Tricyclic antidepressants for migraine and tension-type headaches

Tricyclic antidepressants have a long history in the treatment of headache. In 1964 Lance and Curran reported a better response to amitriptyline (30-75 mg/day) in chronic tension headache (n=280) compared with 11 other commonly used drugs (such as benzodiazepines, vasodilators, and sedatives). They also reported a placebo controlled crossover trial of 27 patients that showed clinically significant improvements (≥50% reduction) in headaches in 55% of patients taking amitriptyline, but only 11% of those taking placebo. When the results for amitriptyline were aggregated across the two studies, the effect of amitriptyline became more pronounced over time, was independent of the presence of depression, was evident in patients with continuous as well as episodic headaches, and was most pronounced in older (≥60 year of age) patients. A decade passed before similar positive findings were reported for migraine. With replication of these findings tricyclic antidepressants, particularly amitriptyline, have been recommended in textbooks for at least 35 years. With the advent of formal treatment guidelines for headache, tricyclics also have been recommended in clinical guidelines for the treatment of tension-type headache and migraine. The current meta-analysis updates the evidence base for tricyclic antidepressants in the treatment of migraine and tension headache.Results from the 37 trials of tricyclic antidepressants are analysed; the 20 placebo controlled trials primarily evaluate amitriptyline (14 trials) or clomipramine (four trials). The meta-analysis largely confirms Lance and Curran’s original observations. Across trials, low dose tricyclic antidepressants (mean amitriptyline dose 80 mg/day) reduced headache by at least 50% compared with placebo (tension: relative risk 1.41, 95% confidence interval 1.02 to 1.89; migraine: 1.80, 1.24 to 2.62). The proportion of people who stopped treatment did not differ significantly between people taking tricyclic antidepressants or placebo. Treatment effects increased over time. Other preventive drugs (topiramate or β blockers) showed no advantage over tricyclic antidepressants. Tricyclic