Migraine Disorders: Silberstein S

Silberstein S, Tfelt-Hansen P, Dodick DW, Limmroth V, Lipton RB, Pascual J, Wang SJ, Anonymous00408. · Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. [corrected] · Cephalalgia. · Pubmed #18294250 No free full text.

Abstract: In 1991 the Clinical Trials Subcommittee of the International Headache Society (IHS) developed and published its first edition of the Guidelines on controlled trials of drugs in episodic migraine because only quality trials can form the basis for international collaboration on drug therapy, and these Guidelines would 'improve the quality of controlled clinical trials in migraine'. With the current trend for large multinational trials, there is a need for increased awareness of methodological issues in clinical trials of drugs and other treatments for chronic migraine. These Guidelines are intended to assist in the design of well-controlled clinical trials of chronic migraine in adults, and do not apply to studies in children or adolescents.

Lewis D, Ashwal S, Hershey A, Hirtz D, Yonker M, Silberstein S, Anonymous00323, Anonymous00324. · Division of Child Neurology, Department of Pediatrics, Children's Hospital of the King's Daughters, Eastern Virginia Medical School, Norfolk, USA. · Neurology. · Pubmed #15623677 No free full text.

Abstract: OBJECTIVE: To review evidence on the pharmacologic treatment of the child with migraine headache. METHODS: The authors reviewed, abstracted, and classified relevant literature. Recommendations were based on a four-tiered scheme of evidence classification. Treatment options were separated into medications for acute headache and preventive medications. RESULTS: The authors identified and reviewed 166 articles. For acute treatment, five agents were reviewed. Sumatriptan nasal spray and ibuprofen are effective and are well tolerated vs placebo. Acetaminophen is probably effective and is well tolerated vs placebo. Rizatriptan and zolmitriptan were safe and well tolerated but were not superior to placebo. For preventive therapy, 12 agents were evaluated. Flunarizine is probably effective. The data concerning cyproheptadine, amitriptyline, divalproex sodium, topiramate, and levetiracetam were insufficient. Conflicting data were found concerning propranolol and trazodone. Pizotifen, nimodipine, and clonidine did not show efficacy. CONCLUSIONS: For children (>age 6 years), ibuprofen is effective and acetaminophen is probably effective and either can be considered for the acute treatment of migraine. For adolescents (>12 years of age), sumatriptan nasal spray is effective and should be considered for the acute treatment of migraine. For preventive therapy, flunarizine is probably effective and can be considered, but is not available in the United States. There are conflicting or insufficient data to make any other recommendations for the preventive therapy of migraine in children and adolescents. For a clinical problem so prevalent in children and adolescents, there is a disappointing lack of evidence from controlled, randomized, and masked trials.

Dodick DW, Silberstein S, Dahlöf CG. · No affiliation provided · Headache. · Pubmed #12005269 No free full text.

This publication has no abstract.

Silberstein S, Diener HC, Lipton R, Goadsby P, Dodick D, Bussone G, Freitag F, Schwalen S, Ascher S, Morein J, Greenberg S, Biondi D, Hulihan J. · Thomas Jefferson University-Neurology, Philadelphia, PA 19107, USA. · Headache. · Pubmed #18687081 No free full text.

Abstract: The term chronic daily headache refers to a heterogeneous group of headache disorders characterized by a frequency of headaches on > or = 15 days per month. Chronic migraine is a subtype of chronic daily headache. The prevalence of chronic migraine is approximately 1%. Baseline attack frequency and acute medication overuse have been identified as potential risk factors for the progression of migraine from an episodic disorder to a chronic condition. There is an unmet patient need for effective and safe treatments for patients with chronic migraine, but data from rigorous controlled trials are limited. Previous studies have demonstrated that topiramate is an effective and safe preventive treatment for episodic migraine. In addition, pilot studies have suggested the utility of topiramate for the prevention of chronic migraine. Two randomized, double-blind, placebo-controlled, multicenter trials investigating the efficacy and safety of topiramate in the treatment of patients with chronic migraine have recently been completed. This review presents comparative data from these 2 clinical trials, which suggest that topiramate at a dose of 100 mg daily is effective and generally well tolerated in chronic migraine.

Ashkenazi A, Silberstein S. · Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107, USA. · Arch Neurol. · Pubmed #18195155 No free full text.

This publication has no abstract.

Ashkenazi A, Silberstein S. · Thomas Jefferson University, Department of Neurology, Philadelphia, PA 19107, USA. · Expert Opin Pharmacother. · Pubmed #17685879 No free full text.

Abstract: Migraine in some women is associated with changes in sex hormone levels. Many women suffer from increased frequency of migraine around the time of menses. Menstrual migraine (MM) may be more severe than migraine that occurs at other times of the cycle. The pathogenesis of MM is probably related to declining estrogen levels after exposure to high levels of the hormone for several days. The acute treatment of MM is similar to that of non-menstrually-related attacks. 5-HT(1B/1D) agonists (triptans), ergots, NSAIDs, or combination analgesics may be used, although the response to some drugs may not be as robust as that of non-menstrual attacks. Women who suffer from frequent or debilitating MM attacks may benefit from perimenstrual prophylaxis that can be either hormonal or non-hormonal.

Gagne JJ, Leas B, Lofland JH, Goldfarb N, Freitag F, Silberstein S. · Department of Health Policy, Jefferson Medical College, Philadelphia, Pennsylvania, USA. · Dis Manag. · Pubmed #17590144 No free full text.

Abstract: Migraine headache is a highly prevalent, chronic, episodic disorder that is associated with high direct and indirect costs. Migraine headache impacts not only patients, but also their employers due to substantial decreases in workplace productivity. Despite the prevalence and clinical and economic burdens of migraine, no national efforts to develop and implement standardized measures of quality of care have been made. The objective of this study was to collect and report on existing quality of care measures for migraine that could be suitable for quality measurement at the health-plan level. Published literature, the Agency for Healthcare Research and Quality's National Quality Measure Clearinghouse, and resources available from quality organizations (eg, the National Committee for Quality Assurance) were examined to identify existing quality indicators that can be used to assess the quality of care delivered to migraine sufferers at the health-plan level. Among the results of the study were the following: Quality of care measures for migraine include patient-reported measures and non-patient reported, diagnosis-related, prevention-related, and treatment-related indicators. Most existing measures have been developed by the Institute for Clinical Systems Improvement or summarized and reported by the RAND Corporation. Few of these measures can be used to assess migraine quality of care at the health-plan level. In conclusion, many measures exist, but they are not intended for use at the health-plan level. Incorporation of valid and reliable quality of care measures may increase the ability of migraine disease management programs to conform to clinical care guidelines. Significant effort is needed to determine what and how to measure quality among health plans to improve the quality of care delivered to individuals with migraine.

Saper JR, Silberstein S, Dodick D, Rapoport A. · Michigan Head Pain and Neurological Institute, Ann Arbor, USA. · Headache. · Pubmed #17078853 No free full text.

Abstract: Despite a large array of currently marketed, frequently effective drugs for the acute treatment of migraine headache, comprising various classes and formulations, predictably reliable treatment for most headache types is often lacking. Dihydroergotamine mesylate (DHE) is a comparatively safe and effective therapy for migraine headache that could potentially be used for a broader range of headache types than occurs at present. The features of DHE supporting this assertion include (1) effectiveness in terminating severe, long-lasting headaches, (2) rapid onset of action, (3) very low rates of headache recurrence, (4) minimal risk of medication-overuse headache, and (5) in the nasal spray formulation, suitability for outpatients (especially patients who are very nauseated or vomiting, potentially obviating the need for an office or hospital visit for acute care). Conditions or circumstances for which there are data supporting the expanded use of DHE include menstrual migraine, migraine with central sensitization and cutaneous allodynia, medication-overuse headache, migraine recurrence, and status migrainosus. The introduction of the intranasal formulation of DHE provides both pharmacologic and patient-convenience advantages for use in migraine therapy. This article reviews the rationale for the use of DHE in these common, often difficult-to-treat migraine forms.

Dodick D, Silberstein S. · Mayo Clinic, Scottsdale, AZ 85255, USA. · Headache. · Pubmed #17078850 No free full text.

Abstract: The clinical science of migraine headache continues to evolve. Theories of the pathophysiology of migraine have progressed from the early vascular basis of migraine to more complex current theories that emphasize the centrality of neuronal dysfunction. The most recently articulated theory of migraine is the central sensitization hypothesis, which proposes that altered processing of sensory input in the brainstem, principally the trigeminal nucleus caudalis, could account for many of the temporal and symptomatic features of migraine, as well as its poor response to triptan therapy when such treatment is initiated hours after the onset of pain. Both preclinical and clinical data support the central sensitization theory. A critical clinical implication of this theory is that drugs that are capable of either aborting or arresting the process of central sensitization, most prominently dihydroergotamine, may have a unique role in the treatment of migraine. An additional, and highly practical, implication is based upon the finding that cutaneous allodynia-pain arising from innocuous stimulation of the skin, as in hair brushing or the application of cosmetics-is an easily identifiable marker of central sensitization. Thus, the presence or absence of cutaneous allodynia can be integrated into the routine clinical assessment of migraine and utilized as a determinant of treatment. Future basic and clinical research on central sensitization is likely to be of ongoing importance to the field.

Saper JR, Silberstein S. · Michigan Head Pain and Neurological Institute, Ann Arbor 48104, USA. · Headache. · Pubmed #17078849 No free full text.

Abstract: Dihydroergotamine mesylate (DHE), an ergot alkaloid, has been extensively utilized and studied in the treatment of episodic and chronic migraine. This article reviews the pharmacokinetics, pharmacodynamics, and clinical efficacy and safety of DHE, particularly in comparison to ergotamine tartrate (ET), a similar ergot alkaloid with a long history of use in the treatment of migraine. Structural differences between these 2 compounds account for clinically important distinctions in their pharmacokinetic, pharmacodynamic, and adverse event profiles. DHE is a significantly less potent arterioconstrictor than is ET, which makes it a potentially much safer drug. In addition, DHE is associated with a markedly lower incidence of medication-withdrawal headache, nausea, and vomiting than is ET. The safety and efficacy data presented here are derived from clinical trials and case series involving DHE administered by intravenous infusion, intramuscular or subcutaneous injection, or intranasal spray.

Dodick DW, Martin VT, Smith T, Silberstein S. · Department of Neurology, Mayo Clinic Scottsdale, AZ 85359, USA. · Headache. · Pubmed #15149490 No free full text.

Abstract: Triptans are not widely used in clinical practice despite their well-established efficacy, endorsement by the US Headache Consortium, and the demonstrable need to employ effective intervention to reduce migraine-associated disability. Although the relatively restricted use of triptans may be attributed to several factors, research suggests that prescribers' concerns about cardiovascular safety prominently figure in limiting their use. This article reviews clinical data--including results of clinical trials, postmarketing studies and surveillance, and pharmacodynamic studies--relevant to assessing the cardiovascular safety profile of the triptans. These data demonstrate that triptans are generally well tolerated. Chest symptoms occurring during use of triptans are usually nonserious and usually not attributed to ischemia. Incidence of triptan-associated serious cardiovascular adverse events in both clinical trials and clinical practice appears to be extremely low. When they do occur, serious cardiovascular events have most often been reported in patients at significant cardiovascular risk or in those with overt cardiovascular disease. Adverse cardiovascular events also have occurred, however, in patients without evidence of cardiovascular disease. Several lines of evidence suggest that nonischemic mechanisms are responsible for sumatriptan-associated chest symptoms, although the mechanism of chest symptoms has not been determined to date. Importantly, most of the clinical trials and clinical practice data on triptans are derived from patients without known cardiovascular disease. Therefore, the conclusions of this review cannot be extended to patients with cardiovascular disease. The cardiovascular safety profile of triptans favors their use in the absence of contraindications.

Dodick D, Lipton RB, Martin V, Papademetriou V, Rosamond W, MaassenVanDenBrink A, Loutfi H, Welch KM, Goadsby PJ, Hahn S, Hutchinson S, Matchar D, Silberstein S, Smith TR, Purdy RA, Saiers J, Anonymous00017. · Department of Neurology, Mayo Clinic Scottsdale, AZ 85259, USA. · Headache. · Pubmed #15147249 No free full text.

Abstract: BACKGROUND: Health care providers frequently cite concerns about cardiovascular safety of the triptans as a barrier to their use. In 2002, the American Headache Society convened the Triptan Cardiovascular Safety Expert Panel to evaluate the evidence on triptan-associated cardiovascular risk and to formulate consensus recommendations for making informed decisions for their use in patients with migraine. OBJECTIVE: To summarize the evidence reviewed by the Triptan Cardiovascular Safety Expert Panel and their recommendations for the use of triptans in clinical practice. PARTICIPANTS: The Triptan Cardiovascular Safety Expert Panel was composed of a multidisciplinary group of experts in neurology, primary care, cardiology, pharmacology, women's health, and epidemiology. EVIDENCE AND CONSENSUS PROCESS: An exhaustive search of the relevant published literature was reviewed by each panel member in preparation for an open roundtable meeting. Pertinent issues (eg, cardiovascular pharmacology of triptans, epidemiology of cardiovascular disease, cardiovascular risk assessment, migraine) were presented as a prelude to group discussion and formulation of consensus conclusions and recommendations. Follow-up meetings were held by telephone. CONCLUSIONS: (1) Most of the data on triptans are derived from patients without known coronary artery disease. (2) Chest symptoms occurring during use of triptans are generally nonserious and are not explained by ischemia. (3) The incidence of serious cardiovascular events with triptans in both clinical trials and clinical practice appears to be extremely low. (4) The cardiovascular risk-benefit profile of triptans favors their use in the absence of contraindications.

Sanchez del Rio M, Silberstein S. · Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. · Curr Pain Headache Rep. · Pubmed #11252151 No free full text.

Abstract: Drug selection for the acute treatment of migraine is based on comorbid disorders, coexistent diseases, and the patient's pain profile and specific needs and expectations. Patients should be instructed to tailor their treatment strategy to meet their specific needs by varying their medications according to pain intensity. This will aid in successful headache management, by increasing compliance and decreasing disability and cost.

Silberstein S, Merriam G. · Thomas Jefferson University School of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA. · Neurology. · Pubmed #10487507 No free full text.

Abstract: The normal female life cycle is associated with a number of hormonal milestones: menarche, pregnancy, contraceptive use, menopause, and the use of replacement sex hormones. All these events and interventions alter the levels and cycling of sex hormones and may cause a change in the prevalence or intensity of headache. The menstrual cycle is the result of a carefully orchestrated sequence of interactions among the hypothalamus, pituitary, ovary, and endometrium, with the sex hormones acting as modulators and effectors at each level. Estrogen and progestins have potent effects on central serotonergic and opioid neurons, modulating both neuronal activity and receptor density. The primary trigger of menstrual migraine appears to be the withdrawal of estrogen rather than the maintenance of sustained high or low estrogen levels. However, changes in the sustained estrogen levels with pregnancy (increased) and menopause (decreased) appear to affect headaches. Headaches that occur with premenstrual syndrome appear to be centrally generated, involving the inherent rhythm of CNS neurons, including perhaps the serotonergic pain-modulating systems.

Tuchman MM, Hee A, Emeribe U, Silberstein S. · Palm Beach Neurological Center, Palm Beach Gardens, Florida 33418, USA. · CNS Drugs. · Pubmed #18788838 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy and tolerability of oral zolmitriptan as a short-term preventative therapy for menstrual migraine. METHODS: This was a randomized, double-blind, parallel group, placebo-controlled, multicentre, two-phase study. The results of the second phase are reported here (the first phase evaluated zolmitriptan in the acute treatment of menstrual migraine and is reported elsewhere). Women who successfully completed phase I (with either a positive or negative outcome, and who still fulfilled the inclusion criteria) were randomized to zolmitriptan 2.5 mg oral tablet three times daily, zolmitriptan 2.5 mg twice daily or placebo three times daily. Patients were treated for three consecutive menstrual cycles, starting 2 days prior to the expected onset of menses, for 7 days in total. RESULTS: Two hundred and fifty-three patients completed phase I and were eligible for phase II. The intention-to-treat population comprised 244 patients (zolmitriptan three times daily [n = 83]; zolmitriptan twice daily [n = 80]; placebo [n = 81]). Both zolmitriptan regimens demonstrated superior efficacy versus placebo, as measured by the proportion of patients with a >or=50% reduction in the frequency of menstrual migraine attacks (zolmitriptan three times daily [58.6%], p = 0.0007 vs placebo; zolmitriptan twice daily [54.7%], p = 0.002 vs placebo; placebo three times daily [37.8%]). The mean frequency of breakthrough migraine attacks per menstrual cycle was reduced accordingly. Fewer breakthrough attacks were treated with escape medication in the zolmitriptan three times daily (61.6% of attacks; p = 0.0004 vs placebo) and twice daily (60.7%; p = 0.0055 vs placebo) treatment groups than in the placebo group (74.4%). Short-term preventative therapy with zolmitriptan was well tolerated. CONCLUSION: Zolmitriptan 2.5 mg oral tablet is effective and well tolerated as a short-term preventative therapy for menstrual migraine attacks.

Dodick DW, Silberstein S, Saper J, Freitag FG, Cady RK, Rapoport AM, Mathew NT, Hulihan J, Crivera C, Rupnow MF, Mao L, Finlayson G, Greenberg SJ. · Mayo Clinic College of Medicine, Department of Neurology, Scottsdale, AZ, USA. · Headache. · Pubmed #18052949 No free full text.

Abstract: BACKGROUND: Chronic migraine is a disabling primary chronic daily headache disorder that significantly impacts the daily activities of patients with this disorder. To our knowledge, this is the first report of a large, randomized, double-blind, placebo-controlled trial that assessed the impact of topiramate on the daily activities, emotional distress, headache-related disability, and global impression of change in patients with chronic migraine. OBJECTIVE: To assess whether topiramate 100 mg/day reduces migraine-related disability and limitations of daily activities in patients with chronic migraine. STUDY DESIGN/METHODS: Patients aged > or =18 years with chronic migraine were randomized 1 : 1 ratio to topiramate 100 mg/day or placebo. The double-blind period lasted 16 weeks. Three patient-reported outcome measures were administered: Migraine Disability Assessment, Migraine-Specific Quality of Life Questionnaire (Domains: Role Function Restrictive and Preventive and Emotional Function), and Subject's Global Impression of Change. Investigators completed a Physician's Global Impression of Change for each patient. Subject's Global Impression of Change and Physician's Global Impression of Change were completed one time, at the end of study, and measured on a 7-point scale (1 = very much improved to 7 = very much worse). The Migraine-Specific Quality of Life Questionnaire was analyzed using analysis of covariance (last observation carried forward) approach. Results were not adjusted for multiplicity. RESULTS: A total of 328 patients were randomized (topiramate, n = 165; placebo, n = 163), and 306 patients were included in the intent-to-treat population. Mean age was 38.2 years, and a majority of the patients were female (85.3%). Fifty-six percent of topiramate-treated patients vs 45% of placebo-treated patients reported >50% improvement from baseline in Migraine Disability Assessment scores (P = .074). The Migraine-Specific Quality of Life Questionnaire analysis demonstrated significant improvements at week 4 in all 3 domains, and at weeks 8 and 16 in both Role Function-Restrictive and Emotional Function domains (P < .05). Role Function-Preventive approached, but did not reach significance, at week 8 (P = .053). Seventy-five percent and 72% of topiramate-treated patients vs 61% and 59% of placebo-treated patients reported improvements on the Subject and Physician's Global Impression of Change scales (P = .025 and P = .037, respectively). CONCLUSION: Compared with placebo-treated patients, topiramate 100 mg/day appears to contribute to reductions in migraine-related limitations on daily activities and emotional distress beginning as early as week 4 and continuing up to week 16 after treatment. Physician's Global Impression of Change results are very similar with Subject's Global Impression of Change, indicating concordance between the physician's and the subject's assessment of improvement.

Tuchman M, Hee A, Emeribe U, Silberstein S. · Palm Beach Neurological Center, Palm Beach Gardens, FL 33418, USA. · CNS Drugs. · Pubmed #17140280 No free full text.

Abstract: OBJECTIVE: To determine the efficacy and tolerability of zolmitriptan 2.5 mg oral tablet as an acute treatment for menstrual migraine attacks. METHODS: This was a two-phase, multicentre, randomised, double-blind, placebo-controlled, parallel-group outpatient study (Phase I is reported here). The study was conducted at 27 sites in the USA. Eligible women were randomised (1 : 1) to receive either zolmitriptan 2.5 mg oral tablet or placebo, and instructed to acutely treat up to two menstrual migraine attacks per menstrual period for up to three menstrual cycles with a single dose of study medication. Menstrual migraine was operationally defined as an attack occurring within the time period of 2 days prior to the expected onset of menses to 5 days after the onset of menses. Participants were asked to treat migraine headaches of moderate or severe intensity only that occurred >24 hours after the end of the last migraine attack and that had not been acutely treated with other medications. Information regarding each migraine attack was recorded by patients in treatment diary cards. The primary efficacy variable was 2-hour headache response (defined as a 2-point drop on a 4-point scale) for all attacks treated. Secondary variables included 1- and 4-hour headache response rate; 1-, 2- and 4-hour headache response based on a 100 mm visual analogue scale (VAS); pain-free rate at 1, 2 and 4 hours; use of escape medication; the proportion of patients with recurrence within 24 hours of initial treatment; and tolerability. RESULTS: The intention-to-treat population comprised 334 patients (zolmitriptan [n = 174]; placebo [n = 160]). Patients treated 625 attacks with zolmitriptan and 529 attacks with placebo. Twice as many patients who took zolmitriptan achieved a 2-hour headache response compared with placebo recipients (65.7% vs 32.8%; p < 0.0001). Furthermore, a significantly higher headache response was observed with zolmitriptan than placebo at all timepoints assessed. Significantly more zolmitriptan recipients were pain-free 2 hours post-dose compared with placebo recipients (p < 0.0001). The use of escape medication was considerably lower in zolmitriptan recipients (42.6% vs 71.3%; p < 0.0001). Based on the reduction in VAS score of > or = 30 mm from baseline, significantly more zolmitriptan recipients achieved headache response compared with placebo recipients at 1, 2 and 4 hours post-dose (all p < 0.0001). Recurrence was reported in 29.1% of zolmitriptan-treated attacks versus 45.1% of placebo-treated attacks (p = 0.0009), with median time to recurrence of 8.5 and 4.0 hours, respectively. Zolmitriptan was well tolerated. CONCLUSION: Oral zolmitriptan is effective and well tolerated for the acute treatment of menstrual migraine attacks. The results are similar to those seen with zolmitriptan in studies of the general migraine population.

Silberstein S, Tepper S, Brandes J, Diamond M, Goldstein J, Winner P, Venkatraman S, Vrijens F, Malbecq W, Lines C, Visser WH, Reines S, Yuen E. · Jefferson Headache Center, Philadelphia, , PA 19107, USA. · Neurology. · Pubmed #15136680 No free full text.

Abstract: OBJECTIVE: To investigate the clinical profile of rofecoxib, a long-acting (approximately 17-hour half-life) selective cyclo-oxygenase-2 inhibitor, for the acute treatment of migraine. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted. Patients age > or =18 treated a moderate or severe migraine headache with placebo (n = 182), rofecoxib 25 mg (n = 183), or rofecoxib 50 mg (n = 192). The primary efficacy measure was headache relief (mild or no pain) 2 hours after dose. RESULTS: The proportions of patients with migraine headache relief at 2 hours after dose were 34.3% for placebo, 54.0% for rofecoxib 25 mg (p < 0.001 vs placebo), and 56.7% for rofecoxib 50 mg (p < 0.001 vs placebo). Rofecoxib 25 and 50 mg were superior to placebo in providing pain freedom at 2 hours, 24-hour sustained headache relief, and 24-hour sustained pain freedom; in reducing photophobia, phonophobia, nausea (50 mg only), and functional disability at 2 hours after dose; and in improving some quality-of-life scores over 24 hours. More patients on rofecoxib 50 mg reported adverse events (39.6%) than patients on rofecoxib 25 mg (26.8%) or placebo (23.6%) regardless of drug relatedness; however, the incidences of drug-related adverse events were similar between treatment groups. These adverse events were generally mild or moderate in severity. The most commonly reported adverse events were dry mouth, dizziness, somnolence, nausea, dyspepsia, paresthesia, and asthenia, with similar incidences between treatment groups. CONCLUSION: Rofecoxib 25 and 50 mg were effective and generally well tolerated for the acute treatment of migraine attacks.

Freitag FG, Collins SD, Carlson HA, Goldstein J, Saper J, Silberstein S, Mathew N, Winner PK, Deaton R, Sommerville K, Anonymous00267. · Diamond Headache Clinic, 467 W. Deming Place, Chicago, IL 60614, USA. · Neurology. · Pubmed #12058094 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy and safety of extended-release divalproex sodium compared with placebo in prophylactic monotherapy treatment of migraine headache. METHODS: This was a double-blind, randomized, placebo-controlled, parallel-group study. Subjects with more than two migraine headache attacks during a 4-week baseline were randomly assigned in a 1:1 ratio at each center to receive either extended-release divalproex sodium or matching placebo once daily for 12 weeks. Subjects initiated treatment on 500 mg once daily for 1 week, and the dose was then increased to 1,000 mg once daily with an option, if intolerance occurred, to permanently decrease the dose to 500 mg during the second week. Reduction from baseline in 4-week migraine headache rate was the primary efficacy variable. Migraine headaches separated by a < 24-hour headache-free interval were counted as single migraines in calculating migraine headache rates. Tolerance and safety were also evaluated. RESULTS: The mean reductions in 4-week migraine headache rate were 1.2 (from a baseline mean of 4.4) in the extended-release divalproex sodium group and 0.6 (from a baseline mean of 4.2) in the placebo group (p = 0.006); reductions with extended-release divalproex sodium were significantly greater than with placebo in all three 4-week segments of the treatment period. No significant differences were detected between treatment groups in either the overall incidence or in the incidence of any specific treatment-emergent adverse event; 8% of subjects treated with extended-release divalproex sodium and 9% of those treated with placebo discontinued for adverse events. CONCLUSION: Extended-release divalproex sodium is an efficacious, well-tolerated, safe, and easy-to-use once-a-day prophylactic antimigraine medication.

Loder E, Brandes JL, Silberstein S, Skobieranda F, Bohidar N, Wang L, Boyle D, Kolodny A, Guerra F, Santanello N, Johnson-Pratt L, Anonymous00003. · Spaulding Rehabilitation Hospital, Boston, MA, USA. · Headache. · Pubmed #11576197 No free full text.

Abstract: OBJECTIVE: To compare the proportion of patients who prefer rizatriptan orally disintegrating tablet (ODT) 10-mg to sumatriptan 50-mg tablet. BACKGROUND: Migraineurs express treatment preference based on a variety of attributes including the speed of pain relief and medication formulation. Rizatriptan ODT is an orally disintegrating formulation of rizatriptan, a selective 5-HT1B/1D receptor agonist. This study was conducted to determine patient preference between rizatriptan ODT 10-mg and sumatriptan 50-mg tablet for the acute treatment of migraine. METHODS: This was a multicenter, randomized, open-label, two-period crossover study conducted in the United States with 524 enrolled patients. Patients treated a single moderate or severe headache in each treatment period. Patients treated one migraine with either rizatriptan ODT 10-mg or sumatriptan 50-mg tablet, then treated a second migraine with the alternate therapy. Patients completed diary assessments at baseline, and 30, 45, 60, 90, and 120 minutes postdose and rated headache severity on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). At the final study visit following treatment of their second migraine, patients expressed preference for one of the two study medications by completing an interviewer-administered Global Preference Question and then responded to a self-administered series of questions to capture their most important reason for preferring one study medication over the other. Safety measurements were recorded through standard adverse experience reporting. RESULTS: Three hundred eighty-six patients treated two migraine attacks. For those patients who expressed a preference for either rizatriptan ODT or sumatriptan (n = 374), the percentage of patients who preferred rizatriptan ODT 10-mg (57%, n = 213) was significantly greater than those who preferred sumatriptan 50-mg tablet (43%, n = 161) (P<.01). For those patients who treated two migraine attacks and had drug severity measures for both attacks (n = 384), a significantly greater percentage of patients reported pain relief after taking rizatriptan ODT than sumatriptan at the 45- and 60-minute time points (38% versus 29% and 58% versus 49%, respectively) (P<.01). In addition, a significantly greater percentage of patients taking rizatriptan ODT reported a pain-free status at the 60- and 120-minute time points (23% versus 17% [P<.05] and 60% versus 52% [P<.01], respectively). Both rizatriptan ODT and sumatriptan were well tolerated. CONCLUSIONS: A significantly greater proportion of patients preferred rizatriptan ODT 10-mg to sumatriptan 50-mg tablet for the acute treatment of migraine. Efficacy and safety data are consistent with the preference findings.

Newman L, Mannix LK, Landy S, Silberstein S, Lipton RB, Putnam DG, Watson C, Jöbsis M, Batenhorst A, O'Quinn S. · St. Luke's-Roosevelt Hospital Center, Headache Institute, New York, NY 10019, USA. · Headache. · Pubmed #11264684 No free full text.

Abstract: OBJECTIVE: To determine the efficacy of naratriptan 1-mg and 2.5-mg tablets twice daily compared with placebo as short-term prophylaxis of menstrually associated migraine. BACKGROUND: Approximately 60% of women with migraine report headaches associated with their menstrual cycles. Results from an open-label study suggest that short-term administration of sumatriptan is useful in the prophylaxis of menstrually associated migraine. METHODS: A randomized, double-blind, three-arm, parallel-group, placebo-controlled study was conducted in women aged 18 years or older with a history of migraine with or without aura, as defined by the International Headache Society, of at least 6 months. Two dose strengths of naratriptan (1 mg, 2.5 mg) or identical-appearing placebo tablets (1:1:1) were administered twice daily for 5 days starting 2 days prior to the expected onset of menses across four perimenstrual periods. End points included the number of menstrually associated migraines, total migraine days, peak headache severity, lost work/activity time, migraine-related quality of life, and incidence of adverse events. RESULTS: Overall, the intent-to-treat population comprised 206 women (naratriptan 1 mg, n = 70; naratriptan 2.5 mg, n = 70, and placebo, n = 66); 171 women treated four perimenstrual periods. Significantly more perimenstrual periods per subject treated with naratriptan, 1 mg, were headache-free compared with placebo (50% versus 25%, P =.003). Naratriptan, 1 mg, significantly reduced the number of menstrually associated migraines (2.0 versus 4.0, P <.05) and menstrually associated migraine days (4.2 versus 7.0, P <.01) compared with placebo. More patients treated with naratriptan, 1 mg, were headache-free across all treated perimenstrual periods compared with placebo (23% versus 8%). No difference in headache severity was observed in breakthrough headaches. The incidence and severity of adverse events was similar across treatment groups. Naratriptan, 2.5 mg, was not statistically superior to placebo for any measure. CONCLUSIONS: Naratriptan, 1 mg, with tolerability similar to placebo, is an effective, short-term, prophylactic treatment for menstrually associated migraine.

Silberstein S, Mathew N, Saper J, Jenkins S. · Thomas Jefferson University School of Medicine, Philadelphia, PA, USA. · Headache. · Pubmed #10849039 No free full text.

Abstract: OBJECTIVE: To assess the safety and efficacy of botulinum toxin type A (BOTOX; Allergan, Inc) in the prevention of migraine. BACKGROUND: Current migraine preventive therapies are often unsatisfactory because of their limited efficacy, adverse effects, and drug interactions. Botulinum toxin type A injections often reduce the pain associated with conditions such as cervical dystonia, achalasia, rectal fissures, and myofascial pain syndrome. An open-label, noncontrolled study of botulinum toxin type A suggested benefits for patients with migraine. DESIGN AND METHODS: This was a double-blind, vehicle-controlled study of 123 subjects with a history of two to eight moderate-to-severe migraine attacks per month, with or without aura. Participants were randomized to receive single administrations of vehicle or botulinum toxin type A, 25 U or 75 U, injected into multiple sites of pericranial muscles at the same visit. During a 1-month baseline period and for 3 months following injection, subjects kept daily diaries in which they recorded migraine frequency, migraine severity, and the occurrence of migraine-associated symptoms. RESULTS: Compared with vehicle treatment, subjects in the 25-U botulinum toxin type A treatment group showed significantly fewer migraine attacks per month, a reduced maximum severity of migraines, a reduced number of days using acute migraine medications, and reduced incidence of migraine-associated vomiting. Both the 25-U and 75-U botulinum toxin type A groups were significantly better than the vehicle group on subject global assessment. Botulinum toxin A treatment was well tolerated, with only the 75-U treatment group exhibiting a significantly higher rate of treatment-related adverse events than vehicle. CONCLUSIONS: Pericranial injection of botulinum toxin type A, 25 U, was found to be a safe treatment that significantly reduced migraine frequency, migraine severity, acute medication usage, and associated vomiting.

Leas BF, Gagne JJ, Goldfarb NI, Rupnow MF, Silberstein S. · Department of Health Policy, Jefferson Medical College, Philadelphia, Pennsylvania, 19107, USA. · Popul Health Manag. · Pubmed #18942925 No free full text.

Abstract: Quality of care measures are increasingly important to health plans, purchasers, physicians, and patients. Appropriate measures can be used to assess quality and evaluate improvement and are necessary components of pay-for-performance programs. Despite the broad scope of activity in the development of quality measures, migraine headache has received little attention. Given the enormous costs associated with migraine, especially in terms of lost productivity and preventable health care utilization, health plans could gain from a structured approach to measuring the quality of migraine care their beneficiaries receive. A potential migraine quality measurement set was developed through a review of migraine care literature and guidelines, interviews with leaders in migraine care, health care purchasing, and managed care, and the assembly of an advisory board. The board discussed candidate measures and established consensus on a testable measurement set. Twenty measures were developed, focused primarily on diagnosis and utilization. Areas of utilization include physician visits, emergency department visits, hospitalizations, and imaging. Use of both acute and preventive medications is included. More complex aspects of migraine care are also addressed, including triptan overuse, the relationship between acute and preventive medications, and follow-up after emergency department visits. The measures are currently being tested in health plans to assess their feasibility and value. A compelling case can be made for the development of migraine-specific quality measures for health plans. This effort to develop and test a starter set of measures should lead to new and innovative efforts to assess and improve quality of care for migraineurs.

Piovesan EJ, Sobreira CF, Scola RH, Lorenzoni PJ, Lange MC, Werneck LC, Smith D, Silberstein S. · Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, PR, Brazil. · Arq Neuropsiquiatr. · Pubmed #18392420 links to  free full text

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Silberstein S, Saper J, Berenson F, Somogyi M, McCague K, D'Souza J. · Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. · Neurology. · Pubmed #18268247 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy, safety, and tolerability of oxcarbazepine (1,200 mg/day) vs placebo as prophylactic therapy for patients with migraine headaches. METHODS: This multicenter, double-blind, randomized, placebo-controlled, parallel-group trial consisted of a 4-week single-blind baseline phase and a 15-week double-blind phase consisting of a 6-week titration period, an 8-week maintenance period, and a 1-week down-titration period, after which patients could enter a 13-week open-label extension phase. During the 6-week titration period, oxcarbazepine was initiated at 150 mg/day and increased by 150 mg/day every 5 days to a maximum tolerated dose of 1,200 mg/day. The primary outcome measure was change from baseline in the number of migraine attacks during the last 28-day period of the double-blind phase. RESULTS: Eighty-five patients were randomized to receive oxcarbazepine and 85 to receive placebo. There was no difference between the oxcarbazepine (-1.30) and placebo groups in mean change in number of migraine attacks from baseline during the last 28 days of double-blind phase (-1.74; p = 0.2274). Adverse events were reported for 68 oxcarbazepine-treated patients (80%) and 55 placebo-treated patients (65%). The majority of adverse events were mild or moderate in severity. The most common adverse events (>or=15% of patients) in the oxcarbazepine-treated group were fatigue (20.0%), dizziness (17.6%), and nausea (16.5%); no adverse event occurred in more than 15% of the placebo-treated patients. CONCLUSIONS: Overall, oxcarbazepine was safe and well tolerated; however, oxcarbazepine did not show efficacy in the prophylactic treatment of migraine headaches.