Time course of adverse events most commonly associated with topiramate for migraine prevention.

The efficacy, safety and tolerability of topiramate has been demonstrated in three large multicenter, randomized, double-blind, placebo-controlled trials. To characterize the time course of adverse events (AEs) that led to treatment discontinuation in >/=2% of patients who received topiramate 100 mg/day during three pivotal, multicenter, randomized, double-blind, placebo-controlled, and 26-week trials. The pooled population comprised all randomized patients who reported safety data during the double-blind phase (topiramate 100 mg/day, n = 386; placebo n = 372), which consisted of a 4-week titration period and a 22-week maintenance period. Incidence, time to onset, and cumulative mean rate of AEs were assessed. Overall, AEs led to treatment discontinuation in 24.9% of patients receiving topiramate 100 mg/day and 11.0% receiving placebo (P < 0.001). AEs leading to discontinuation during the double-blind phase in > or =2% of patients included paresthesia (8.0% discontinued), any cognitive symptoms (7.3% discontinued), fatigue (4.7% discontinued), insomnia (3.4% discontinued), nausea (2.3% discontinued), loss of appetite, anxiety, and dizziness (2.1% discontinued because each AE). Most AEs began during the titration period. Paresthesia, any cognitive symptoms, nausea, and loss of appetite occurred at a higher rate in the topiramate group than in the placebo group (P < 0.01). AEs leading to discontinuation of topiramate are probably to occur during dose titration. If a patient has not experienced one of these AEs within the first 6 weeks of initiating topiramate 100 mg/day, these AEs are unlikely to occur.

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

Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY293558, an alpha-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.

The use of ibuprofen plus caffeine to treat tension-type headache.

Simple analgesics such as ibuprofen, aspirin, and acetaminophen have long been used in the treatment of tension-type headache. Studies of combination agents of aspirin with caffeine or acetaminophen with caffeine have also demonstrated efficacy as analgesic agents. Other evidence also suggests that caffeine may have an analgesic effect unto itself in the relief of pain. We undertook the direction of a multicenter, double-blind, placebo-controlled, parallel trial to assess the efficacy and safety of ibuprofen combined with caffeine in the treatment of tension-type headache. The study was designed to also verify the analgesic efficacy of caffeine and further assess the role of tension-type headache as a model for the study of pain.

Comparative study of a combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the treatment of migraine.

OBJECTIVE: To compare the safety and efficacy of isometheptene mucate, dichloralphenazone with acetaminophen to sumatriptan succinate for the treatment of mild-to-moderate migraine, with or without aura, when taken at the first sign of an attack. BACKGROUND: The Food and Drug Administration approved sumatriptan succinate and the combination of isometheptene mucate, dichloralphenazone with acetaminophen for the treatment of migraine. As part of the stratified treatment of migraine, those patients whose headaches are mild or moderate may benefit from nontriptan medications. Additionally, early treatment of acute migraine before the headache has become moderate or severe may improve response to treatment. METHODS: This was a multicenter, double-blind, randomized, parallel-group study to assess the safety and efficacy of the combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the early stages of a single migraine attack. Patients diagnosed with migraine, with or without aura, as defined by the International Headache Society diagnostic criteria were enrolled. RESULTS: One hundred thirty-seven patients were enrolled in the study. Data for efficacy were available for 126 patients; safety data were available for 128 patients. No statistically significant difference between the two active agents in the patient's response to treatment was demonstrated. Headache recurrence was not significantly different over the 24-hour evaluation period for those patients responding in the first 4 hours. In those with headache recurrence, it was statistically significantly more severe in those patients treated with sumatriptan succinate. Improvement in functional disability was, in general, better among those treated with isometheptene mucate, dichloralphenazone with acetaminophen. Global analysis of efficacy was similar in the two active groups. Patients treated with sumatriptan succinate were somewhat more likely to have adverse effects than the isometheptene mucate, dichloralphenazone with acetaminophen group. CONCLUSIONS: Both isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate are safe and effective when used early in the treatment of an acute migraine. Several parameters suggest that isometheptene mucate, dichloralphenazone with acetaminophen may have a slight advantage compared with sumatriptan succinate in the early treatment of mild-to-moderate migraine.

Divalproex in the long-term treatment of chronic daily headache.

OBJECTIVE: The purpose of this study was to assess the safety and efficacy of divalproex sodium in the long-term treatment of chronic daily headache. Correlations between treatment variables were assessed. BACKGROUND: Controlled and open-label trials of divalproex sodium have previously demonstrated its efficacy and safety in the treatment of migraine and chronic daily headaches. These data were primarily short-term and did not examine interaction between treatment variables. METHODS: Retrospective chart review with data extraction was conducted from headache diaries of 642 current patients under treatment with divalproex sodium for chronic daily headaches. One hundred thirty-eight of the patients were treated with only divalproex sodium. Demographic variables including age, sex, initial and final body weights, adverse events, dose of divalproex sodium, duration of treatment, and the ability to differentiate their chronic daily headache into its migraine and tension-type headache components were analyzed. Baseline and end of study headache frequency indices were obtained. RESULTS: The mean improvement was 47%, with an improvement in migraine of about 65%. At least a 50% reduction in headache frequency was reported by 93 of the 138 patients receiving treatment with only divalproex sodium. No correlation between response and age, sex, duration of treatment, and the prescribed dose of divalproex sodium was demonstrated. Adverse events occurred in approximately 35% of the patients. None were severe. Women were more likely to experience adverse effects than men. Weight gain, however, occurred less commonly in women (mean, 1.9 lbs) than in men (mean, 7 lbs). Initial body weight and age did not correlate with the weight change. CONCLUSIONS: Divalproex sodium can be used for a prolonged period as a sole agent for the successful treatment of chronic daily headache. Nearly 75% of the patients had at least a 50% reduction in headache frequency, and adverse effects occurred in approximately one third. Weight gain was negligible and hepatotoxicity did not occur during treatment periods of up to 6 years.

Acute treatment of migraine and the role of triptans.

The use of triptans has improved the ability to treat migraine successfully compared with older treatments. Speed of relief, consistency of effect, and good tolerability have been the hallmarks of these agents. All of the currently available triptans have comparable efficacy and tolerability. Variables between the agents may lead to one agent or dose form being preferred over another in various clinical scenarios. The triptans that are forthcoming may improve on these options through enhanced efficacy rates, tolerability, and headache recurrence rates. There exist increasing options for migraine treatment that may further improve the clinical effects of the older and newer triptans through early treatment of migraine at the stages of mild migraine pain, or even during the prodromal phase of the attack. Additionally, recent work suggests that mini-prophylaxis of migraine at the menses is a highly successful treatment option with the triptans. In this age of managed care, providing cost-effective treatment of headache will take on increasing importance. Techniques such as stratification of acute treatments may enhance cost-effective care, whereas ready availability of the triptans may lead to significant improvements in utilization of parameters such as office visits, emergency room treatment, and even hospitalization.

Ibuprofen plus caffeine in the treatment of tension-type headache.

BACKGROUND: The effectiveness of caffeine as an adjuvant to ibuprofen has been documented in investigations of acute pain. Our objectives were to assess this agent in the treatment of tension-type headache and to establish clinical trial methods capable of assessing this agent in comparison with various tension headache treatments. Stopwatch technology was used for measurement techniques. METHODS: A randomized, double-blind, parallel, multicenter, single-dose, placebo- and active-controlled study included 301 subjects diagnosed with tension-type headache. Treatment groups included ibuprofen and caffeine, ibuprofen alone, caffeine alone, or placebo. Subjects measured onset of relief (both time to first perceptible relief and time to meaningful relief) after taking a single oral dose of their assigned medication. Pain intensity and pain relief were rated over a 6-hour study period. Overall evaluation was made on completion of all other ratings. RESULTS: Ibuprofen and caffeine administered together provided significantly greater analgesic activity than ibuprofen alone, caffeine alone, and placebo. Ibuprofen and caffeine administered together demonstrated significantly shorter times to meaningful improvement in headache relief than ibuprofen or placebo; significantly greater total analgesia than ibuprofen alone, caffeine alone, or placebo; and significantly greater peak relief than ibuprofen alone, caffeine alone, or placebo. Significantly more subjects obtained meaningful headache relief with ibuprofen and caffeine administered together than with ibuprofen alone or placebo. More patients reported complete headache relief with ibuprofen and caffeine administered together than with ibuprofen alone, caffeine alone, or placebo. Ibuprofen and caffeine administered together was rated significantly better by patients than either ibuprofen alone, caffeine alone, or placebo. No subjects ended participation in the study early because of adverse events. CONCLUSIONS: Sensitive methods have been introduced to assess differences in analgesia among over-the-counter analgesic agents in relieving tension-type headache pain. A double-blind study with this method suggests that ibuprofen and caffeine administered together provides greater analgesic effectiveness than either component alone.

Serotonin syndrome induced by transitioning from phenelzine to venlafaxine: four patient reports.

With the use of the newer antidepressants beyond the traditional tricyclics and monoamine oxidase inhibitors, newer options in headache prophylaxis are provided as well as the potential for undesirable and even potentially life-threatening interactions between medications. In this article, four patient reports of a specific interaction--the serotonin syndrome--are presented. These events resulted from transitioning headache patients from an older antidepressant (phenelzine) to a newer antidepressant (venlafaxine).

Emergency treatment of headache.

Headache is a frequent presenting complaint in the emergency department. Once a diagnosis is established, and significant organic disease can be ruled out, relief of pain must be addressed. Referral for follow-up care and narcotic habituation is a recurrent problem for the emergency physician. This article discusses the differential diagnosis of headache, evaluation of the emergency room patient, and treatment of the patient with headache.

Migraine headache variants.

Migraine headache variants consist of the complicated migraine headache subtypes such as basilar artery migraine, migraine equivalents, and late-life migraine accompanients. Although these disorders occur infrequently, diagnosis may be more difficult. Generally, comprehensive diagnostic studies are required to rule out underlying pathogenic conditions that may present with similar symptom complexes. Standard migraine treatment is often useful in these disorders; however, migrainous variants deserve special therapeutic considerations.

Sexual headaches occurring in cluster headache patients.

A number of classifications of headache have appeared in medical and professional journals. In addition to these formal diagnostic classifications, a number of articles have addressed the relationship of sexual functioning to headache etiology, course, and prevalence. To this end, many headache specialists have developed a classification for what are termed "sexual headaches." To date, these sexual headaches have been limited to migraine and muscle contraction (tension) headache patterns. We present, for the first time, two case studies documenting the role of sexual activity in both etiology and course of cluster headache.

Treatment of headache.

Headache is the most common complaint encountered in clinical practice. Approximately 45 million people in the United States experience chronic headaches. The management of migraine headache involves both pharmacologic and nondrug therapy. Drug therapy for migraine involves the use of abortive and prophylactic agents. Abortive agents, such as ergotamine tartrate and ketoprofen, may be used to relieve the acute attack. Prophylactic therapy is focused on reducing the frequency and severity of the attacks. beta-Adrenergic blocking agents, such as propranolol, remain the primary agents for many migraine patients, although other drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), including ketoprofen, or calcium-channel blocking agents, such as verapamil, may be beneficial for many patients. For cluster headache and its variants, methysergide and corticosteroids are usually the drugs of choice. Patients with chronic cluster headache may achieve good results from long-term treatment with other therapies, including lithium carbonate, verapamil, and ketoprofen.

Migraine headache. Working for the best outcome.

Migraine is a common hereditary disorder manifested by episodic headache, irritability, and gastrointestinal upset. The condition may be triggered by dietary, environmental, psychological, or pharmacologic factors. With proper diagnosis and judicious use of abortive and prophylactic therapy, patients often obtain excellent results.