstrable calcium channelopathy. CONCLUSIONS–The generation of migraine occurs centrally in the brain stem, sometimes preceded by cortical spreading depression and aura. Activation of the trigeminovascular system stimulates perivascular trigeminal sensory afferent nerves with release of vasoactive neuropeptides, resulting in vasodilation and transduction of central nociceptive information. There is then a relay of pain impulses to central second- and third-order neurons and activation of brain stem autonomic nuclei to induce associated symptoms.

Montelukast in the Prophylaxis of Migraine: A Potential Role for Leukotriene Modifiers

Objective.–Clinical observation of a decrease in migraine frequency in patients with comorbid asthma taking montelukast, a specific D4 leukotriene receptor antagonist, or zafirlukast, another leukotriene receptor antagonist, prompted us to explore a possible role for leukotriene modifiers in the treatment of migraine. (A further prompt was a pharmacist colleagues observation that a number of patients on these agents reported a decreased sensitivity to perfume triggers and improvement in migraine.)

Satisfaction With Current Migraine Therapy: Experience From 3 Centers in US and Sweden

Objective.—To assess the level of satisfaction and determinants of satisfaction or dissatisfaction of patients presenting in tertiary care, in regard to their usual care (UC) for the acute treatment of migraine.