Mirtazapine is effective in the prophylactic treatment of chronic tension-type headache.

BACKGROUND The tricyclic antidepressant amitriptyline is the only drug with prophylactic efficacy for chronic tension-type headache. However, amitriptyline is only moderately effective, with headache reduction of approximately 30%, and treatment is often hampered by side effects. Mirtazapine is a relatively new so-called noradrenergic and specific serotonergic antidepressant, which is more specific and therefore generally better tolerated. OBJECTIVE To evaluate the efficacy of mirtazapine. METHODS Twenty-four nondepressed patients with chronic tension-type headache were included in a randomized, double-blind, placebo-controlled, crossover trial. All patients had tried numerous other treatments. Mirtazapine 15 to 30 mg/day or placebo was each given for 8 weeks separated by a 2-week wash-out period. RESULTS Twenty-two patients completed the study. The primary efficacy variable, area-under-the-headache curve (AUC; duration x intensity), was lower during treatment with mirtazapine (843) than during treatment with placebo (1,275) (p = 0.01). Mirtazapine also reduced the secondary efficacy variables headache frequency (p = 0.005), headache duration (p = 0.03), and headache intensity (p = 0.03) and was well tolerated. CONCLUSIONS Mirtazapine reduced AUC by 34% more than placebo in difficult-to-treat patients. This finding is clinically relevant and may stimulate the development of prophylactic treatments with increased efficacy and fewer side effects for tension-type headache and other types of chronic pain.