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Consensus Statements as Topic↗
Biomedical subjects
David Dodick
Publications and source records attributed to David Dodick.
Oral sumatriptan for the acute treatment of probable migraine: first randomized, controlled study.
OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan tablets in adults who meet International Headache Society (IHS) criteria for probable migraine but who do not meet IHS criteria for migraine with or without aura. BACKGROUND: Headaches with some but not all of the features of migraine meet criteria for probable migraine, a form of migraine recognized by the IHS. Probable migraine attacks are also prevalent and frequently underdiagnosed. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled, parallel-group study. Adults (18 to 65 years) with a 1-year history of headaches that met 2004 IHS criteria for probable migraine without aura (same operational definition as 1988 IHS migrainous disorder) were eligible for enrollment. All patients were triptan- and ergot-naïve and had never been diagnosed with migraine. Patients were randomized in a 1:1:1:1 fashion to receive sumatriptan 25, 50, or 100 mg conventional tablets or matching placebo and were instructed to treat a single moderate or severe probable migraine attack. A post hoc analysis was conducted to evaluate the population of patients who achieved headache relief sustained throughout the immediate posttreatment period. Patients who reported relief within 2 hours and subsequently lost headache relief within 4 hours were considered nonresponders. RESULTS: At 2 hours, more patients treated with sumatriptan achieved headache relief, the primary efficacy measure, compared with placebo, but differences only approached statistical significance for 100 mg (P= .053). The 2-hour headache relief rate in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. The time to use of rescue was significantly shorter in the placebo group compared with the sumatriptan 100 mg group (P= .002). The time to use of rescue in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. More patients treated with placebo (22%) lost headache relief within 4 hours compared with patients treated with sumatriptan 25 mg (17%), 50 mg (14%), or 100 mg (7%). A post hoc analysis demonstrated that at 2 hours, headache relief sustained through 4 hours (S 0-4 hours) was achieved in 44%, 49%, and 57% of patients treated with sumatriptan 25, 50, and 100 mg, respectively, compared with 34% of patients treated with placebo (P < .05 for sumatriptan 50 and 100 mg vs. placebo). All doses of sumatriptan were well tolerated and no serious adverse events were reported. CONCLUSION: These results suggest that oral sumatriptan may be effective and is well tolerated for the acute treatment of probable migraine without aura, however, the difference between sumatriptan and placebo was not statistically significant for the a priori defined primary endpoint.
Acute Disease↗
Central sensitization theory of migraine: clinical implications.
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.
Analgesics, Non-Narcotic↗
Evidence-based understanding of medication-overuse headache: clinical implications.
This article discusses the problem of medication-overuse headache from a variety of perspectives, based on the best available evidence. This presentation clarifies the definition of the disorder, distinguishing it from alternative terminology, and describes its epidemiology, natural history, and clinical course. Antimigraine medications are believed to differ in their relative liability to contribute to the development of medication-overuse headache. Patients most at risk of developing medication-overuse headache need to be identified so that appropriate preventive measures can be initiated.
Analgesics↗
DHE in the pharmacotherapy of migraine: potential for a larger role.
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.
Analgesics, Non-Narcotic↗
Removing barriers to appropriate migraine treatment: formulary limitations and triptan package size.
The main goals in the pharmacologic management of migraine headache are to avert or relieve debilitating pain, prevent escalating acute medication use, and improve day-to-day functioning. This review will examine the evidence supporting the early use of acute medication, usually when pain is mild, to enhance patient outcomes. We will also discuss imposed quantity limits as a practical impediment to the implementation of this strategy in the managed care setting, and will identify strategies for overcoming this barrier to effective care. Quantity limits imposed on triptan therapy by health plans can hinder the optimal acute treatment of migraine. A standard triptan quantity limit sufficient to permit early migraine treatment and a movement by manufacturers to provide blister packs consistent with a standard quantity limit should reduce patients costs, permit brand mobility when appropriate, and bolster long-term cost effectiveness by removing an important impediment to the use of triptans when they are most effective, early in the migraine attack when pain is often still mild.
Drug Packaging↗
Management of chronic daily headache: challenges in clinical practice.
Chronic daily headache (CHD) refers to a category of headache disorders that are characterized by headaches occurring on more than 15 days per month. This category is subdivided into long- and short-duration (>4 or <4 hours) CDH disorders based on the duration of individual headache attacks. Examples of long-duration CDH include transformed migraine (TM), chronic migraine (CM), new daily persistent headache (NDPH), acute medication overuse headache, and hemicrania continua (HC). The goal of this review is to enable clinicians to accurately diagnose and effectively manage patients with long-duration CDH. Patients with CDH often require an aggressive and comprehensive treatment approach that includes a combination of acute and preventive medications, as well as nondrug therapies.
Headache Disorders↗
Speed of onset, efficacy and tolerability of zolmitriptan nasal spray in the acute treatment of migraine: a randomised, double-blind, placebo-controlled study.
INTRODUCTION: Migraine is a common, disabling condition that has a significant impact on patients and relatives, and is a considerable economic burden on society. Migraine patients want fast-acting treatments with high efficacy. Previous studies have demonstrated that orally administered formulations of zolmitriptan are rapidly and highly effective in the acute treatment of migraine. The objective of this study was to assess the efficacy, speed of onset and tolerability of the nasal spray formulation of zolmitriptan in migraine treatment. METHODS: This multicentre, randomised, double-blind study recruited 2122 patients (aged 18-65 years) who had an established diagnosis of migraine (according to International Headache Society criteria), with or without aura. Patients were randomised to receive zolmitriptan 5mg nasal spray or placebo to treat up to two migraine attacks within 15 minutes of headache pain becoming moderate or severe. The primary endpoint was headache response (reduction in migraine pain from severe/moderate to mild/none) at 2 hours, 1 hour, 30 minutes and 15 minutes post-dose (analysed using a step-down approach). Secondary endpoints included headache response at 4 hours, pain-free rates at 30 minutes and 1, 2 and 4 hours, and sustained headache response and pain-free status at 24 hours post-dose. RESULTS: The headache response rate at 2 hours post-dose was 66.2% for the zolmitriptan group, compared with 35.0% for the placebo group (p < 0.001). Zolmitriptan nasal spray also produced significantly higher headache response rates than placebo at all earlier timepoints assessed, starting as early as 15 minutes post-dose (p < 0.001). Similar results were obtained for the analysis of the first attack. Significantly higher pain-free rates were obtained with zolmitriptan nasal spray, compared with placebo, from 15 minutes post-dose onward (p < 0.005). Zolmitriptan nasal spray was also significantly superior to placebo for headache response at 4 hours, sustained headache response at 24 hours and sustained pain-free rate at 24 hours. Zolmitriptan nasal spray was well tolerated, with most adverse events being of short duration and mild or moderate intensity. CONCLUSIONS: Zolmitriptan nasal spray is highly effective in the acute treatment of migraine and has a very fast onset of action, producing significant headache response and pain-free rates as early as 15 minutes post-dose (the earliest assessment in this study). In addition to the very fast onset of action, zolmitriptan nasal spray produced significantly higher sustained headache response and pain-free rates at 24 hours post-dose compared with placebo. These desirable efficacy outcomes were combined with good tolerability.
Administration, Intranasal↗
Consensus statement: cardiovascular safety profile of triptans (5-HT agonists) in the acute treatment of migraine.
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.
Acute Disease↗
Chronic daily headache: a rational approach to a challenging problem.
Chronic daily headache (CDH) is a significant public health problem with 3 to 5% of the population worldwide experiencing daily or near-daily headaches. Patients with CDH can be particularly challenging, and clinicians require a systematic approach to help guide investigations and management. The revised 2004 International Headache Society Classification Criteria introduces formalized criteria for several CDH disorders including chronic migraine and medication overuse headache as well as new daily persistent headache, hemicrania continua, hypnic headache, and SUNCT syndrome. Medication overuse is common in patients with CDH who present to physicians. Familiarity and comfort with drug-withdrawal and detoxification strategies is therefore essential. Patients with chronic migraine and chronic cluster experience significant disability and diminished quality of life. The ability to manage these patients effectively is a rewarding clinical experience.
Adult↗
How does almotriptan compare with other triptans? A review of data from placebo-controlled clinical trials.
Almotriptan, the new selective 5-HT1B/1D agonist, has a higher oral bioavailability than any other triptan, with more than two thirds of the administered dose absorbed within the first hour both inside and outside of a migraine attack. Gender or the presence of food in the stomach does not affect its pharmacokinetic profile, and the compound has no clinically relevant interactions with other drugs. Among the available triptans, response rates at 2 hours range from 50% to 80%, with 20% to 50% of patients pain-free. Almotriptan 12.5 mg provides similar efficacy, with significant advantage over placebo at 30 minutes and a reliable consistency (75% in two of three attacks). Headache typically recurs in 25% to 45% of patients with most triptans. The recurrence rate with almotriptan 12.5 mg, 18% to 27%, is among the lowest reported. The tolerability of almotriptan 12.5 mg is close to that of placebo with a low incidence of central nervous system side effects and chest symptoms. In conclusion, almotriptan's consistent pharmacokinetics and good efficacy, in combination with excellent tolerability, make it an attractive choice in the acute treatment of migraine attacks.
Humans↗
Patient perceptions and treatment preferences in migraine management.
As the characteristics of migraine vary among patients and between attacks, multiple factors must be considered clinically to ensure that patients receive the most effective treatment strategy. Critical information required from the patient is general medical history, migraine-specific history, and the impact of migraine. Once the strategy of care and the optimal therapeutic plan are decided, the choice of therapeutic delivery must take into account patient preferences, compliance and clinical need. During the symposium, a case review and interview with a patient were conducted to illustrate the complex nature of integrating the assessment of signs, symptoms, disability, comorbidities and patient preferences. At the woman's first clinic visit, her Migraine Disability Assessment Scale (MIDAS) score was 70. Previous acute therapies had been only marginally effective, while previous prophylactic therapies had been discontinued because of adverse events or had also proved to be ineffective. The patient's current acute therapy was zolmitriptan 5mg, which she responds to well. Seven months after her first clinic visit, the patient's MIDAS score had decreased to 25. When asked about the relevance and utility of the MIDAS questionnaire, the patient felt that it asked about things that are important, helped her to understand the impact of migraine on her life, and accurately reflected her improvement. The patient also expressed an interest in trying more rapidly acting formulations of migraine-specific therapies in the future, such as a nasal spray formulation of zolmitriptan. The MIDAS questionnaire facilitates communication between physicians and patients to enable greater understanding of the impact of migraine. MIDAS grades can also be used in the stratification of treatment and for monitoring the course of illness and treatment outcomes. By increasing available treatment options, patient needs and preferences can be matched with specific features of migraine therapies. Taking patient preferences into account is likely to increase patient satisfaction and compliance, hopefully decreasing the degree of undertreatment of migraine that has been reported globally.
Female↗
Botulinum neurotoxin for the treatment of migraine and other primary headache disorders.
Botulinum toxin A (BoNT/A), a neurotoxin, is effective for treating a variety of disorders of involuntary muscle contraction, including cervical dystonia, blepharospasm and hemifacial spasm. It inhibits neurouscular signaling by blocking the release of acetylcholine at the neuromuscular junction. The biological effects of the toxin are transient with normal neuronal signaling returning within approximately 3-6 months post injection. Recently, clinical findings suggest that BoNT/A may inhibit pain associated with migraine and other headache types. The mechanism by which this toxin inhibits pain is under investigation, recent findings suggest that it inhibits the release of neurotransmitters from nociceptive nerve terminals and in this way may exert an analgesic effect. A number of retrospective open-label chart reviews and three placebo-controlled double-blind trials have demonstrated that localized injections of BTX-A significantly reduce migraine frequency, severity, and migraine-associated disability. The majority of patients in these studies experienced no BoNT/A mediated side effects; however, a small percentage of patients did report transient minor side effects including blepharoptosis, dipolpia, and injection-site weakness. Currently there are several large-scale randomized, placebo-controlled clinical trials in progress evaluating the efficacy, optimal dosing and side effect profile of this toxin as a novel treatment for migraine and other headache types. These studies may provide further evidence that BoNT/A is an effective option for the preventive treatment of migraine.
Botulinum Toxins, Type A↗