We often talk about the “difficult” headache patient This is the patient whose headaches are refractory to the “usual” pharmacologic and non-pharmacologic approaches. Their pain is often intractable and there are frequently overuse, misuse, and dependency issues. These are the patients who make frequent visits to the ER, have ongoing “compliance” issues, have seen many, many different providers, and have a variety of comorbid medical and psychiatric issues.

Usually, when such patients are characterized , their MMPI profile is that of the neurotic, with elevation of the first three scales – hypochondriasis, depression, and hysteria. Indeed, Matthew reported comorbid depression in more than 80% of chronic daily headache patients. Breslau found odds ratios of 4 or greater with dysthymia, major depression, mania, and bipolar disease. However, as Harold Wolf pointed out more than fifty years ago, “It is unprofitable to establish a separate category of illness to be defined as psychosomatic. Rather, a man’s nervous system is implicated in all categories of disease.”

What then, is the mechanism of comorbid headache and psychiatric conditions? Among the neurotransmitters involved in headache, monoamines are most prominent – particularly serotonin, dopamine, and norepinephrine. Additionally, endorphins, GABA and glutamate have all been implicated in the pathophysiology. Not surprisingly, these peptides also play a role in mood disorders, anxiety disorders, sleep disorders, eating disorders, and OCD. That there is a relationship between mood and pain should come as no surprise. It has been postulated that pain is augmented by the limbic system, and increased activity in the locus coeruleus and red nucleus (limbic system) has been demonstrated with positron emission tomography by Dodick, et al. The hippocampus has also been implicated in a variety of neuropsychiatric disorders, although not specifically in headache.

Evaluation of the psychiatric patient should seek to identify medical comorbidities, including migraine. Useful tools include Hamilton, Zung or Beck inventories, MADRS, PRIME-MD, PHQ-9, PHQ-2, MMPI, and of course, a good clinical evaluation. The MIDAS scale is a reliable screen for headache in this population. It is a quick assessment and the form can be downloaded from the internet.

Treatment goals for comorbid headache and psychiatric conditions are remarkably similar. We seek to remit all signs and symptoms, restor occupational and social function, reduce any acute risk of suicide, relapse or recurrence, and maximize long-term outcomes. This means we must go well beyond the short-term response we often see with the introduction of a new medicine. At the same time, we must monitor for worsening one condition as we focus on another.

While the major classes of antidepressants are generally safe in migraine, there are frequent idiosyncratic responses that worsen the headache. However, we must try to separate the coincident headache from causation by a new medication. Neuromodulation can also be achieved with non-pharmacologic approaches including vagus nerve, occipital nerve or deep brain stimulators, transcranial madnetic stimulation, and electroconvulsive therapy. In almost every circumstance, these therapies, both medicine based, and “invasive” should be coupled with cognitive and/or behavioral therapy to achieve a maximal and long-lasting effect.

Finally, a word should be said about the borderline patient. This is the patient characterized by impulsiveness, emotional dysregulation, and difficulty assessing self and others. Clinically, this is the patient who says “Thank God, I’ve found you! You are the only one who can help! And a month later says, “You’re no better than the others, I knew you’d do this to me!” When addressing comorbid issues with this kind of patient, particularly headache issues, it is important to address outcomes and expectations at the first visit, address limits and set boundaries, insist that psychotherapy be part of the headache treatment plan, and consider contracts for medications, refills, appointments, etc.

In summary, it is important to avoid discounting headache based on comorbid depression or other psychiatric diagnosis. While headache can, rarely, be part of a somatization or conversion, migraine is so ubiquitous in the population, that this circumstance should be viewed as the exception, rather than the rule. Similarly, treating migraine in a vacuum without allowing for the comorbidities, is an equally doomed proposition.

Dr. Robert Cowan is the founding medical director of the Keeler Center for the Study of Headache (Ojai, CA) and senior clinical research scientist in molecular neurobiology at Huntington Medical Research Institutes (Pasadena, CA). Dr. Cowan attended University of Southern California, Keck Medical School, completed a residency program at USC Department of Neurology and served on faculty there until 2000. He is Board Certified in the areas of: Psychiatry and Neurology and Pain Medicine. Dr. Cowan has published articles in various scientific journals, including the Journal of the American Medical Association and Headache. In addition, Dr. Cowan serves as national chair of the section on complementary and alternative medicine for the American Headache Society. He is Vice President of the Headache Cooperative of the Pacific and a fellow of the American Academy of Neurology. For more information about the Keeler Center, contact Brenda Mercado, MFT.