Subscription is FREE for qualified healthcare professionals in the US.

Difficult to Treat Chronic Migraine: Outpatient Medication Approaches

Refractory chronic migraine often is a disabling, debilitating, and challenging illness. Patients who have medication overuse headache or psychological comorbidities require a combination of therapeutic approaches.
Page 1 of 7

Patients with refractory chronic migraine (RCM) experience a great deal of disability and loss of their quality of life. Chronic migraine occurs in approximately 2% of the population, but we do not know the epidemiology or rate of occurrence of RCM.

To provide a framework for other physicians and health care providers, the Refractory Headache Special Interest Section of the American Headache Society was formed in 2001. This committee of headache specialists seeks to define a standard of diagnosis for health practitioners and raise awareness of improved treatments for headache.

The definition of chronic migraine (CM) is outlined in Table 1, and the current proposed criteria for the definition of RCM is a work in progress and is summarized in Table 2.1,2 The committee may want to add modifiers related to the degree of refractoriness (mild, moderate, or severe). In some patients, RCM improves or resolves over time, whereas in others it worsens. These differences need to be addressed in the definition.3

Challenges of Refractory Migraine

RCM presents a number of major challenges, with each challenge necessitating a change in approach.3 These challenges include:

  • What role does disability play, and should disability help to define RCM?
  • What constitutes resistance to treatment(s)?
  • There are no accepted, identifiable biological marker(s) for RCM. Therefore, how does one diagnose RCM?
  • The degree of disease can change over time, improving or worsening. What role does the varying severity play?
  • There are various subsets of RCM—post-traumatic headache, RCM with or without medication overuse headache (MOH), RCM with or without major psychiatric comorbidities, etc. How is the diagnosis and treatment affected by these subsets?
  • How does the treatment differ for various ages: adolescent vs. young adult vs. middle age vs. older ages?


We are just beginning to look beneath the surface of what causes RCM.4 Some of the issues include:

  • What is the role of genetics in drug resistance and inheritance of chronic headaches?
  • What structural changes (in white matter or iron deposition) play a role?
  • What role does central sensitization and neuroplasticity play?
  • How much involvement is peripheral vs. central nervous system?
  • How does MOH affect the structure and function of the nervous system?
  • What is the physiologic impact of psychiatric comorbidities? Do depression and/or anxiety fuel the headaches?

Continuing research is critical to answer these questions.

Several risk factors are posited to drive the development of RCM. These include lifestyle issues such as medication overuse, sleep habits, caffeine overuse, and obesity.5 While pharmacotherapy may be the cornerstone of treatment, other modalities are no less important. The patient must manage his or her triggers with regards to sleep, food, and caffeine intake. Exercise and weight reduction are encouraged. Stress, another major trigger, may be relieved by practicing biofeedback and/or yoga. Depending on the origin of the pain, physical therapy and massage may help. Problems with the teeth, jaw, eyes, and neck should be addressed.

Medication Overuse Headache

Medication overuse headache is a critical issue that must be addressed early in the treatment of any form of headache.6 The overuse of abortive migraine medication, used at the onset of a headache, is a major risk factor for the progression of migraine into RCM. Some patients have medication overuse without an increase in headache. In others, overuse of abortive medications is the principal cause of the headaches.

The criteria for diagnosing MOH are listed in Table 3. Note that the headache progresses, instead of subsides, over time, and the calls for prescription refills will become more frequent with the progression. When treating patients with MOH, the offending drugs will need to be withdrawn or limited. While we do not know with any certainty the percentage of RCM patients in whom MOH is a major contributor, we know that MOH should be one of the first considerations when a patient presents with worsening headaches.

While medication overuse is common, not all overusers suffer from increased headaches as a result of the abortive medications. The current definition of MOH conflates medication overuse with MOH, and, as a result, many patients are incorrectly labeled as having MOH.

Treatments for RCM

There is no algorithm for migraine treatment. The choices of medication will vary for each patient, depending on headache severity and comorbidities. For a RCM patient, the choice of therapy depends on a number of variables, including age, psychiatric comorbidities (For more on psychiatric comorbities, click here), tendency towards addiction, sleep, medical conditions, etc. Comorbidities often steer where we go with medications: conditions such as irritable bowel syndrome (IBS), fatigue, and psychiatric conditions have to be considered. Of course, the familiarity and confidence with a particular therapy on the part of the treating physician plays a major role in selection. It also is crucial to resolve medication overuse, and eliminate rebound in all RCM patients. For the remainder of this article, the author has highlighted a number of possible approaches (opioids, onobotulinum toxin, daily or frequent triptans, stimulants, monamine oxidase inhibitors, injections, and miscellaneous), some of which may be combined.


In my practice, long-acting opioids are the most commonly used approach for RCM. The best candidate for long-acting opioids is the person who has done well on short-acting opioids and who does not have characteristics of a personality disorder (PD).

Phases in Opioid Use

There are 3 distinct phases in the use of opioids. The first phase is the initiation of treatment. This includes the initial screening and risk assessment, the doctor’s decision as to which opioid to use, and the doctor-patient discussion and signing of an opioid agreement. Prior to initiation of long-acting opioids, an assessment of the following should be done: pain level, moods, social and family functioning, work status, physical functioning, and activities of daily living.7

The intermediate phase is comprised of the diligent monitoring of the patient while he/she is on the opioid. This must include ongoing assessment of the patient’s pain level and overall functioning, with a watchful eye for signs of abuse. On return visits, the physical exam needs to assess for slurring of words, abnormal gait, and pupillary abnormalities. Do not assume that low-risk patients will never abuse the opioids. During the maintenance phase of opioid prescribing, it is remarkable how many seemingly low-risk patients misuse the drugs.

Last updated on: May 18, 2015
First published on: September 1, 2014