Treatment Strategies For Migraine Research Articles

Migraine Management in Medically Complex Patients: a Narrative Review.

The current review aims to provide an overview of migraine treatment strategies in medically complex patients, including those with renal, liver, and cardiovascular disease. In cardiovascular disease, gepants are likely safe for acute therapy; NSAIDs, ergotamines, and triptans are not recommended. Beta-blockers, ACEi/ARBs, and verapamil have potential cardiovascular benefits in addition to migraine preventive benefit. Frovatriptan requires no dose adjustments in kidney disease or in mild to moderate liver disease. Gepants are safe acute and preventive treatment options in mild and moderate renal and hepatic disease. TCAs and valproic acid require no dose adjustments in renal disease. OnabotulinumtoxinA is likely safe in cardiac, renal, and hepatic impairment. Although CGRP monoclonal antibodies are likely safe in renal and hepatic disease, further study is needed in these conditions as well as in cardiac disease, and no dosing recommendations are available. Effective options are available for those with complex medical comorbidities. Further research is required on the safety of newer migraine-specific therapies in these complex populations.

Reliability and Validity Study of the Migraine Interictal Burden Scale-4 in Turkish

ABSTRACT Objective: The objective of this study was to assess the reliability and validity of the Turkish version of the Migraine Interictal Burden Scale-4 (MIBS-4) in patients with migraine. MIBS-4 measures migraine-related interictal burden in four domains related to difficulty in planning at work or school, family and social life, and emotional/affective and cognitive stress. Materials and Methods: A total of 178 patients with migraine were enrolled in this multicenter, prospective study in two consecutive interviews with 4-week intervals. The comprehensibility, patient–physician reliability, internal consistency, test–retest reliability, and validity of the Turkish translation of MIBS-4 were analyzed. Results: In terms of comprehensibility of all MIBS-4 questions, a statistically significant agreement was obtained between the patient and the physician (intraclass correlation coefficient [ICC] = 0.713; P < 0.001, ICC = 0.851; P < 0.001, ICC = 0.637; and P < 0.001, ICC = 0.760; P < 0.001). No statistically significant difference was found between the comprehensibility of the first, second, third, and fourth questions of MIBS-4 according to the patient self-test and the physician interviews (P = 0.167, P = 0.068, P = 0.121, and P = 0.225, respectively). A significant high consistency was obtained between the first and second interview values (ICC = 0.891; P < 0.001). Cronbach’s alpha coefficient was obtained between 0.818 and 0.845, and the scale was obtained with high reliability. A statistically significant positive correlation was obtained between the first and second interview MIBS values and Headache Impact Test-6, and the correlation coefficients were obtained as 0.158 and 0.330, respectively (P = 0.036 and P < 0.001, respectively). Conclusion: These results demonstrated that the Turkish translation of MIBS-4 is equivalent to the English version in terms of internal consistency, and it has high test–retest reliability and validity. The Turkish version of MIBS-4 can serve as a reliable, useful, and valid tool for assessing the burden on patients between migraine attacks, as well as aiding health-care professionals in enhancing migraine treatment strategies in Türkiye.

Development of an innovative turn-on fluorescent probe for targeted in-vivo detection of nitric oxide in rat brain extracts as a biomarker for migraine disease

Nitric oxide (NO) is one of the reactive nitrogen species (RNS) that has been proposed to be a key signaling molecule in migraine. Migraine is a neurological disorder that is linked to irregular NO levels, which necessitates precise NO quantification for effective diagnosis and treatment. This work introduces a novel fluorescent probe, 2,3-diaminonaphthelene-1,4-dione (DAND), which was designed and synthesized to selectively detect NO in-vitro and in-vivo as a migraine biomarker. DAND boasts high aqueous solubility, biocompatibility, and facile synthesis, which enable highly selective and sensitive detection of NO under physiological conditions. NO reacts with diamine moieties (recognition sites) of DAND, results in the formation of a highly fluorescent product (DAND-NO) known as 1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione at λem 450 nm. The fluorescence turn-on sensing mechanism operates through an intramolecular charge transfer (ICT) mechanism. To maximize fluorescence signal intensity, parameters including DAND concentration, reaction temperature, reaction time and pH were systematically optimized for sensitive and precise NO determination. The enhanced detection capability (LOD = 0.08 μmol L−1) and high selectivity of the probe make it a promising tool for NO detection in brain tissue homogenates. This demonstrates the potential diagnostic value of the probe for individuals suffering from migraine. Furthermore, this study sheds light on the potential role of zolmitriptan (ZOLM), an antimigraine medication, in modulating NO levels in the brain of rats with nitroglycerin-induced migraine, emphasizing its significant impact on reducing NO levels. The obtained results could have significant implications for understanding how ZOLM affects NO levels and may aid in the development of more targeted and effective migraine treatment strategies.

Hypermobility spectrum disorders and active migraine in Israeli adolescents: A nationwide study.

To assess the association between hypermobility spectrum disorders/hypermobile type Ehlers Danlos Syndrome (HSD/hEDS) and migraine in a national sample of adolescents in Israel. The association between HSD/hEDS and migraine is unclear, even more so in pediatric populations. This population-based, cross-sectional study included 1,627,345 Israeli adolescents (945,519/1,626,407 [58%] males; mean age 17 ± 0.5 years) who were medically assessed before mandatory military service during 1998-2020. Diagnoses of migraine with at least one attack per month (active migraine) and HSD/hEDS were confirmed by certified specialists. The prevalences of active migraine in adolescents with and without HSD/hEDS were computed and the association between HSD/hEDS and active migraine was examined. Active migraine was significantly more prevalent in adolescents with HSD/hEDS (307/4686 [6.5%]) compared to those without HSD/hEDS (51,931/1,621,721 [3.2%]) (OR = 2.16, 95% CI 1.90-2.45). The association between HSD/hEDS and active migraine persisted in a multivariable analysis (OR = 2.08, 95% CI 1.85-2.34) and in several sensitivity analyses. We found a significant association between HSD/hEDS and active migraine in both male and female adolescents. Clinical awareness of the association can promote early diagnosis and treatment of migraine. Further research is required to identify appropriate pharmacologic and nonpharmacologic migraine treatment strategies for individuals with HSD/hEDS.

De novo protein synthesis is necessary for priming in preclinical models of migraine.

Migraine attacks are often triggered by normally innocuous stimuli, suggesting that sensitization within the nervous system is present. One mechanism that may contribute to neuronal sensitization in this context is translation regulation of new protein synthesis. The goal of this study was to determine whether protein synthesis contributes to behavioral responses and priming in preclinical models of migraine. Mice received a dural injection of interleukin-6 in the absence or presence of the protein synthesis inhibitor anisomycin or the translation initiation inhibitor 4EGI-1 and were tested for facial hypersensitivity. Upon returning to baseline, mice were given a second, non-noxious dural injection of pH 7.0 to test for priming. Additionally, eIF4ES209Amice lacking phosphorylation of mRNA cap-binding protein eIF4E received dural interleukin-6 or were subjected to repeated restraint stress and then tested for facial hypersensitivity. After returning to baseline, mice were given either dural pH 7.0 or a systemic sub-threshold dose of the nitric oxide donor sodium nitroprusside and tested for priming. Dural injection of interleukin-6 in the presence of anisomycin or 4EGI-1 or in eIF4ES209Amice resulted in the partial attenuation of acute facial hypersensitivity and complete block of hyperalgesic priming. Additionally, hyperalgesic priming following repeated restraint stress was blocked in eIF4ES209Amice. These studies show that de novo protein synthesis regulated by activity-dependent translation is critical to the development of priming in two preclinical models of migraine. This suggests that targeting the regulation of protein synthesis may be a novel approach for new migraine treatment strategies.

Prevention of migraine during prodromal phase caused by weather changes

Although migraine has been reported to have different inducing factors, changes in weather parameters such as atmospheric pressure, rain, humidity, temperature, wind, and lightning are well known important environmental factors. In recent years, reports of abnormal weather conditions such as heat waves in summer, heavy snow in winter, localized heavy rain, and abnormally light rain, as well as tropical cyclones are increasing. In today’s extreme weather conditions, the worsening, diver­sification, and chronicity of migraine symptoms is concerning, and a higher level of treatment for migraine is required than ever before. Drug therapy is used as the principal treatment for migraine. If the acute treatment alone interferes with daily life, the principle is to combine daily preventive therapies to reduce the frequency, severity, and duration of the migraine attacks. However, there are several cases wherein migraine is poorly controlled only with their combination. Several patients with migraine experience prodromal symptoms, including stiff neck and shoulder as well as sensitivity to light and sound, before migraine attacks. In recent years, it has been reported that sensors for detecting atmospheric pressure exist in the vestibular part of the inner ear, and it has been shown that changes in atmospheric pressure may activate the vestibular nerve activity. We reported that difenidol, a vestibular nerve modulator, was administered to prevent or alleviate migraine attacks during the prodromal phase caused by change in weather. Prevention during the prodromal phase and prevention based on weather prediction are new treatment strategies for migraine. In today’s extreme weather conditions, 3–P therapy that combines the three treatment strategies of prevention, prodrome, and prediction is useful.

A Cross-Sectional Analysis of Migraine-Related Disability in CADASIL: A Mayo Clinic Cohort.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is inherited microangiopathy characterized by recurrent subcortical infarcts. A majority of those with CADASIL report coexistent migraine with aura. The authors aim to quantitatively describe migraine-related disability within a CADASIL cohort. A cross-sectional analysis was performed in a cohort of CADASIL. The Migraine Disability Assessment (MIDAS) quantified migraine-related disability. Further metrics obtained include first and last migraine, aura semiology, and therapeutic measures. Twenty-four individuals were included [63% (15/24) female individuals; mean age, 56 y; range, 34 to 81 y]. Fifty-four percent (13/24) reported migraine, whereas 46% (11/24) reporting varying degrees of migraine-related disability. MIDAS Questionnaire scores appeared bimodal: 58% (14/24) scored 0 to 5, 7% (1/24) scored 6 to 10, 7% (1/24) scored 11 to 20 and 33% (8/24) scored over 20. Severe disability was associated with the multiplicity of aura semiologies and poor response to pharmacologic prophylaxis. A bimodal distribution of migraine-related disability was observed. A third of individuals had a severe disability and appeared medically refractory to medical migraine prophylactic measures. This study may serve as a reference point for future trials quantitatively gauging response of novel migraine treatment strategies within this unique population.

Understanding migraine and psychiatric comorbidity.

This article describes recent trends in our understanding of the role of psychiatric disorders in the experience and treatment of migraine, and the role of migraine in the experience and treatment of psychiatric disorders. Although the majority of studies evaluating psychiatric comorbidity in migraine have focused on depression, anxiety, and bipolar disorders are highly associated with migraine and relevant for prognosis and treatment planning. Comorbid psychiatric disorders may be associated with poorer treatment response for some acute pharmacotherapies; however, people with comorbid migraine and mood or anxiety disorders can achieve large responses to preventive pharmacologic and behavioral therapies. Emerging research is developing and evaluating behavioral treatments designed to manage cooccurring migraine and mood or anxiety disorders. Stigma related to psychiatric disorders has been well characterized, and could exacerbate extant migraine-related stigma. Anxiety and mood disorders are prevalent in people with migraine, although not ubiquitous. Psychiatric comorbidity is associated with greater migraine symptoms and disability; however, people with comorbid depression or anxiety are amenable to preventive migraine treatment. Research regarding migraine treatment strategies optimized for people with comorbid psychiatric disorders is critical to advancing care and reducing stigma for this important subpopulation of people with migraine.

Behavioral treatments for migraine management: useful at each step of migraine care.

Migraine is a disabling and prevalent disorder. Migraine is most effectively treated with a stepped care approach, where patients initially receive a broad level of care (primary care) and proceed to receive increasingly specialized care throughout the course of treatment. Behavioral treatments for migraine modify behaviors of people with migraine with the intention to prevent migraine episodes and secondary consequence of migraine. Behavioral treatments can be incorporated into each level of the stepped care approach for migraine treatment. In this article, we provide a rationale for including behavioral treatment strategies in the treatment of migraine. We then describe and review the evidence for behavioral treatment strategies for migraine, including patient education, relaxation strategies, biofeedback, and cognitive behavioral treatment strategies. Finally, we describe how behavioral treatments can be integrated into a stepped care approach for migraine care.

Pharmacological Acute Migraine Treatment Strategies: Choosing the Right Drug for a Specific Patient

Background:In our targeted review (Section 2), 12 acute medications received a strong recommendation for use in acute migraine therapy while four received a weak recommendation for use. Strong recommendations were made to avoid use of two other medications, except for exceptional circumstances. Two anti-emetics received strong recommendations for use as needed.Objective:To organize the available acute migraine medications into acute migraine treatment strategies in order to assist the practitioner in choosing a specific medication(s) for an individual patient.Methods:Acute migraine treatment strategies were developed based on the targeted literature review used for the development of this guideline (Section 2), and a general literature review. Expert consensus groups were used to refine and validate these strategies.Results:Based on evidence for drug efficacy, drug side effects, migraine severity, and coexistent medical disorders, our analysis resulted in the formulation of eight general acute migraine treatment strategies. These could be grouped into four categories: 1) two mild-moderate attack strategies, 2) two moderate-severe attack or NSAID failure strategies, 3) three refractory migraine strategies, and 4) a vasoconstrictor unresponsive-contraindicated strategy. In addition, strategies were developed for menstrual migraine, migraine during pregnancy, and migraine during lactation. The eight general treatment strategies were coordinated with a “combined acute medication approach” to therapy which used features of both the “stratified” and the “step care across attacks” approaches to acute migraine management.Conclusions:The available medications for acute migraine treatment can be organized into a series of strategies based on patient clinical features. These strategies may help practitioners make appropriate acute medication choices for patients with migraine.

Canadian Headache Society Guideline: Acute Drug Therapy for Migraine Headache

The primary objective of this guideline is to assist the practitioner in choosing an appropriate acute medication for an individual with migraine, based on current evidence in the medical literature and expert consensus. It is focused on patients with episodic migraine ( headache on ≤ 14 days a month). A detailed search strategy was used to find a relevant meta-analyses, systematic reviews and randomized double-blind controlled trials. Recommendations were graded with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, using a consensus group. In addition, a general literature review and expert consensus were used for aspects of acute therapy for which randomized controlled trials were not available. Twelve acute medications received a strong recommendation for use in acute migraine therapy (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zomitriptan, ASA, ibuprofen, naproxen sodium, diclofenac potassium, and acetaminophen). Four received a weak recommendation for use (dihydroergotamine, ergotamine, codeine-containing combination analgesics, and tramadol- containing medications). Three of these were NOT recommended for routine use (ergotamine and codeine- and tramadol- containing medications). Strong recommendations were made to avoid use of butorphanol and butalbital- containing medications. Metoclopramide and domperidone were strongly recommended for use when necessary. Our analysis also resulted in the formulation of eight general acute migraine management strategies. These were grouped into: 1) two mild-moderate attack strategies, 2) two moderate-severe attack or NSAID failure strategies, 3) three refractory migraine strategies, and 4) a vasoconstrictor unresponsive-contraindicated strategy. Additional were developed for menstrual migraine during pregnancy, and migraine during lactation. This guideline provides evidence-based advice on acute pharmacological migraine therapy, and should be helpful to both health professionals and patients, The available medications have been organized into a series of strategies based on patient clinical features. These strategies may help practitioners make appropriate acute medication choices for patients with migraine.

Pharmacological Acute Migraine Treatment Strategies: Choosing the Right Drug for a Specific Patient

ABSTRACT:Background:In our targeted review (Section 2), 12 acute medications received a strong recommendation for use in acute migraine therapy while four received a weak recommendation for use. Strong recommendations were made to avoid use of two other medications, except for exceptional circumstances. Two anti-emetics received strong recommendations for use as needed.Objective:To organize the available acute migraine medications into acute migraine treatment strategies in order to assist the practitioner in choosing a specific medication(s) for an individual patient.Methods:Acute migraine treatment strategies were developed based on the targeted literature review used for the development of this guideline (Section 2), and a general literature review. Expert consensus groups were used to refine and validate these strategies.Results:Based on evidence for drug efficacy, drug side effects, migraine severity, and coexistent medical disorders, our analysis resulted in the formulation of eight general acute migraine treatment strategies. These could be grouped into four categories: 1) two mild-moderate attack strategies, 2) two moderate-severe attack or NSAID failure strategies, 3) three refractory migraine strategies, and 4) a vasoconstrictor unresponsive-contraindicated strategy. In addition, strategies were developed for menstrual migraine, migraine during pregnancy, and migraine during lactation. The eight general treatment strategies were coordinated with a “combined acute medication approach” to therapy which used features of both the “stratified” and the “step care across attacks” approaches to acute migraine management.Conclusions:The available medications for acute migraine treatment can be organized into a series of strategies based on patient clinical features. These strategies may help practitioners make appropriate acute medication choices for patients with migraine.

Migraine predicts physical and pain symptoms among psychiatric outpatients

BackgroundNo study has been performed to compare the impacts of migraine and major depressive episode (MDE) on depression, anxiety and somatic symptoms, and health-related quality of life (HRQoL) among psychiatric outpatients. The aim of this study was to investigate the above issue.MethodsThis study enrolled consecutive psychiatric outpatients with mood and/or anxiety disorders who undertook a first visit to a medical center. Migraine was diagnosed according to the International Classification of Headache Disorders, 2nd edition. Three psychometric scales and the Short-Form 36 were administered. General linear models were used to estimate the difference in scores contributed by either migraine or MDE. Multiple linear regressions were employed to compare the variance of these scores explained by migraine or MDE.ResultsAmong 214 enrolled participants, 35.0% had migraine. Bipolar II disorder patients (70.0%) had the highest percentage of migraine, followed by major depressive disorder (49.1%) and only anxiety disorder (24.5%). Patients with migraine had worse depression, anxiety, and somatic symptoms and lower SF-36 scores than those without. The estimated differences in the scores of physical functioning, bodily pain, and somatic symptoms contributed by migraine were not lower than those contributed by MDE. The regression model demonstrated the variance explained by migraine was significantly greater than that explained by MDE in physical and pain symptoms.ConclusionsMigraine was common and the impact of migraine on physical and pain symptoms was greater than MDE among psychiatric outpatients. Integration of treatment strategies for migraine into psychiatric treatment plans should be considered.

Can migraine prophylaxis prevent acute mountain sickness at high altitude?

Acute mountain sickness (AMS) develops in people trekking at high altitude. The underlying mechanism is vasodilation due to low pressure of oxygen. However, individual susceptibility for AMS is unknown, thus, one cannot predict when or to whom it happens. Because AMS usually begins with headache, and because migraineurs are more vulnerable to AMS, we studied by the literatures review on the mechanism and clinical features in common, and assessed the treatment modalities for both disorders. This led to us the following hypothesis that, migraine prophylaxis may prevent or delay the onset of AMS at high altitude. Clinical features of AMS include nausea or vomiting when it progresses. Hypobaric hypoxia, dehydration or increased physical exertion trigger or aggravate both disorders. In migraine, cerebral vasodilation can happen following alteration of neuronal activity, whereas the AMS is associated with peripheral vessel dilation. Medications that dilate the vessels worsen both conditions. Acute treatment strategies for migraine overlap with to those of AMS, including drugs such as vasoconstrictors, or other analgesics. To prevent AMS, adaptation to high altitude or pharmacological prophylaxis, i.e., acetazolamide has been recommended. This carbonic anhydrase inhibitor lowers serum potassium level, and thus stabilizes membrane excitability. Acetazolamide is also effective on specific forms of migraine. Taken together, these evidences implicate that migraine prophylaxis may prevent or delay the onset of AMS by elevating the threshold for high altitude.

Early Treatment in Migraine: How Strong is the Current Evidence?

Over the last 10 years, triptans (serotonin 5-HT(1B/1D) receptor agonists) have proved to be efficacious in treating migraine pain. However, recent evidence suggests that patients are still not receiving optimal pain management, particularly in clinical trials, where triptan treatment is generally not initiated until pain has reached moderate intensity. Pathophysiological evidence indicates that if treatment is initiated at an early stage, while pain is still mild and before the onset of central sensitization, outcomes for patients may be improved. In addition, a small number of clinical trials have been reported in which triptans were taken early (within 1 h of pain onset) or while pain was still mild; although constraints of trial design and data analysis limit definite conclusions, overall the results suggest that this early/mild approach results in more rapid and sustained pain relief. New studies are therefore needed to clarify the clinical benefits of early treatment, whilst taking into account potential risks, such as medication overuse. Ultimately, migraine treatment strategies require optimization in order to meet patient expectations and to reduce the current burden of migraine-associated disability.

New Migraine and Pain Research

An understanding of the pathophysiology and pharmacology of migraine has been driven by astute clinical observations, elegant experimental medicine studies and importantly by the introduction of highly effective selective anti-migraine agents such as the Triptan 5-HT(1B/1D) agonists. New investigational migraine therapies such CGRP antagonists target key components of the trigeminal sensory neuroinflammatory response and show promise for the future. Cutting edge molecular profiling studies looking at gene expression during chronic pain are now being used to reveal the cell biology of pain and new potential therapeutic targets. Translational neuroimaging research can link the laboratory and the clinic and is now being used to help understand the neural systems biology of migraine. Research into migraine has generated sophisticated hypotheses that encompass primary CNS dysfunction, trigeminovascular activation, pain perception and activation of associated neural circuits involved in affective functions providing a rich framework within which to design and test future migraine treatment strategies.

Strategies to Improve Migraine Treatment Results

The purpose of this review is to describe strategies for optimizing the use of available agents for acute migraine therapy. Patient satisfaction with migraine therapy depends on obtaining rapid and complete resolution of pain and preventing headache recurrence, making 2-h pain free and sustained pain free more relevant endpoints than 2-h pain relief for assessing acute migraine therapies. Many treatment guidelines recommend a step-care approach to migraine management, that is, starting with a simple analgesic, followed by various combination analgesics, allowing a migraine-specific drug (e.g. a triptan) only after the patient has demonstrated an inadequate response to non-specific treatments. This can result in prolonged morbidity and patients lapsing from care. In the stratified-care approach, the initial treatment is selected according to the individual patient’s migraine severity and associated disability, promoting the use of migraine-specific treatments as first-line agents for patients with disabling migraines. Another strategy, triptan treatment during mild headache pain, has been shown to improve treatment success rates compared with treatment delayed until pain is moderate to severe. Treatment before the development of central sensitization is thought to underlie the improvement in outcomes. In conclusion, migraine treatment strategies such as the stratified-care approach and the administration of medication while pain is mild will help increase treatment success rates and substantially reduce patient suffering and disability.

Cost‐Effectiveness of Topiramate in Migraine Prevention: Results From a Pharmacoeconomic Model of Topiramate Treatment

Patients whose migraines are frequent, cause disruptions of daily routines, or are unresponsive to acute treatment are primary candidates for preventive migraine therapy. This cost-effectiveness model assesses the clinical and economic impact of topiramate (TPM) therapy versus no preventive treatment for migraine headache in the United States. Despite significant progress in treatment options, the economic burden of migraine to patients, employers, health systems, and society is substantial. Treatment strategies for migraine are directed toward managing acute episodes. However, preventive therapy should be used for patients with frequent migraine attacks (>2 per month) or those experiencing attacks that disrupt daily routines. Data for the model were obtained from the published literature and pooled results of two randomized, double-blinded, placebo-controlled trials of TPM in migraine prevention. Model inputs included baseline migraine frequency (the base case assumed 6 per month, consistent with the average rate in the TPM trials), treatment discontinuation (including discontinuation due to adverse events), treatment response (ie, > or = 75%, 50% to 75%, and <50% reduction in migraine frequency), cost of preventive therapy (TPM plus physician visits for medication titration), cost of acute treatment per attack (including pharmacy and medical service costs), hours of disability per attack, hourly wage, and quality-of-life (utility) weights. Model outcomes included the number of migraines averted, disability hours, total cost of acute and preventive treatment, and lost wages. Results were expressed as cost per migraine averted and cost per quality-adjusted life years (QALY). All costs were stated as 2002 U.S. dollars. We also conducted sensitivity analyses to assess the robustness of model findings with respect to variation in key parameters. We estimated that the use of TPM would prevent 1.85 migraines per patient and almost 5 hours of disability per month versus no preventive treatment. Resulting savings in cost of acute treatment (dollar 27) and work loss (dollar 51) offset 68% of the expected monthly cost of TPM (dollar 113). The incremental cost per migraine averted was dollar 19, while the incremental cost per QALY was estimated to be dollar 10,888 (dollar 26,191 when indirect costs were excluded from the analysis). Model results were sensitive to baseline migraine rate and gain in health utility from migraine prevention. Economic savings associated with reduced migraine frequency offset approximately two thirds of the cost of preventive TPM therapy. The cost-effectiveness of TPM depends on utility gains associated with a reduced frequency of migraine headaches, which is the subject of ongoing research. However, results from our model suggest that the use of TPM in prevention of migraine may offer reasonable value for money relative to many well-accepted medical interventions.

Management of primary headache: serendipity and science.

Most patients find some relief with current agents, even though a poor understanding of the causes of chronic primary headache limits prophylaxis and treatment. The author reviews current preventive and treatment strategies for migraine, chronic tension headache, cluster headache, and substance withdrawal headache.

Pathophysiology and pharmacology of migraine. Is there a place for antiemetics in future treatment strategies?

This article reviews the pathophysiology and pharmacology of emesis in relation to migraine pathogenesis. Also, the place of antiemetic and gastrointestinal prokinetic agents in current and future acute migraine treatment strategies is reviewed. The mechanisms of action of current and novel acute migraine therapies are considered with respect to the neurogenic and vascular hypothesis. Control of migraine-associated nausea and vomiting is often achieved with the benzamide dopamine D2 receptor antagonist metoclopramide. This drug also has 5HT3 receptor antagonist activity and reproducibly stimulates gastric motility to increase the availability of orally administered drugs. Other antiemetic and gastroprokinetic agents with potential value for the treatment of migraine-associated nausea and vomiting could speed absorption of oral antimigraine therapies without central nervous system side effects. Domperidone, a dopamine D2 receptor antagonist that does not cross the blood brain barrier is relatively free of the central side-effect liability of metoclopramide. Cisapride, a benzamide 5HT4 receptor agonist gastrointestinal prokinetic drug, lacks dopamine antagonist activity. A controlled comparison of these agents as migraine co-therapies could provide information on the importance of peripheral and central mechanisms in migraine-associated nausea and vomiting and improve antimigraine treatment options.