Medication overuse headache (MOH) is one of the most frequent causes of chronic headache among patients in tertiary headache centers, and it is now recognized as a serious public health problem. According to epidemiologic studies in the United States, Spain, and Germany, 0.5% of the population has experienced MOH. It is caused by the frequent or daily intake of analgesics, combination analgesics, barbiturates, opioids, ergots, triptans, or caffeine.
Although physicians agree on the significance of MOH, there is no consensus on how to treat the condition. Some physicians believe that drug withdrawal alone should be used as treatment, while others prefer a multifaceted approach. Proponents of each view made their case in a scientific debate at the 49th Annual Scientific Meeting of the American Headache Society.
According to Hans-Cristoph Diener, MD, PhD, patients can achieve a positive outcome with drug withdrawal alone. "Basically, all textbooks and review articles claim that long-term success after withdrawal therapy can only be achieved
if treatment is continued with behavioral therapy and use of prophylactic medication," said Dr. Diener. "This claim, however, is not substantiated by any scientific evidence." Dr. Diener is Chairman of the Department of Neurology and the Headache Center at the University Duisburg-Essen, Germany.
In a recent randomized study from Italy, Rossi and colleagues compared the effectiveness of strong advice to withdraw from the overused medication with the effectiveness of two structured pharmacologic detoxification strategies in 120 patients diagnosed with probable MOH plus migraine. Patients were randomized into three groups: group A received only intensive advice to withdraw from the overused medication; group A attended a standard outpatient detoxification program that included advice, prednisone, and preventive treatment; and group C underwent a standard inpatient withdrawal program (everything that group B received plus fluid replacement and antiemetics). Detoxification was successful in 77.5% of patients in group A, 71.7% of patients in group B, and 76.9% of patients in group C.
According to Dr. Diener, drug withdrawal may not even be needed. He recently conducted a study to determine whether it was necessary for patients with MOH to undergo drug withdrawal or if these patients could be treated effectively with preventive therapy. The study included patients between ages 18 and 65 who had experienced chronic migraine (15 or more monthly migraine days) for three or more months before entering the study, with 12 or more migraine days during the four-week baseline phase. These patients were randomized to receive topiramate or placebo in a 16-week, double-blind trial. Seventy-eight percent of the patients fulfilled the criteria of MOH. The primary efficacy measure was the change in the number of migraine days from the 28-day baseline phase to the last 28 days of the double-blind phase in the intent-to-treat population.
The study included 59 patients: 32 received topiramate, and 27 received placebo. Topiramate significantly reduced the mean number of monthly migraine days, compared to placebo.
"This trial demonstrates that topiramate is effective and reasonably well tolerated when used for the preventive treatment of patients with chronic migraine, even in the presence of medication overuse," said Dr. Diener. "For most patients with medication overuse headache, counseling how to perform drug withdrawal at home or outpatient drug withdrawal is enough, and patients who relapse can be treated again."
Dr. Diener also pointed out that the situation might be different in the US compared with Europe. Combination analgesics containing barbiturates or opioids are banned in most European countries for the treatment of headache.
In contrast, Joel R. Saper, M.D., believes that although drug withdrawal alone may occasionally be successful, most patients require additional treatment. "In the broadest context, it is shortsighted to define a positive outcome as stopping one episode of MOH," said Dr. Saper. "MOH does not occur in isolation. It is a chronic vulnerability linked pathophysiologically and behaviorally to migraine and related disorders. There is evidence that receptor changes live well beyond the actual drug use, so it demands a multifaceted approach," noted Dr. Saper, Director of the Michigan Headache & Neurological Institute in Ann Arbor and Clinical Professor of Medicine at Michigan State University in East Lansing.
Dr. Saper explained that MOH has biobehavioral influences. "It is not simply the overuse of medication," he said. "There is a behavior factor that characterizes many, if not most, of the cases that we see in the United States. MOH is a pharmacokinetic up-regulation of the nociceptive system. There are genetic factors, neuroplastic factors, and neurobehavioral factors."
Because not all patients with frequent headaches misuse their drugs, Dr. Saper said that it seems reasonable to suggest that the combination of behavioral disturbance and frequent headache likely underlies the overuse pattern in many, if not most, patients. He pointed out that discontinuing a drug in patients with MOH does not discontinue the pathology of frequent headaches. "At best, it takes one back to baseline, which was the start of the problem in the first place," he said.
Dr. Saper emphasized that it is critical to provide rescue drugs during withdrawal and beyond. "It is of practical value to offer a preventive agent that may eventually have a primary effect or at least a placebo effect, giving the fearful, anxious patient the confidence to complete the therapy," he said. "During withdrawal from some drugs like barbiturates and some opioids, there is escalation of emotional and behavioral events -- not just pain. Additionally, pain all over the body can become worsened." These patients also can experience autonomic signs and symptoms, insomnia and sleep disturbance, and neuromuscular symptoms. In addition, there are very high relapse rates, even in a non-opioid-using population.
Dr. Saper recommends the reclassification of MOH. Type 1 would be MOH that is unaccompanied by confounding behavioral disturbances and the use of simple analgesic triptans, and type 2 would be MOH confounded by significant behavioral disturbance and/or opioid use and dependence. "By reclassifying MOH, we may address the fundamental issue of this debate," he said.