Migraine and Its Connections in Neurology and Psychiatry

At the recent meeting in Hawaii of the American Academy of Neurology, we heard many positive comments about CNS Spectrums. We were also urged by the attending neurologists to try and include more articles and issues devoted to neurologic disease and mechanisms. Previously, we have had issues on epilepsy and stroke, and future issues are planned that will cover movement disorders, multiple sclerosis, child neurology, and Alzheimer's disease. We very much want and welcome both suggestions for neurological topics to which future issues may be dedicated and submission of unsolicited original research and review articles dealing with neurological topics. Our peer review process is quick and efficient. Accepted articles will be scheduled to appear as rapidly as possible. This issue, whose articles I will discuss out of the printed order, is devoted largely to a topic of interest to neurologists and psychiatrists alike—migraine. Four papers deal with various aspects of migraine headache, a common and often plaguing disorder that still mystifies scientists and often eludes response to therapy. It is not an easy condition to diagnose; unlike many neurologic disorders, but in common with most psychiatric illness, there are no definitive objective tests that can make a positive diagnosis of migraine headache. Rather, after ruling out other causes of headache, like brain tumor, the neurologist must rely largely on history. Sometimes, the elicitation of symptoms like an aura can be nearly pathognomonic, but more often migraine is a diagnosis of exclusion by history alone. Treatment relies on palliative measures, including a variety of analgesics, some of which have abuse potential, ergotamine, (3-blockers, anticonvulsants, and serotoninenhancing drugs. Antidepressants generally are not effective in treating migraine headache; in some patients they seem to help while in others they worsen the situation. Adding to this complexity, as Nancy C.P. Low, MD, MS, and Kathleen Ries Merikangas, PhD, of the National Institute of Mental Health, is the fact that migraine is highly comorbid with a host of other medical problems. These involve almost all organ systems and include psychiatric illness. Unfortunately, this penchant for co-occurrence with other disorders has not shed much light on the fundamental pathophysiology of migraine headache, but it does sometimes obscure the diagnosis. Their article is important as a reminder to think about migraine in patients with headache even in the face of multiple other problems. Two articles suggest possible new treatment approaches to migraine. Keith R. Edwards, MD, from the Neurological Research Center in Bennington, Vermont, and colleages, from various other locations, combine data from two single-site, double-blind, placebo-controlled trials of the anticonvulsant topiramate for migraine prophylaxis. Seventy patients were enrolled and the results were positive: overall, topiramate produced a lower 28-day migraine frequency than placebo. About five times as many patients responded to topiramate than to placebo, although the overall response rate to the active drug was low (35.3%). Topiramate-associated adverse events included paresthesia and memory impairment. As has been observed before, topiramate also caused appetite suppression and weight loss. As I am a consultant to the manufacturer of topiramate (and therefore did not participate in the review of this article), I will refrain here from making any conclusions except to say that future studies of topiramate will be of great interest. Nabih M. Ramadan, MD, from the Chicago Medical School argues convincingly in his paper that migraine headache may involve an abnormal activation of glutamatergic neuronal pathways and suggests that glutamate antagonists, which appear to work in animal models of migraine, might be useful therapeutically. This work provides both a mechanistic hypothesis and a suggestion for treatment approaches and deserves careful scrutiny by both investigators and clinicians. By contrast to these positive notes about therapeutics, William B. Young, MD, and colleagues from the Thomas Jefferson University Hospital provide data from a study of 50 patients with severe headache, most of who had migraine, who were admitted to an outpatient infusion center. Seventeen of these patients also had restless legs syndrome and these individuals turned out to have a very high risk of developing akathisia following administration of intravenous dopamine receptor blocking agents. The authors suggest that increased surveillance for restless legs syndrome in headache patients might be important prior to initiating therapy with dopamine receptor antagonists. A final paper in this issue deals with a completely separate topic, obsessive-compulsive disorder (OCD). Donatella Marazziti, MD, of the University of Pisa and an associate international editor of CNS Spectrums notes that about onethird of patients with OCD do not respond to serotonin reuptake inhibitor medications. Dr. Marazziti reports a positive experience with venlafaxine for such patients, a medication that blocks both serotonin and norepinephrine reuptake in a manner similar to clomipramine but with fewer adverse events. This is welcome news for clinicians and patients alike dealing with the often very hard to treat syndrome of OCD. Finally, I want to remind our readers that CNS Spectrums is now accepting letters to the editor. Please send them in! I