Stewart J. Tepper

Efficacy of Gabapentin in Migraine Prophylaxis

Objective.—To compare gabapentin with placebo for use as a prophylactic agent in patients with migraine (with or without aura).

Transformed Migraine and Medication Overuse in a Tertiary Headache Centre — Clinical Characteristics and Treatment Outcomes

Studies suggest that a substantial proportion of headache sufferers presenting to headache clinics may overuse acute medications. In some cases, overuse may be responsible for the development or maintenance of a chronic daily headache (CDH) syndrome. The objectives of this study are to evaluate patterns of analgesic overuse in patients consulting a headache centre and to compare the outcomes in a group of patients who discontinued medication overuse to those of a group who continued the overuse, in patients with similar age, sex and psychological profile. We reviewed charts of 456 patients with transformed migraine (TM) and acute medication overuse defined by one of the following criteria: 1. Simple analgesic use (> 1000 mg ASA/acetaminophen) > 5 days/week; 2. Combination analgesics use (caffeine and/or butalbital) > 3 tablets a day for > 3 days a week; 3. Opiate use > 1 tablet a day for > 2 days a week; 4. Ergotamine tartrate use: 1 mg PO or 0.5 mg PR for > 2 days a week. For triptans, we empirically considered overuse > 1 tablet per day for > 5 days per week. Patients who were able to undergo detoxification and did not overuse medication (based on the above definition) after one year of follow-up were considered to have successful detoxification (Group 1). Patients who were not able to discontinue offending agents, or returned to a pattern of medication overuse within one year were considered to have unsuccessful detoxification (Group 2). We compared the following outcomes after one year of follow-up: Number of days with headache per month; Intensity of headache; Duration of headache; Headache score (frequency x intensity). The majority of patients overused more than one type of medication. Numbers of tablets taken ranged from 1 to 30 each day (mean of 5.2). Forty-eight (10.5%) subjects took > 10 tablets per day. Considering patients seen in the last 5 years, we found the following overused substances: Butalbital containing combination products, 48%; Acetaminophen, 46.2%; Opioids, 33.3%; ASA, 32.0%; Ergotamine tartrate, 11.8%; Sumatriptan, 10.7%; Nonsteroidal anti-inflammatory medications other than ASA, 9.8%; Zolmitriptan, 4.6%; Rizatriptan, 1.9%; Naratriptan, 0.6%. Total of all triptans, 17.8%. Of 456 patients, 318 (69.7%) were successfully detoxified (Group 1), and 138 (30.3%) were not (Group 2). The comparison between groups 1 and 2 after one year of follow-up showed a decrease in the frequency of headache of 73.7% in group 1 and only 17.2% in group 2 (P < 0.0001). Similarly, the duration of head pain was reduced by 61.2% in group 1 and 14.8% in group 2 (P < 0.0001). The headache score after one year was 18.8 in group 1 and 54 in group 2 (P < 0.0001). A total of 225 (70.7%) successfully detoxified subjects in Group 1 returned to an episodic pattern of migraine, compared to 21 (15.3%) in Group 2 (P < 0.001). More rigorous prescribing guidelines for patients with frequent headaches are urgently needed. Successful detoxification is necessary to ensure improvement in the headache status when treating patients who overuse acute medications.

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.

Prevalence and Diagnosis of Migraine in Patients Consulting Their Physician With a Complaint of Headache: Data From the Landmark Study

Context.—Headache experts have suggested that to improve the recognition of migraine, patients with a stable pattern of episodic, disabling headache and a normal physical exam should be considered to have migraine in the absence of contradictory evidence. The premise upon which this approach is based—that is, that episodic, recurrent primary headache in the clinic is usually migraine—has not been evaluated in prospective clinical studies.

LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine.

Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY293558, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist, is effective in preclinical models of migraine. We therefore tested LY293558 in acute migraine. We conducted a randomized, triple-blind, parallel-group, double-dummy, multicentre trial of 1.2 mg/kg intravenous (IV) LY293558, 6 mg subcutaneous (SC) sumatriptan, or placebo in the treatment of acute migraine. The primary efficacy variable was the headache response rate, i.e. headache score improvement from moderate/severe at baseline to mild/none at 2 h. Of 45 enrolled patients, 44 patients (20M:24F; mean age ± SD = 40 ± 9 years) completed the study. Response rates were 69% for LY293558 (P = 0.017 vs. placebo), 86% for sumatriptan (P < 0.01 vs. placebo) and 25% for placebo. LY293558 and sumatriptan were superior to placebo (P < 0.01 for all comparisons) on all other measures of improvement in pain and migraine associated symptoms. Fifteen percent of patients who took LY293558 reported adverse events (AEs) (n = 2; one mild, one severe). Fifty-three percent of patients who took sumatriptan (n = 8; seven mild, one moderate) and 31% of those who received placebo reported AEs (n = 5; four mild, one severe). The efficacy and safety results of LY293558 in this small migraine proof of concept trial, together with supportive preclinical data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine. Larger trials are needed to further test the hypothesis.

Chronic daily headache: identification of factors associated with induction and transformation.

Background.—Chronic daily headache (CDH) is one of the more frequently encountered headache syndromes at major tertiary care centers. The analysis of factors related to the transformation from episodic to chronic migraine (CM) and to the de novo development of new daily persistent headache (NDPH) remain poorly understood.

Electrical stimulation of sphenopalatine ganglion for acute treatment of cluster headaches.

(Headache 2010;50:1164‐1174)

Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study

Magnesium sulphate has been used in the acute treatment of migraines; some studies found it to be a highly effective medication in the acute control of migraine pain and associated symptoms. This randomized, double-blind, placebo-controlled study assesses the effect of magnesium sulphate on the pain and associated symptoms in patients with migraine without aura and migraine with aura. Sixty patients in each group were assigned at random to receive magnesium sulphate, 1000 mg intravenously, or 0.9% physiological saline, 10 ml. We used seven parameters of analgesic evaluation and an analogue scale to assess nausea, photophobia and phonophobia. In the migraine without aura group there was no statistically significant difference in the patients who received magnesium sulphate vs. placebo in pain relief. The analgesic therapeutic gain was 17% and number needed to treat was 5.98 at 1 h. There was also no statistical difference in relief of nausea. We did observe a significant lower intensity of photophobia and phonophobia in patients who received magnesium sulphate. In the migraine with aura group patients receiving magnesium sulphate presented a statistically significant improvement of pain and of all associated symptoms compared with controls. The analgesic therapeutic gain was 36.7% at 1 h. A smaller number of patients continued to have aura in the magnesium sulphate group compared with placebo 1 h after the administration of medication. Our data support the idea that magnesium sulphate can be used for the treatment of all symptoms in migraine with aura, or as an adjuvant therapy for associated symptoms in patients with migraine without aura.

Chronic daily headache in a tertiary care population: correlation between the International Headache Society diagnostic criteria and proposed revisions of criteria for chronic daily headache.

The International Headache Society (IHS) has been criticized for its approach to classification of chronic daily headache (CDH); Silberstein and Lipton criteria provide an alternative to this approach. The aim of this study is to apply the alternative diagnostic approaches to a sample of CDH patients consulting in specialty care. Our sample consisted of 638 patients with CDH. Patients were classified according to both classification systems. Patients were predominantly female (65.0%), with ages ranging from 11 to 88 years. According to the Silberstein and Lipton classification, we found eight different diagnoses. The most common diagnosis was chronic migraine (87.4%), followed by new daily persistent headache (10.8%). Just six patients had chronic tension- type headache (CTTH). Applying the IHS criteria we found 14 different diagnoses. Migraine was found in 576 (90.2%) patients. CTTH occurred in 621 (97.3%), with only 10 (1.57%) having this as the sole diagnosis. We conclude that both systems allow for the classification of most patients with CDH when daily headache diaries are available. The main difference is that the IHS classification is cumbersome and requires multiple diagnoses. The Silberstein and Lipton system is easier to apply, and more parsimonious. These findings support revision of the IHS classification system to include chronic migraine.

Primary chronic daily headache and its subtypes in adolescents and adults

Objectives: To determine the relative frequency of chronic daily headache (CDH) subtypes in adolescents and to compare the distribution of CDH subtypes in adolescents and adults of various ages. Methods: Adolescents (13 to 17 years, n = 170) and adults (18 or older, n = 638) were recruited during the same time frame. CDH subtypes were classified according the criteria proposed by Silberstein and Lipton (1996) as transformed migraine (TM), chronic tension-type headache (CTTH), new daily persistent headache (NDPH), and hemicrania continua (HC). Results: Among adolescents and adults there were substantial differences in the distribution of CDH subtypes. The relative frequency of TM was lower in adolescents (68.8% vs 87.4%, p < 0.001), while NDPH (21.1% vs 10.8%, p < 0.001) and CTTH (10.1% vs 0.9%, p < 0.0001) were more common. HC (0 vs 0.9%, NS) was equally rare. The lower relative frequency of TM in adolescents was accounted for by TM with medication overuse (TM+), much more common in adults (28.2% vs 62.5%, p < 0.001). In fact, TM without medication overuse (TM−) was more common in adolescents (40.5% vs 24.9%, p < 0.001). The relative frequency of TM+ increased until the age of 50 years (p < 0.001). Conclusions: In adolescents with CDH, TM usually develops without medication overuse. Adolescents with the early onset form of TM may develop the disorder in the absence of medication overuse because they are at increased biologic risk.