Headache Drugs Logo Robbins Headache Clinic
Home | About Dr. Robbins | Archived Articles | Headache Books | Topic Index | Links  

Back to List


Treatment-Refractory Migraine: The Case for Opioid Therapy
John F. Rothrock, M.D.
Posted: July 2008  
Headache  2008;48:850-854

Few physicians are enthusiastic at the prospect of prescribing opioids for the treatment of acute or chronic pain, and for a variety of reasons, there has existed a particular bias against the use of these medications amongst clinicians who subspecialize in headache medicine.

Whatever inherent bias an individual physician harbors against the prescription of opioids may be reinforced by the very real potential for addiction associated with this class of drugs; i.e. "drug seeking behavior", and that opioid therapy both may obstruct the efficacy of more conventional headache treatments and produce an unfavorable long-term outcome. Faced with an environment so seemingly hostile, why should a physician prescribe patient-administered opioids for the treatment of migraine headache?

Until quite recently, what we now term chronic migraine (CM) has languished as the largely forgotten stepchild of headache medicine...an oversight ironic if only for the fact it is individuals afflicted with this disorder who make up the greatest proportion of patients presenting to centers specifically devoted to headache evaluation and treatment. As many as 8 million Americans suffer from CM, and not surprisingly it is this segment of the migraine population that suffers the greatest migraine-related disability and accounts for a disproportionate share of the direct costs attributable to migraine diagnosis and treatment.

Until recently, the research protocols for clinical trials investigating new prophylactic agents for migraine systematically excluded patients with the chronic variant of this primary headache disorder. Thus, clinicians who seek to treat CM must do so with an arsenal virtually bare of evidence-based therapies. While overuse of symptomatic medication (and, by inference, medication overuse headache) is common in this population, and although some patients may respond positively to termination of such overuse, treatment with topiramate or other prophylactic agents routinely used for less pervasive forms of migraine or to treatment of comorbid conditions such as depression or sleep apnea, there still exists a sizable subpopulation of patients with treatment-refractory CM.

Saper et al employed a variety of opioids for continuous (scheduled) opioid therapy, including both short- and long-acting drugs. In contrast, methadone was the only opioid prescribed to our subject population for chronic scheduled use, and it was administered according to a uniform and prospectively derived dosing schedule. Especially when compared with the short-acting opioids, methadone may be less likely to produce euphoria, tolerance, and psychological addiction. In fairness, however, it should be noted that some investigators have found no significant differences between long- vs. short-acting opioids in efficacy rates, the development of tolerance or the prevalence of "problem drug behavior," and in his study of long-acting opioids (i.e. methadone and oxycodone) for the treatment of chronic daily headache, Robbins reported a positive long-term treatment response in only "a very small minority."

In what some may take to be an interesting side note, we have found that patients whose CM responds favorably to methadone experience that response at a relatively low dose (2.5 mg. to 10 mg. TID), while patients who report no or minimal improvement at a low dose fail to experience a positive treatment response if the dose is advanced beyond 10 mg. TID. On a more ominous note, virtually all of our long-term responders rapidly have relapsed to CM following attempts to taper off methadone, and this has occurred independent of the dose or duration of methadone treatment, the duration of the taper period or the use/lack of use of concomitant "conventional" prophylactic therapy. Especially given the drug’s reported association with an increased risk of mortality even when prescribed (and taken) at relatively low doses, the prospect of chronic, indefinite treatment with methadone is difficult to embrace with any enthusiasm.

There remains the issue of whether it should be considered advisable to prescribe short-acting opioids to selected patients for self-administered treatment of acute, severe migraine headaches. Once again, the obvious response is: what is the alternative? For many patients with migraine, treatment with triptans or ergotamines may be contraindicated or simply ineffective; even patients whose migraines typically respond to an oral, intranasal or injectable triptan or ergotamine may experience attacks that have progressed pathophysiologically to the point where their usual symptomatic therapy is ineffective. In such instances, self-administration of an oral nonsteroidal anti-inflammatory agent, a butalbital-containing compound or another non-opioid symptomatic medication is unlikely to provide much benefit. As an alternative either to leaving the patient to suffer or present to an emergency room (with the associated expense and inconvenience), judicious prescription of a short-acting opioid to use for "rescue" from severe migraine headache would appear both sensible and medically appropriate.