Tricyclic and Tetracyclic Antidepressants for the Prevention of Frequent Episodic or Chronic Tension-Type Headache in Adults: A Systematic Review and Meta-Analysis

Tension-type headaches are a common source of pain and suffering. Our purpose was to assess the efficacy of tricyclic (TCA) and tetracyclic antidepressants in the prophylactic treatment of tension-type headache. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the ISI Web of Science, and clinical trial registries through 11 March 2017 for randomized controlled studies of TCA or tetracyclic antidepressants in the prevention of tension-type headache in adults. Data were pooled using a random effects approach. Among 22 randomized controlled trials, eight included a placebo comparison and 19 compared at least two active treatments. Eight studies compared TCAs to placebo, four compared TCAs to selective serotonin reuptake inhibitors (SSRIs), and two trials compared TCAs to behavioral therapies. Two trials compared tetracyclics to placebo. Single trials compared TCAs to tetracyclics, buspirone, spinal manipulation, transcutaneous electrical stimulation, massage, and intra-oral orthotics. High-quality evidence suggests that TCAs were superior to placebo in reducing headache frequency (weighted mean differences (WMD): -4.8 headaches/month, 95% CI: -6.63 to -2.95) and number of analgesic medications consumed (WMD: -21.0 doses/month, 95% CI: -38.2 to -3.8). TCAs were more effective than SSRIs. Low-quality studies suggest that TCAs are superior to buspirone, but equivalent to behavioral therapy, spinal manipulation, intra-oral orthotics, and massage. Tetracyclics were no better than placebo for chronic tension-type headache. Tricyclic antidepressants are modestly effective in reducing chronic tension-type headache and are superior to buspirone. In limited studies, tetracyclics appear to be ineffective in the prophylactic treatment of chronic tension-type headache.