Paul Rizzoli

The 2012 AHS/AAN Guidelines for Prevention of Episodic Migraine: A Summary and Comparison With Other Recent Clinical Practice Guidelines

Background.— Updated guidelines for the preventive treatment of episodic migraine have been issued by the American Headache Society (AHS) and the American Academy of Neurology (AAN). We summarize key 2012 guideline recommendations and changes from previous guidelines. We review the characteristics, methods, consistency, and quality of the AHS/AAN guidelines in comparison with recently issued guidelines from other specialty societies.

Tension-Type Headache

#### Summary points Tension-type headache is a neurological disorder characterised by a predisposition to attacks of mild to moderate headache with few associated symptoms. The diagnosis is based on the history and examination. Over the past few decades research on headache has centred on migraine, and much of the best quality evidence for the treatment of tension-type headache is decades old. Some consensus based treatment guidelines are available (see Additional Educational Resources box towards the end of this article). Treatment has changed little over the past two decades. Many patients self treat acute attacks and seek advice when attacks become frequent or chronic. This review focuses on how to identify and manage patients who require medical advice about acute attacks and preventive treatment to minimise further attacks. Box 1 summarises the criteria for tension-type headache outlined in the second revision of the international classification of headache disorders, in which such headache is classified according to whether it is episodic or chronic and whether muscle tenderness is present.1 #### Box 1 Diagnostic criteria for tension-type headache*

Hormonal Management of Migraine Associated With Menses and the Menopause: A Clinical Review

Objective.—This article reviews hormonal strategies used to treat headaches attributed to the menstrual cycle or to peri‐ or postmenopausal estrogen fluctuations. These may occur as a result of natural ovarian cycles, or in response to the withdrawal of exogenously administered estrogen.

Acute and Preventive Treatment of Migraine

Purpose of Review: Migraine remains underdiagnosed and undertreated despite advances in the understanding of its pathophysiology and management. This article focuses on acute and preventive treatment of migraine, including the mechanisms of action, dosing and side effects of medications, and strategies for the most effective care.Recent Findings: Best practice suggests that acute migraine treatment should be stratified based on the severity of the individual event, with a goal of returning the patient to full function within 2 hours of treatment. Migraine prevention strategies continue to be underused in the United States. More than 1 in 4 patients with migraines may be candidates for preventive therapy. To obtain the best results from preventive therapy, slow titration to an adequate dose for an adequate timeframe with good documentation of the results is recommended.Summary: This article reviews several options for managing acute attacks, including information on expected efficacy, dosing, and adverse effects. Strategies for effective application of acute therapies are discussed. Prevention can be added to acute therapy depending on headache characteristics such as frequency, severity, disability, and the presence of comorbid conditions. The mechanisms of action of preventive medications and strategies for their most effective use are discussed.

Preventive Pharmacotherapy in Migraine

Migraine prevention can be instrumental in the effective management of the migraine patient but remains underused in treatment of this common, chronic, and often debilitating condition. The development of methysergide as the first migraine preventive agent not only laid the groundwork for our current thinking about migraine prevention, but also created a paradigm shift away from migraine as a psychological issue and toward migraine as a legitimate medical condition.

Biomarkers in Migraine: Their Promise, Problems, and Practical Applications

Biomarkers are physical signs or laboratory measurements that “occur in association with a pathological process and have putative diagnostic and/or prognostic utility.” Biomarkers hold considerable promise for understanding and intervening in the disease process of migraine. They may permit recognition of individuals at risk of developing migraine, improve the timing, accuracy, and precision of migraine diagnosis, and serve as indicators of treatment response and disease progression. Furthermore, they hold great promise for research. At the same time, there are important limitations to the use of biomarkers in migraine, including problems with validity, reliability, accuracy, and precision. Legal, ethical, and cost considerations are also important. This review describes the potential uses and limitations of biomarkers in migraine diagnosis, treatment, and research.

Beta-blockers for migraine.

Sometimes the observations by one astute clinician of one patient lead to new treatments. In 1966, Rabin et al in a study of propranolol to prevent angina, noted that a 59-year-old man reported that his migraines and angina improved on propranolol but the migraines returned after a crossover to placebo medication. Since then, propranolol has become a first-line agent for migraine prevention with increasing caveats, some real, others questionable.

Medication overuse headache: An entrenched idea in need of scrutiny

It is a widely accepted idea that medications taken to relieve acute headache pain can paradoxically worsen headache if used too often. This type of secondary headache is referred to as medication overuse headache (MOH); previously used terms include rebound headache and drug-induced headache. In the absence of consensus about the duration of use, amount, and type of medication needed to cause MOH, the default position is conservative. A common recommendation is to limit treatment to no more than 10 or 15 days per month (depending on medication type) to prevent headache frequency progression. Medication withdrawal is often recommended as a first step in treatment of patients with very frequent headaches. Existing evidence, however, does not provide a strong basis for such causal claims about the relationship between medication use and frequent headache. Observational studies linking treatment patterns with headache frequency are by their nature confounded by indication. Medication withdrawal studies have mostly been uncontrolled and often have high dropout rates. Evaluation of this evidence suggests that only a minority of patients required to limit the use of symptomatic medication may benefit from treatment limitation. Similarly, only a minority of patients deemed to be overusing medications may benefit from withdrawal. These findings raise serious questions about the value of withholding or withdrawing symptom-relieving medications from people with frequent headaches solely to prevent or treat MOH. The benefits of doing so are smaller, and the harms larger, than currently recognized. The concept of MOH should be viewed with more skepticism. Until the evidence is better, we should avoid dogmatism about the use of symptomatic medication. Frequent use of symptom-relieving headache medications should be viewed more neutrally, as an indicator of poorly controlled headaches, and not invariably a cause.

Tolerance and loss of beneficial effect during migraine prophylaxis: clinical considerations.

A familiar situation in migraine treatment is the patient with an initial positive response to prophylactic drug therapy who later experiences relapse. The goals of this paper are to provide a theoretical framework to help doctors think about this problem, to evaluate factors and response patterns that may be associated with different causes of relapse, and to suggest clinical strategies that may aid in its management. Six key explanations for loss of benefit from prophylactic therapy are: (1) pharmacokinetic, pharmacodynamic, and behavioral drug tolerance; (2) non‐specific or placebo effects; (3) natural variability in disease activity; (4) disease progression; (5) inaccurate recall of treatment effects; and (6) drug delivery problems. Current options for patients who experience loss of benefit from prophylactic therapy include traditional techniques such as switching, re‐trying, rotating, or combining drugs. Selected behavioral and environmental treatment techniques might also be useful. We describe a practical, structured approach to evaluation and management of relapse with migraine prophylaxis.

Tolerance to the beneficial effects of prophylactic migraine drugs: a systematic review of causes and mechanisms.

Loss of benefit of a previously effective treatment regimen, also known as tolerance, can be an important barrier to the successful preventive treatment of migraine. We undertook a systematic review of the literature to identify the prevalence and possible mechanisms of drug tolerance in migraine prophylaxis. Results demonstrate that the frequency of tolerance to prophylactic migraine treatment is unknown, but available data support an estimate that it occurs in 1‐8% of patients receiving prophylaxis. Four broad types of tolerance were identified that are likely to be relevant to migraine prophylaxis. These are pharmacokinetic, pharmacodynamic, behavioral, and cross tolerance. The mechanisms that underlie these types of tolerance determine whether their effects can be overcome or minimized. For example, certain forms of tolerance may be affected by manipulation of environmental cues associated with drug administration, by the order in which drugs are used, and by the concomitant use of other medications. Many medications used for migraine prophylaxis exert their effects through the endogenous opioid system. The implications of this finding are explored, particularly the parallels between medication overuse headache and tolerance to migraine prophylaxis. Given the many ways in which tolerance to migraine medications may develop, in some ways it is not surprising that migraine‐preventive drugs stop working; it is more surprising that in many cases they do not.