Case Study Part 1
MR is a 40-year-old white female with a previous history of recurrent headaches, originally diagnosed 12 months earlier as migraine without aura. The patient has returned to her primary care physician for medical followup of her migraines and to discuss options for therapy. After her first evaluation and diagnosis, the patient was initially prescribed oral sumatriptan 50 mg for acute migraine episodes. However, at her last clinical visit 6 months ago, she complained that she did not experience complete relief with this prescription, and her dosage of sumatriptan was increased to 100 mg with the patient instructed to initiate therapy with this agent immediately once her headache episodes start.
The patient now reports that sumatriptan is working “pretty well” for most of her attacks. However, her current insurance coverage limits her to 9 sumatriptan tablets per month and she feels that is not enough. She is averaging 2-3 moderate-to-severe migraine headaches per month, and 2-3 somewhat less severe headaches per week. Because of this she “saves” her sumatriptan tablets for her more severe headaches and treats the less severe episodes with either over-the counter (OTC) ibuprofen or the combination of OTC acetaminophen/aspirin/caffeine (Excedrin). The patient now requests that a quantity override be requested of her insurance carrier so that she can get 18 sumatriptan tablets per month instead of 9. She is not taking any migraine preventive medications, denies any change in her general health, and claims she cannot identify any new triggers for her migraines.
Challenge Question 1
The type of questioning a clinician uses for each patient with migraine may help or hinder in determining exactly how seriously migraine episodes are affecting that patient, potentially impacting decisions on adjusting therapy. The American Migraine Communications Study involved health care practitioners who were managing a high volume of migraineurs, recruiting 60 patients with frequent migraine and assessing the number and type of questions asked of them on migraine frequency and impairment. Results showed that the vast majority (91%) of clinicians involved used migraine-specific questions that were closed-ended or short answer questions, concentrating on headache frequency instead of the level of impairment each individual patient actually experienced during their migraine episodes. In contrast, post-visit interviews conducted by researchers using more open-ended questions resulted in the same patients providing information on the level of impairment they experienced with their migraine that was not disclosed during the clinical visits. Post-visit, 55% of clinician-patient pairs were found to be misaligned regarding actual headache frequency, with 51% misaligned on impairment. Of the total 20 patients (33%) who were candidates for preventive therapy for migraine, 80% did not receive it, and 50% of their visits even lacked discussion of migraine prevention between the clinician and patient.
Sample open-ended questions include the following:
- How do migraines make you feel, even when you aren't having one?
- How do your migraines impact your daily life/activities of daily living?
- Can you describe the impact migraines have on your work, family, and social life?
- How does having an acute episode make you feel?
- Describe how your migraines affect you between attacks?
Asking questions in an open-ended way designed to provide more detailed and emotional responses can lead to a more complete and accurate picture of how disabling migraines may be for individual patients, allowing better assessment of disease severity and potentially changing therapy and management plans.
Lipton R, Hahn S, Cady R, et al. In-office Discussions of Migraine; Results from the American Migraine Communications Study. J Gen Intern Med. 2008;23(8):1145-1151.
Case Study Part 2
When further questioned about how her headache episodes impact her daily living, the patient states that on the more severe headache days, the pain is of severe intensity, and she has to stay in a darkened room until her headache passes if treatment doesn't work. However, on the days when she describes her headaches as less severe, they still last approximately 2-3 hours and are frequently accompanied by nausea and sometimes prevent her from taking her daily walk for exercise.
Challenge Question 2
Overall, the patient's 2 to 3 “smaller” headaches per week and 2-3 “more severe” headaches that last 48 hours if unsuccessfully treated add up to a total number of headache days averaging 13-14 days per month. Episodic migraine is characterized by headaches that occur on fewer than 15 days per month.1 The features of chronic migraine include headache occurring on 15 or more days of the month for more than 3 months, which has the features of migraine headache on at least 8 days per month. In the case of a patient diagnosed with migraine without aura, the following criteria must also be fulfilled for a diagnosis of chronic migraine, namely headache lasting 4 to 72 hours whether untreated or treated successfully, and that the pain is unilateral, pulsating, of moderate-to-severe intensity, and aggravated by or causing avoidance of routine physical activity to meet the criteria for chronic migraine.2
- Lipton RB, Silberstein SD. Episodic and chronic migraine headache: Breaking down barriers to treatment and prevention. Headache. 2015;55(Suppl 2):103-122.
- Headache Classification Committee of the International Headache Society. The international classification of headache disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629-808.
Case Study Part 3
Upon further questioning, MR admits to stress with her mother-in-law having health issues, including a recent broken hip requiring surgery and placement in a rehabilitation facility. MR and her husband are not sure if it will be safe for her mother-in-law to return to living alone in her home because of her surgery and the fact that she has been widowed for several years and appears to be more forgetful in recent months. MR’s children are 17 and 20 years of age. The 20-year-old is in college and the 17-year-old is looking at colleges and is considering several expensive out-of-state universities. MR is worried about college costs as she and her husband are paying all tuition and living expenses for their older child. In addition, her mother-in-law may need financial assistance as she has limited funds. MR admits that this mounting stress in her life may be contributing to her increasing headache frequency and severity, leading to her asking for an insurance override to obtain more acute therapy doses. Her clinician initiates a discussion of preventive therapy/prophylaxis instead and the potential benefits of this type of therapy for the patient. Preventive therapy can enhance a patient’s response to abortive therapy, resulting ultimately in a better quality of life. Prevention should not be limited to pharmacologic treatment. Non-pharmacologic approaches may include cognitive behavioral therapy, relaxation techniques, and biofeedback. Despite a recent consensus outline for daily pharmacologic treatment, determining appropriate and effective, preventive therapy remains a challenge for health care providers.
Challenge Question 3
Preventive therapy can enhance a patient’s response to abortive therapy, resulting ultimately in a better quality of life. Prevention should not be limited to pharmacologic treatment. Non-pharmacologic approaches may include cognitive behavioral therapy, relaxation techniques, and biofeedback.
Approximately 45% of patients receiving preventive therapy will experience a reduction in the mean monthly frequency of migraine attacks by ≥50%. However, this approach is underutilized and considerable variability among physicians exists in adherence to accepted guidelines.1 The US Headache Consortium recommend, based on expert consensus, considering prophylactic therapy whenever one of the following is present: a headache profile with a significant impact on daily life, having a contraindication to or an adverse effect with acute treatment, risk of medication overuse headache (MOH), patient preference, and the presence of one of the uncommon, unpleasant migraine varieties such as hemiplegic migraine, basilar migraine, or migrainous infarction.2 When deciding on preventive treatment, a care provider should consider the frequency, severity, and disability of migraines. The selection of a drug should be based upon level of evidence for efficacy, adverse effect profile, and patient comorbidities. Drugs should be started at a low dose, raised to optimal dosage, and continued for a period of 2-3 months. Patients should keep headache diaries for progress to be assessed.3 However, it is estimated that 1 in every 4 migraineurs who are candidates for migraine prophylaxis do not receive it.3-5
- Silberstein SD, Holland S, Freitag F, et al.; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17):1337-1345.
- Al-Quliti KW, Assaedi ES. New advances in prevention of migraine: Review of current practice and recent advances. Neurosciences. 2016;21(3):207-214.
- Estemalik E, Tepper S. Preventive treatment in migraine and the new US guidelines. Neuropsychiatr Dis Treat. 2013;9:709-720.
- Lipton RB, Silberstein SD. Episodic and chronic migraine headache: Breaking down barriers to optimal treatment and prevention. Headache. 2015; 55 Suppl 2():103-122; quiz 123-126
- Diener HC, Solbach K, Holle D, et al.Integrated care for chronic migraine patients: Epidemiology, burden, diagnosis and treatment options. Clin Med (Lond). 2015;15(4):344-350.
Challenge Question 4
Prophylactic therapy is indicated when attacks occur more than one to two attacks per week for more than 48 hours, or cause significant functional impairment and disability impacting quality of life. It is also considered if symptomatic treatment provides inadequate relief, unacceptable side effects, and to prevent progressive disease. Despite the unmet need for prophylaxis of migraine, there are few new drugs that are specifically approved for this indication.
The various classes of medication for preventive therapy of migraine include beta-blockers, calcium channel antagonists, antidepressants, anticonvulsants, and nonsteroidal anti-inflammatory drugs (NDAIDs) The four medications that are FDA-approved for prevention of episodic migraine are topiramate, divalproex sodium, propranolol, and timolol, and these agents have been designated as Level A/established as effective treatments in the most recent American Headache Society/American Academy of Neurology Guidelines and also Canadian guidelines for prevention of episodic migraine. Multiple other agents have evidence for their use, including amitriptyline, venlafaxine, atenolol, and nadolal.1,2
Choice of medications used in the preventive setting should be tailored to patient characteristics, patient preferences and headache profile, as well as the presence or absence of comorbid conditions.
Challenge Question 5
While there are only four agents that are currently FDA-approved for preventive therapy in episodic migraine, multiple other agents are undergoing investigation.3 The clinical research and drug development landscape for migraine is evolving, highlighting the potential for major changes to existing treatment paradigms, especially in the area of preventive treatments and therapeutic strategies that will be effective, not only in providing analgesia, but also in reducing the progression from episodic to chronic migraine.
Four anti-CGRP mAbs are currently in development. Three of them are humanized mAbs that are designed to remove excess CGRP by blocking the CGRP ligand: ALD403 (Alder Pharmaceuticals), LY2951742 (Eli Lilly & Co.), and TEV-48125 (formerly LBR-101, Teva Pharmaceuticals). The other, AMG 334 (Amgen), is a fully human mAb that targets the CGRP receptor itself to interfere with CGRP signaling. So far, research has shown a reassuring overall safety profile of anti-CGRP mAbs, with no vasoconstrictor effects. The future introduction of mAbs for treatment of migraine may represent a "turning point" for prevention of migraine similar to that of the use of triptans for treatment of acute episodes.3,4
In summary, management of patients with headaches hinges first on achieving an accurate diagnosis. It is crucial for clinicians to establish a therapeutic partnership with the patient before starting preventive therapy and communicate clear expectations regarding the timing of therapy, the potential magnitude of therapeutic benefit, along with a comprehensive migraine management plan that includes long-term goals and regular follow-up.5
Enter into a therapeutic alliance with your patient to decide what are the best options for them. When considering preventive medication, take into account individual patient characteristics and preferences when selecting from the many available options. Finally, you want to reevaluate the efficacy and tolerability of your medications on all follow‐up visits with your patient.
- Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults. Neurology. 2012;78(17):1337-1345.
- Loder E, Burch R, Rizzoli P. The 2012 AHS/AAN Guidelines for Prevention of Episodic Migraine: A Summary and Comparison With Other Recent Clinical Practice Guidelines. Headache. 2012; 52(6):930-945.
- Giamberardino MA, Affaitati G, Curto M, et al. Anti-CGRP monoclonal antibodies in migraine: Current perspectives. Inter Emerg Med. 2016;11(8):1045-1057.
- Mitsikostas, DD, Reuter U. Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: comparisons across randomized controlled studies. Curr Opin Neurol. 2017 Feb 24. doi: 10.1097/WCO.0000000000000438. [Epub ahead of print].
- Rapoport AM. How to choose a preventive medication in migraine. Available at: https://americanheadachesociety.org/wp-content/uploads/2016/07/Alan_Rapoport_-_Migraine_Prevention_Medications.pdf.