The American Headache Society Position Statement on Integrating New Migraine Treatments Into Clinical Practice

American Headache Society



In This Article

Preventive Treatment

The goals of migraine prevention are to:[21–23]

  • Reduce attack frequency, severity, duration, and disability

  • Improve responsiveness to and avoid escalation in use of acute treatment

  • Improve function and reduce disability

  • Reduce reliance on poorly tolerated, ineffective, or unwanted acute treatments

  • Reduce overall cost associated with migraine treatment

  • Enable patients to manage their own disease to enhance a sense of personal control

  • Improve health-related quality of life (HRQoL)

  • Reduce headache-related distress and psychological symptoms

Preventive treatments are an important part of the overall approach for a proportion of people with migraine, and multiple evidence-based guidelines are available.[19,22,24–27] None of the currently available oral preventive treatments were designed specifically for migraine, and many oral preventive treatments have limited to moderate efficacy, moderate to high rates of adverse events (AEs), contraindications, or interactions that limit use. These factors explain in part why few patients with migraine use preventive treatment (3–13%), even though it is believed that nearly 40% of those with episodic migraine, and almost all of those with chronic migraine, in the general population would benefit.[8,28]

Indications for Preventive Treatment

The recommendations for when to initiate preventive treatment are unchanged. Patients with migraine should be considered for preventive treatment in any of the following situations:[21–23]

  • Attacks significantly interfere with patients' daily routines despite acute treatment

  • Frequent attacks (≥4 MHDs)

  • Contraindication to, failure, or overuse of acute treatments, with overuse defined as:

    • 10 or more days per month for ergot derivatives, triptans, opioids, combination analgesics, and a combination of drugs from different classes that are not individually overused

    • 15 or more days per month for nonopioid analgesics, acetaminophen, and nonsteroidal antiinflammatory drugs (NSAIDs [including aspirin])

  • AEs with acute treatments

  • Patient preference

Prevention should also be considered in the management of certain uncommon migraine subtypes, including hemiplegic migraine, migraine with brainstem aura, migraine with prolonged aura, and those who have previously experienced a migrainous infarction, even if there is low attack frequency.[21–23]

Patient Identification

Patients are most often selected for preventive treatment based on attack frequency and degree of disability. Consensus guidelines identify groups of patients where preventive treatment should be either "offered" or "considered" based on these parameters (Table 2).[8] Another element of identification involves reviewing the history of medication use for acute treatment and treatment response. Those with migraine with poorly controlled attacks are at risk of acute medication overuse, medication overuse headache (Table 3) and progression to chronic migraine, and it is possible that overuse of medications for the acute treatment of headache may reduce the effectiveness of some preventive treatments.[22,30] Before a preventive treatment plan is developed, measures to ensure appropriate use (eg, drug type, route and timing of administration, frequency) of acute treatments coupled with education and lifestyle modifications should be initiated.[1]

Developing Treatment Plans for Traditional Oral Preventive Therapies

Preventive treatment selection is based on evidence of efficacy, provider experience, tolerability, patient preference, headache subtype, and comorbidities, taking into account women of childbearing potential, especially those who are currently pregnant, breastfeeding or attempting to conceive. There are several basic principles to guide the initiation, titration, and, if necessary, cessation of preventive treatment.[21,23,31]

Use evidence-based preventive treatments. The use of evidence-based treatments (Table 4) is important to the success of migraine prevention. Based on the level of evidence for efficacy and the American Academy of Neurology (AAN) scheme for classification of evidence, the following oral treatments have established efficacy and should be offered for migraine prevention: antiepileptic drugs (divalproex sodium, valproate sodium, topiramate); beta-blockers (metoprolol, propranolol, timolol); and frovatriptan (for short-term preventive treatment of menstrual migraine). An important exception to the use of valproate sodium and topiramate is that, due to risk of birth defects, it must not be prescribed to women of childbearing potential who are not using a reliable method of birth control.[34,35] The following treatments available by prescription are probably effective and should be considered for migraine prevention: antidepressants (amitriptyline, venlafaxine); beta-blockers (atenolol, nadolol); and angiotensin receptor blockers (candesartan).[19,33] Although evidence can narrow the range of therapeutic options, it does not replace clinical judgment. Preventive treatment plans must be designed to meet the needs of individual patients, and they may involve combining older and newer treatments as well as complex or nontraditional approaches.[19] In addition, evidence-based medicine is dynamic, and current practices may reflect the incorporation of more recent clinical trial results before they reach the creation or revision of existing treatment guidelines.

Start low and titrate.  Start oral treatments at a low dose and titrate slowly until the target response develops, the maximum or target dose is reached, or tolerability issues emerge.[21,23] When there is a partial but suboptimal response or dose-limiting AEs, combining preventive drugs from different drug classes may be useful.

Reach a therapeutic dose. With oral treatments, set an initial target dose (eg, 100 or 200 mg topiramate) and advise patients to stop the titration if the maximal dose is reached, when efficacy is optimal, or when AEs become intolerable.

Give an adequate trial. Give oral preventive treatments an adequate trial of at least 8 weeks at a target or usual effective dose to optimize the possibility of a therapeutic response. Before lack of effectiveness can be determined in patients with chronic migraine, prevention plans should be followed for a minimum of 8 weeks at a target therapeutic dose for oral treatments. If there is no response to treatment after 8 weeks at a target or usual effective dose switching preventive treatments is recommended. Patients with a partial response should be counseled that cumulative benefits may occur over 6 to 12 months of continued use.

Establish realistic expectations. When patients are introduced to migraine prevention, they may expect that attacks will cease soon after starting treatment but most established therapies have treatment latencies. The patient should be involved in the process to help establish individual treatment expectations. Thus, it is crucial that patients understand that any of the following can define success in migraine prevention:

  • 50% reduction in the frequency of days with headache or migraine

  • Significant decrease in attack duration as defined by patient

  • Significant decrease in attack severity as defined by patient

  • Improved response to acute treatment

  • Reduction in migraine-related disability and improvements in functioning in important areas of life

  • Improvements in health related quality of life and reduction in psychological distress due to migraine

In some patients, a less than 50% reduction in monthly headache days (MHDs) produces benefits while in others, especially those with daily or continuous headache, a significant reduction in the overall severity of headache may lead to improvements in function and HRQoL and a reduction in headache-related disability.[36] Patients should also understand the most common AEs and their typical frequency and severity, as well as the potential for rare but serious AEs. The success of preventive therapy depends on establishing realistic patient expectations for the given treatment(s).[23]

Optimize drug selection. The selection of preventive treatment should be based on evidence for efficacy; provider experience; tolerability; patient preference; headache subtype; comorbid and coexistent illnesses; concomitant medications; physiological factors (eg, heart rate, blood pressure); body habitus; and pregnancy or the potential for pregnancy among women. Comorbid and coexistent conditions are very important; drug selection may involve choosing treatments known to have efficacy for a comorbid condition or by avoiding drugs that may exacerbate comorbid or coexisting illness or interact with coadministered medications. A single drug for multiple conditions should be avoided if there is a risk of undertreatment of any single condition,[37] as optimal treatment may require the use of a separate class of medication.[23] Try to avoid preventive treatments (especially valproate sodium and topiramate[34,35]) in pregnant or lactating women and those who are trying to conceive, and discuss the potential for AEs on a pregnancy and a developing fetus in women of childbearing age. Since migraine may improve or remit over time, it is important to reevaluate therapeutic response and, if possible, taper or discontinue treatment if patients no longer meet the criteria for offering preventive treatment. However, caution must be exercised in patients who have established, longstanding chronic migraine or in those who have failed multiple prior attempts with preventive treatments. Once control is established, like the control of any chronic disease, the decision to discontinue or taper treatment should be a shared decision between patient and clinician, as it is possible that premature discontinuation can lead to exacerbation and control may not be easily recaptured even after restarting a treatment that was once effective.

Maximize adherence. The long-term adherence to oral preventive treatment is poor, mainly due to suboptimal efficacy and poor tolerability.[28] A study of adherence to 14 oral migraine preventive medications used to treat patients with chronic migraine (N = 8688) found adherence rates between 26 to 29% at 6 months and 17 to 20% at 12 months.[38] Patient education about dose adjustments, treatment expectations, and AEs may improve adherence. Patient preference is important in treatment decisions and shared decision making leads to improved outcomes. Potential treatment-emergent AEs need to be considered.

Developing Treatment Plans for Injectable Preventive Therapies

As of this writing, there are 4 injectable preventive therapies for migraine marketed in the United States: onabotulinumtoxinA and 3 monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) (fremanezumab, galcanezumab) or the CGRP receptor (erenumab).[39–43] OnabotulinumtoxinA is approved for chronic migraine, and erenumab, fremanezumab, and galcanezumab are approved for episodic and chronic migraine. While the principles of preventive therapy for oral preventives generally apply to injectable preventives, there are several notable points of contrast. First, there is no need for gradual dose escalation. The optimal dose of onabotulinumtoxinA is 155 units, and it is given as the initial dose. Erenumab is available in 2 doses (70 mg and 140 mg), either of which can be used as a starting dose. Fremanezumab is supplied in 2 doses, 225 mg and 675 mg, to support monthly and quarterly dose regimens, respectively,[44] and galcanezumab is provided in a 120 mg dose intended for monthly use following an initial loading dose of 240 mg.[45] The lack of need for slow dose escalation, the rapid onset of therapeutic benefits, and the favorable tolerability profiles are advantages that injectable therapies have in common. In the section on emerging therapies, we will discuss the use of these approved injectable therapies and the likely role of emerging treatments, including CGRP-targeted therapies.

Measuring Response to Preventive Treatment

Determining the efficacy and tolerability of preventive treatment is a patient-driven decision that may not exactly mirror the endpoints used in clinical trials. In general, a significant reduction (eg, 50%) in MHDs is a useful benchmark in both clinical trials and practice.[46] However, efficacy is variable between patients, and a successful therapeutic outcome depends not only on a reduction in MHD frequency, but also on the persistence and severity of pain and associated symptoms, level of disability, and functional capacity. Therefore, patient-centric and validated outcome measures that evaluate the effect of treatment on functional capacity, disability, and quality of life are important for determining whether meaningful change has occurred and, often, guiding clinical decision-making with respect to changes in dose, adding additional preventive treatment, or switching to an alternative treatment. Examples of these measures are included in Appendix A.