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

Neurology. 2004 May 25;62(10):1706-11. doi: 10.1212/01.wnl.0000127282.90920.8c.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Antagonists / adverse effects
  • Adrenergic alpha-Antagonists / therapeutic use*
  • Adult
  • Area Under Curve
  • Chronic Disease
  • Cross-Over Studies
  • Dizziness / chemically induced
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Mianserin / adverse effects
  • Mianserin / analogs & derivatives*
  • Mianserin / therapeutic use*
  • Middle Aged
  • Mirtazapine
  • Neurotransmitter Agents / metabolism
  • Pain Measurement
  • Receptors, Presynaptic / antagonists & inhibitors
  • Tension-Type Headache / drug therapy*
  • Treatment Outcome
  • Weight Gain / drug effects


  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Antagonists
  • Neurotransmitter Agents
  • Receptors, Presynaptic
  • Mianserin
  • Mirtazapine