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Old and New Drug Therapies for Chronic Headache

Findings of two new studies send a pessimistic message regarding treatment of this condition.

For patients and their clinicians, treatment of chronic headaches can be frustrating. In two studies, investigators look at a new antidepressant, mirtazapine (Remeron), and an old remedy of last resort, opioids.

The first study -- a randomized, double-blind, crossover trial of mirtazapine -- included 24 nondepressed Danish patients with chronic tension-type headaches who hadn't responded to numerous other treatments. Each patient received 8-week courses of mirtazapine and placebo, separated by a 2-week washout period. According to a quantitative measure that combined daily headache duration and severity, mirtazapine reduced symptoms by 34% compared with placebo -- a significant difference. Drowsiness, dizziness, and weight gain were more common with mirtazapine than with placebo, but these differences didn't reach statistical significance.

The second study, from a Michigan headache center, included 160 patients with "intractable daily head pain"; all had failed to respond to previous standard therapies. The treatment program consisted of titrated opioid therapy, frequent office visits, a signed agreement comprising rules governing patients' use of opioids, and behavioral elements. During the first 3 years of follow-up, 90 patients dropped out for various reasons. Seventy patients continued long-term opioid therapy (mostly sustained-release morphine, sustained-release oxycodone, or methadone). Only 41 of the 160 patients (26%) were considered to be responders, according to a headache-severity index. Of the 70 long-term opioid users, 35 violated their written agreements at least once.

Comment: Taken together, these findings send a rather pessimistic message regarding drug treatment of intractable chronic headache. In the mirtazapine study, improvement was modest, side effects were frequent, and treatment duration was quite brief. Results from the opioid study suggest that few such patients will respond satisfactorily to long-acting opioids, even in a highly structured referral program.

— Allan S. Brett, MD

Published in Journal Watch General Medicine June 25, 2004

Citation(s):

Bendtsen L and Jensen R. Mirtazapine is effective in the prophylactic treatment of chronic tension-type headache. Neurology 2004 May 25; 62:1706-11.

• Original article (Subscription may be required)
• Medline abstract (Free)

Saper JR et al. Daily scheduled opioids for intractable head pain: Long-term observations of a treatment program. Neurology 2004 May 25; 62:1687-94.

• Original article (Subscription may be required)
• Medline abstract (Free)