Preventive Therapy, Chronic Migraine

Case Study Part 1

Episodic MigraineNK is a 48-year-old female with a 6-year headache history initially diagnosed as low episodic migraine without aura. She previously experienced between 3 to 7 headache episodes per month lasting 4-5 hours, with typical features of migraine including pulsating headache, accompanying nausea, and limited ability to engage in any physical activity during these occurrences. She was initially treated with oral sumatriptan 50 mg, increased after 3 months to sumatriptan 100 mg.

The patient states she had been doing well on this management plan until 6 months ago when she underwent a total hysterectomy with elective bilateral salpingo-oophorectomy because of a 2-year history of severe menorrhagia from multiple uterine fibroid tumors and a family history of ovarian cancer. Since the surgery, the patient has had a substantial increase in the frequency and severity of her migraines, with the episodes increasing to 8 to 10 migraine days per month and now 15-18 migraine headache days per month over the past 4 months, with most of these attacks fulfilling the criteria for migraine without aura and lasting 6 to 8 hours at a time.

Challenge Question 1

On the basis of her history and current information, what type of migraine is this patient experiencing at this point in time?

While the patient's migraine history prior to her surgery was most suggestive of low frequency episodic migraine (LFEM), her current migraine pattern is now most suggestive of chronic migraine. 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.


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 2

Upon further questioning, NK states that while she previously only experienced mild side effects using sumatriptan 100 mg (mild nausea and flushing), she now states that she experiences dizziness and more severe nausea and sometimes vomiting with the agent, and she is now reluctant to use it. She has attempted to treat her headache episodes mostly with ibuprofen without much success, using sumatriptan only when her symptoms are truly severe. She is very upset about the current state of her migraines.

Because of the severity, frequency, and chronicity of her migraine episodes, NK was started on preventive therapy with oral topiramate titrated to 100 mg twice daily. However, when she returned for a 2-month follow-up appointment, she complained of marked gastrointestinal symptoms with this agent, including loss of appetite and diarrhea, leading to a 7-pound weight loss since her last visit. She even tried sprinkling the topiramate over food at her clinician's suggestion, but the side effects continued. Because of this, she has not been adherent to preventive therapy and is still experiencing 12-15 migraine episode days per month. She is very agitated and anxious about the current state of her migraines and complains that no one is really helping her. She asks if there isn't a better way to prevent her migraines that would not cause so much gastrointestinal upset.

Challenge Question 2

Approximately what median percentage of patients with migraine have been found to be noncompliant with preventive therapy?

Compliance with and adherence to migraine therapy is critical to optimal management. However, patients with migraine often delay taking their prescribed treatments or discontinue them entirely. Patients often make treatment decisions on how they view a particular therapy, especially as safe vs unsafe, and those who view a treatment as potentially unsafe are more likely to be noncompliant/nonadherent with therapy.1 Lack of adherence may occur with both acute or preventive therapy.1,2 In fact, a recent study found that only a median 24% of patient (range of 16% to 56%) are actually adherent to their preventive migraine treatment over a 6–12-month period, and adherence rates lower further over time and with the complexity of any treatment regimen.2 Other data suggest that only 1 in 4 migraine patients complies with oral preventive therapy when it is required for 6 months, dropping to 1 in 5 patients when treatment duration extends to one year. It is known that adherence is related strongly to both drug tolerability and efficacy, highlighting the need for novel and improved antimigraine agents to optimize therapy and improve patient experiences and compliance/adherence to treatment, including via new routes of administration for therapy.3,4

One potential option for relieving the gastrointestinal side effects associated with oral migraine therapies is parenteral administration. Continuous investigation is now underway for emerging parenterally administered monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway that has been proposed as a crucial target area in the pathophysiology of migraine

Challenge Question 3

All of the following emerging anti-CGRP agents for preventive therapy are administered via subcutaneous (SC) injection in clinical trials EXCEPT:

Monoclonal antibodies against CGRP erenumab, eptinezumab, fremanezumab, and galcanezumab are currently in development. There have been several phase 1 and 2 trials, and preliminary results of phase 3 trials have shown a good safety/tolerability profile and efficacy in migraine prevention, especially in high frequent episodic and chronic forms. Of these, 3 drugs are administered by SC injection, namely erenumab, fremanezumab, and galcanezumab. In comparison, eptinezumab has been studied using intravenous infusion. Further data, including phase 3 data, is highly anticipated for this new class of therapy for the migraineur affected by more severe symptoms and greater frequency of migraine episodes.

Shared decision-making (SDM) may help with medication compliance, adherence, and overall patient management in migraine. SDM is a process where patients and clinicians jointly participate in the decision-making process for the patient's health care and management. Using SDM, the clinicians and patients may discuss and assess treatment options and their risks and benefits, taking into account the individual patient's values, preferences for treatment, and other circumstances that may impact therapy. SMD provides a pathway and framework to enhance the clinician/patient relationship and improve communication and collaboration in therapy by reviewing management options together.5

SDM may not only involve the patient and clinician, but also the patient's family or caregivers and others involved in their management, all together comprising a decision team. All members of this team must understand the process and the goals for migraine management and agree that the patient's preferences and values must predominate. The ultimate goal of SDM is to make treatment decisions together that align with the patient’s needs and goals of treatment. Consistent and clear communication, and provision of the time needed for complete understanding is paramount for the decision team members to come to an understanding of the best steps forward in therapy to optimize patient management and treatment outcomes.6


  1. Katić GJ, Krause SJ, Tepper SJ, et al. Adherence to acute migraine medication: What does it mean, why does it matter. Headache. 2010;50(1):117-129.
  2. Seng E, Rains J, Nicholson R, et al. Improving Medication Adherence in Migraine Treatment. Curr Pain Headache Rep. 2015;19:24.
  3. 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].
  4. Hepp Z, Dodick DW, Varon SF, et al. Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia. 2015;35(6):478-488.
  5. Hoffman T, Légaré F, Simmons MB, et al. Shared decision making: what do clinicians need to know and why should they bother? MJA. 2014;201(1):35-39.
  6. Kon A. The shared decision-making continuum. JAMA. 2010;304(8):903-904.