Consistency of response to sumatriptan/naproxen sodium in a placebo-controlled, crossover study.

Two identical randomized, placebo-controlled, crossover studies were conducted to evaluate consistency of response to sumatriptan/naproxen sodium 85/500 mg (S/NS) over four attacks in adults with migraine. Patients were instructed to treat within 1 h of pain onset while pain was mild. Co-primary end-points were pain-free response at 2 h (2hPF) and 24-h sustained pain-free response (24hSPF) calculated as percentages of all attacks. In Study 1, 570 patients treated 1693 attacks with S/NS and 424 with placebo. In Study 2, 565 patients treated 1678 attacks with S/NS and 422 with placebo. Compared with placebo, S/NS conferred higher 2hPF rates (Study 1: S/NS 52%, placebo 25%; Study 2: S/NS 50%, placebo 20%; both P < 0.001) and higher 24hSPF rates (Study 1: S/NS 37%, placebo 17%; Study 2: S/NS 34%, placebo 12%; both P < 0.001). 2hPF was reported in at least two of the first three S/NS-treated attacks in 55.0% of patients in Study 1 and 52.1% of patients in Study 2. 24hSPF was reported in at least two of the first three S/NS-treated attacks in 35.7% of patients in Study 1 and 32.6% of patients in Study 2. The incidences of any adverse event and of specific adverse events were low and generally similar between S/NS and placebo.

Comparison of rizatriptan and other triptans on stringent measures of efficacy.

OBJECTIVE: To compare the efficacy of oral rizatriptan 10 mg with oral doses of sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures. METHODS: Retrospective analysis of data from five randomized, placebo-controlled, double-masked clinical trials in which oral rizatriptan was directly compared with oral sumatriptan 100 mg (n = 772), 50 mg (n = 1116), 25 mg (n = 1183), naratriptan 2.5 mg (n = 413), and zolmitriptan 2.5 mg (n = 580) for the acute treatment of a moderate or severe migraine attack. OUTCOME MEASURES: Percentage of patients pain-free at 2 hours, symptom-free at 2 hours (no pain, nausea, photophobia, phonophobia, vomiting, or functional disability), 24-hour sustained pain-free (no headache at 2 hours, no recurrence, and no additional antimigraine medications for 24 hours). RESULTS: More patients taking rizatriptan 10 mg were pain-free at 2 hours than were patients taking sumatriptan 100 mg (40% vs 33%, p = 0.019), sumatriptan 50 mg (40% vs 35%, p = 0.009), sumatriptan 25 mg (38% vs 27%, p < 0.001), naratriptan 2.5 mg (45% vs 21%, p < 0.001), and zolmitriptan 2.5 mg (43% vs 36%, p = 0.041). More patients taking rizatriptan 10 mg were symptom-free at 2 hours than were patients taking sumatriptan 100 mg (31% vs 22%, p = 0.002), sumatriptan 50 mg (33% vs 28%, p = 0.003), sumatriptan 25 mg (33% vs 24%, p < 0.001), naratriptan 2.5 mg (30% vs 11%, p < 0.001), and zolmitriptan 2.5 mg (31% vs 24%, p = 0.042). More patients taking rizatriptan 10 mg had a 24-hour sustained pain-free response than did patients taking sumatriptan 100 mg (27% vs 23%, p = 0.112), sumatriptan 50 mg (30% vs 26%, p = 0.015), sumatriptan 25 mg (27% vs 20%, p = 0.005), naratriptan 2.5 mg (29% vs 17%, p = 0.004), and zolmitriptan 2.5 mg (32% vs 24%, p = 0.013). CONCLUSION: Oral rizatriptan 10 mg was more effective than oral sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures of pain-free response at 2 hours, symptom-free response at 2 hours, and 24-hour sustained pain-free response.

Optimizing the dose of zolmitriptan (Zomig, 311C90) for the acute treatment of migraine. A multicenter, double-blind, placebo-controlled, dose range-finding study. The 017 Clinical Trial Study Group.

This study investigated the efficacy of zolmitriptan (Zomig, formerly 311C90) in acute migraine therapy. Patients with a history of migraine were randomized in a double-blind, multicenter, placebo-controlled, dose range-finding study of oral zolmitriptan 1, 2.5, 5, or 10 mg versus placebo for the treatment of a severe or moderate migraine headache. Patients with persistent or recurrent headache 4 to 24 hours after the initial dose, who did not take escape medication, were eligible to receive a second blinded dose of either zolmitriptan or placebo. Of 1,144 patients treated, 999 evaluable patients completed the study. The headache response rates with zolmitriptan doses > or = 2.5 mg were 44 to 51% at 1 hour, 65 to 67% at 2 hours, and 75 to 78% at 4 hours (all significantly superior to placebo). Also, zolmitriptan effectively relieved migraine-associated symptoms such as nausea, photophobia and phonophobia, and reduced activity impairment. Rates of headache recurrence, headache persistence, and use of escape medication were lower with zolmitriptan doses > or = 2.5 mg than with placebo. In patients with persistent or recurrent headache, a second zolmitriptan dose effectively treated both headache and nonheadache symptoms. Zolmitriptan was well tolerated, with a lower incidence of adverse events being reported with doses < or = 2.5 mg than with those > or = 5 mg. Zolmitriptan is a well tolerated and effective acute migraine therapy providing rapid relief of migraine headache within 1 hour. A clear dose-response relationship between efficacy and tolerability suggests that 2.5 mg is the optimal initial dose for the acute treatment of a migraine attack.

Current options for the prevention and treatment of migraine.

BACKGROUND: Migraine is a common condition affecting approximately 18% of women and 6% of men in the United States. The goals of managing migraine are 2-fold: to prevent attacks from occurring and to effectively and rapidly end them when they do occur. OBJECTIVE: This article reviews the acute and prophylactic treatment of migraine. METHODS: Information for inclusion in this review was identified through a search of MEDLINE from 1995 to the present. Search terms included migraine, acute treatment, prophylactic treatment, preventive treatment, and individual drug names. RESULTS: Preventive measures for migraine include lifestyle changes (eg, avoiding migraine triggers and maintaining regular sleep, eating, and work habits) and drug therapy. Beta-blockers, calcium channel blockers, tricyclic antidepressants, and anticonvulsants are among the more common drug classes used for migraine prophylaxis, but preventive therapy must be individualized, taking into account efficacy, potential adverse effects, co-existing medical conditions, and drug costs. Many medications are available for the acute treatment of migraine, including over-the-counter analgesics and prescription drugs. Of the latter, the 5-hydroxytryptamine(1B/1D)-receptor agonists, or triptans, are the most recently introduced class. Each of the 4 available triptans (sumatriptan, zolmitriptan, naratriptan, and rizatriptan) is effective in ending a migraine attack, but comparative trials have shown differences between individual drugs in the time to pain relief and the percentage of patients who obtain pain relief. CONCLUSIONS: Medications to prevent or reduce the frequency of migraine tend to be less specific and effective than medications for the acute treatment of migraine. As a class, triptans are generally well tolerated and may be considered drugs of choice for the acute treatment of moderate to severe migraine.

Cost of migraine management: a pharmacoeconomic overview.

Migraine is a chronic, sometimes debilitating, condition that tends to afflict young people who are otherwise healthy and productive. Because diagnostic criteria and effective treatment modalities have not been well taught to physicians, the condition is often undiagnosed, misdiagnosed, and mismanaged, causing unnecessary pain, hardship to the individual, disability, loss of productivity, and increased expense to the healthcare system. This paper discusses a rational approach to the behavioral and pharmacologic treatment of migraine, highlighting the relative costs of preventive and acute care therapies. Several cases are presented to illustrate how the costs of inefficiently managed migraine therapy can be decreased even by using medications that have a higher per-dose cost, as they decrease the pain and disability and actually lower the total cost of managing the patient with migraine.

Comparative aspects of triptans in treating migraine.

Triptans, beginning with sumatriptan, have revolutionized the treatment of migraine. New triptans in several formulations will soon become available in the United States. Although the similarities of these 5-hydroxytryptamine (5-HT) 1B/1D receptor agonists outweigh their differences, important differences in pharmacokinetics and clinical responses do exist. Subcutaneous sumatriptan has the most rapid onset of action and greatest efficacy but the most adverse effects. Intranasal sumatriptan also has rapid onset of action, but at 2 hours its efficacy is comparable to that of oral zolmitriptan. Of the oral triptans, rizatriptan seems to have the greatest early efficacy. Both rizatriptan and zolmitriptan are now available as rapidly dissolving wafers. Almotriptan, the newest of the triptans, has a response rate similar to that of oral sumatriptan and may produce fewer adverse effects. Naratriptan and frovatriptan, with their slow onset, high tolerability, and long half-lives, may have a role in aborting prolonged migraine attacks and in headache prevention. Eletriptan at higher doses (80 mg) has a response rate approaching that of rizatriptan but may be limited by potential side effects. The many triptans available offer the opportunity to individualize migraine treatment, depending on the patient's attack characteristics, tolerance, and preferences.

Headaches and papilledema secondary to dural arteriovenous malformation.

A 21-year-old developed progressive headaches and pulsatile tinnitus. He was found to have papilledema and a pulsatile bruit. A dural arteriovenous malformation was not recognized on brain CT or MRI, but was well documented on magnetic resonance angiography and cerebral angiography. Dural malformations draining into the superior sagittal sinus can cause increased intracranial venous pressure and secondarily increase intracranial pressure even without a mass effect.

Cost considerations in headache treatment. Part 1: Prophylactic migraine treatment.

Effective migraine treatment is clearly the most cost-effective in terms of both direct and indirect costs. Patient education, behavior changes, and prudent medication selection can minimize costs. Low-dose aspirin may reduce headache frequency. Among the antidepressant medications used, amitriptyine 25 mg, 3 qhs ($4.16/month) and doxepin 25 mg, 3 qhs ($10.50/month) remain the standard. Imipramine (25 mg, 3 qhs ($3.75/month) is very inexpensive and should replace nortriptyline 25 mg, 3 qhs ($64.29/month) as a second-line agent. The specific serotonin reuptake inhibitors are expensive and have no proven effect for migraine prevention. Propranolol 80 mg bid ($7.80/month) is inexpensive and frequently a good choice among beta-blockers. Atenolol 100 mg qd ($27.50/month) is less expensive than long-acting propranolol 160 mg ($35.56/month) and nadolol 120 mg qd ($43.68/month) with equivalent effectiveness. It is thus recommended as the long-acting beta-blocker of choice. Sustained-release preparations of verapamil 240 mg qd ($31.98/month) are twice the cost and less well-absorbed than the standard preparation of 120 mg bid ($17.62/month). Better information is needed concerning effectiveness and optimal dosing of some older low-cost medications in the preventive treatment of migraine.

Oral narcotic protocol to reduce narcotic injections in refractory migraine patients.

Refractory headache patients who require narcotic injections for acute attacks frequently utilize health care facilities. The experience is often unpleasant and costly to the patient and health care system. We have developed an oral narcotic protocol for home administration. The patient starts with an antiemetic suppository, followed in 30 minutes by oral metoclopramide. After controlling nausea and vomiting, the patient administers a high dose of oral narcotic plus a hypnotic. The dosing of the narcotic analgesics incorporates seldom-used, but well-published pharmacokinetics. This protocol allows the patient to successfully treat a severe headache without using a health care facility. Eleven patients in our practice were prescribed the oral narcotic protocol. Their need for narcotic injections at our office or emergency department was monitored for up to 1 year before and after the start of the protocol. Combined office visits were reduced from 81 to 53 (34.6%) and emergency department visits from 47 to 26 (44.7%). An annual cost savings of $1960 for office visits and $3024 for emergency department visits was realized. This was offset by an oral narcotic protocol medication cost of only $392. This treatment method has been well accepted by patients and has proven to be a safe and cost-effective approach to treating refractory migraine patients.

Cost considerations in headache treatment. Part 2: Acute migraine treatment.

Today's physician has many useful medication options available for acute migraine treatment. There is a wide cost range among these drugs and today's health care environment demands that cost be factored into the decision process. Effective migraine abortive treatment decreases the costs of repeat dosing and disability. Early use of migraine abortive medication can increase its rapidity of action and effectiveness. Adjunctive medication such as metoclopramide ($0.10) is inexpensive and may improve the effectiveness of the primary abortive medication. Over-the-counter medications such as aspirin ($0.02/325 mg), Excedrin ($0.09/tablet), ibuprofen ($0.04/200 mg), or naproxen sodium ($0.09/220 mg) are inexpensive and effective. "Triple therapy" combining metoclopramide, a nonsteroidal anti-inflammatory agent, and an ergotamine preparation may improve tolerance and effectiveness of the ergot. Locally compounded dihydroergotamine nasal spray is inexpensive ($0.78/1 mg spray). The cost of using oral sumatriptan can be almost halved by prescribing half of a 50-mg tablet. Emergency department services are expensive. Huge cost savings occur through self-controlled administration of oral, rectal, or even intramuscular narcotic medications. Oral narcotic agents such as hydromorphone ($0.42/4 mg) and meperidine ($0.92/200 mg) are generally used in inadequate doses to be effective for severe migraine. Guidelines are give for more effective use of these agents. Sophisticated comparative studies are needed to evaluate, not only the direct costs of medications, but all costs of treatment of an acute migraine attack, as well as indirect costs to the patient, family, and society.

Venlafaxine extended release (XR) for the prophylaxis of migraine and tension-type headache: A retrospective study in a clinical setting.

OBJECTIVE: To assess the efficacy of extended-release venlafaxine in the prophylaxis of migraine and chronic tension-type headache. BACKGROUND: Venlafaxine, a structurally novel antidepressant, is a selective serotonin-norepinephrine reuptake inhibitor. This study is the first to test the effects of extended-release venlafaxine on headaches. METHODS: Patients were evaluated on a retrospective basis. Fifty-six patients with chronic tension-type headache and 114 patients with migraine were prescribed extended-release venlafaxine. Nearly all the study subjects had been resistant to several previous preventive medications. Patients took venlafaxine for an average of 6 months with a median dose of 150 mg (range, 37.5 to 300 mg). RESULTS: The mean frequency of headaches in the group with chronic tension-type headache fell from 24.0 to 15.2 per month (P <.0001). The group with migraine showed a reduction from 16.1 to 11.1 headaches per month (P <.0001). The medicine was well tolerated. CONCLUSIONS: This trial indicates that extended-release venlafaxine has potential in headache prophylaxis based on its efficacy and safety profile. We recommend a double-blind, placebo-controlled study to further assess the role of extended-release venlafaxine in headache prevention.

Cardiac risk factors and the use of triptans: a survey study.

OBJECTIVE: To describe current practice in triptan use. BACKGROUND: Triptans are effective migraine treatments that cause chest symptoms in some patients. True cardiac ischemia is rare. Design.-Headache specialists and family practitioners completed questionnaires regarding the times when triptans are contraindicated, obtaining electrocardiograms (ECGs), and giving the first dose in the office. RESULTS: Sixty-five headache specialists and 67 family practitioners responded. Headache specialists saw an average of 36.3 patients with headache per week. Family practitioners saw an average of 7.2. Family practitioners and headache specialists had similar opinions regarding the age at which triptans were contraindicated with various numbers of risk factors. Sixty-one percent of headache specialists and 50% of family practitioners would not use a triptan at any age for patients with more than three risk factors (P = NS). Ten percent of headache specialists obtained an ECG for all patients being prescribed triptans, while no family practitioners did (P =. 008). Ten percent of both family practitioners and headache specialists never obtained an ECG, even with multiple cardiac risk factors. Headache specialists obtained ECGs more often than family practitioners (P <.002 for one to three risk factors). Family practitioners were more likely to give the first dose of the triptan in the office regardless of cardiovascular risk (58% versus 20%, P <. 001). Forty-five percent of headache specialists and 2% of family practitioners never gave the first dose in the office (P <.001). Family practitioners gave the first dose in the office more readily than headache specialists in patients with no risk factors (P =.001), but not for one or more risk factors. CONCLUSIONS: No consensus exists among family practitioners or headache specialists about when to avoid using a triptan due to excessive cardiac risk factors, when to obtain an ECG prior to using a triptan, and when to give the first dose of a triptan in the office. Headache specialists are more likely to obtain ECGs, whereas family practitioners are more likely to give the first dose of a triptan in the office.

Rizatriptan tablet versus wafer: patient preference.

After taking both conventional oral rizatriptan tablets and oral disintegrating rizatriptan tablets in the treatment of migraine with or without aura, patients were permitted to select their formulation preference. All adult patients who had requested continuation of rizatriptan during a 6-month period were included in the study. Of the 367 patients studied, 188 selected the oral disintegrating tablet, while 179 preferred the conventional tablet. Although individual patients had strong preferences for one preparation over the other, no group preference was found.

Migraine preventive medications: a reappraisal.

Newer acute care migraine medications demonstrate improved rapidity of action, consistent effectiveness, excellent safety profiles, and rarely cause rebound headaches. Their use could decrease the need for migraine-preventive medication. The present analysis derives a formula that can be used by practitioners to determine the cost-effectiveness of various migraine-preventive medications relative to selected acute-care medications. We propose a measure called the cost-equivalent number (CEN), the number of headaches per month at which the cost of the preventive medication equals the cost savings in acute-care treatment realized by using the preventive medication. The use of the CEN individualizes the decision of whether to use a migraine-preventive medication, weighing both the efficacy and cost of the preventive medication against the cost of the acute-care medication. A CEN lower than the migraine frequency suggests that use of a preventive medication will be cost-effective.

Validity and reliability of the migraine-specific quality of life questionnaire (MSQ Version 2.1).

OBJECTIVE: To assess the scaling properties, reliability, and validity of the revised Migraine-Specific Quality of Life Questionnaire (MSQ) (Version 2.1) BACKGROUND: The MSQ is a disease-specific, quality-of-life instrument with three hypothesized scales that has been developed, tested, and revised. METHODS: The study used a multicenter, nondrug, prospective, parallel group, quasi-experimental design. Patients with migraine were recruited at outpatient headache specialty practices and were administered the MSQ, the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and migraine symptom questionnaires at baseline, 4 weeks, and 12 weeks. Internal consistency (Cronbach alpha) and 4-week test-retest reproducibility (intraclass correlation coefficients) were estimated to assess reliability. Construct validity was assessed using an adaptation of the Campbell and Fiske multitrait-multimethod approach and by correlating MSQ scores with symptom measures. RESULTS: A total of 267 subjects enrolled in the trial. The criteria for summated rating scales were all met. The internal consistency coefficients ranged from 0.86 to 0.96, and the intraclass correlation coefficients ranged from 0.57 to 0.63 across the three dimensions. As anticipated, the MSQ dimensions had low-to-modest correlations with the two component scores of the SF-36 and were modestly to moderately correlated with migraine symptoms. CONCLUSIONS: The MSQ is a reliable instrument in the assessment of quality of life for patients with migraine with items that can be summed without weights. The MSQ has demonstrated evidence of construct validity.