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Bentsen L, Jensen R. Mirtazapine is effective in the prophylactic treatment of chronic tension-type headache. Neurology. 2004;62:1706-1711.

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 × intensity), was lower during treatment with mirtazapine (843) than during treatment with placebo (1275) (P= .01). Mirtazapine also reduced the secondary efficacy variables headache frequency (P= .005), headache duration (P= .03), and headache intensity (P= .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.

Comment: I am happy to see these results on mirtazepine for chronic tension-type headache (CTTH), and I look forward to prescribing it for daily headache, despite its occasional adverse events of weight gain and somnolence, similar to amitriptyline. It is probably not quite right to state, as the authors did, that “the tricyclic antidepressant amitriptyline is the only drug with prophylactic efficacy for CTTH.” For example, here are two randomized controlled studies suggesting efficacy for two very different medications for CTTH:

Saper JR, Silberstein SD, Lake AE III, Winters ME. Double-blind trial of fluoxetine: chronic daily headache and migraine. Headache. 1994;34:497-502.

Saper JR, Lake AE III, Cantrell DT, Winner PK, White JR. Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled, multicenter outcome study. Headache. 2002;42:470-482.—Stewart J. Tepper
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Document Type: Research Article

Publication date: November 1, 2004

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