Treatment of chronic headache with antidepressants: a meta-analysis

Am J Med. 2001 Jul;111(1):54-63. doi: 10.1016/s0002-9343(01)00762-8.


Background: Although antidepressants are often used for preventing chronic headache, their effectiveness is uncertain.

Methods: We performed a meta-analysis of English-language, randomized placebo-controlled trials of antidepressants as prophylaxis for chronic headache.

Results: Thirty-eight trials were included. Because some compared more than one drug with placebo, 44 study arms were combined using a random effects model. Twenty-five studies focused on migraines, 12 on tension headaches, and 1 on both. Nineteen used tricyclic antidepressants, 18 serotonin antagonists, and 7 selective serotonin reuptake inhibitors. Patients receiving antidepressants were twice as likely to report headache improvement (rate ratio [RR]: 2.0; 95% confidence interval [CI]: 1.6 to 2.4). Because 31% (95% CI: 23% to 40%) more treated patients improved than those receiving placebo, clinicians would need to treat 3.2 patients for 1 patient to improve. The average amount of improvement (standardized mean difference) was 0.94 (95% CI: 0.65 to 1.2), an effect considered large. Treated patients also consumed less analgesic medication (standardized mean difference, -0.7; 95% CI: -0.5 to -0.94). There were no differences in outcomes among the three classes of agents studied or by the type of headache (migraine vs. tension), quality score, length of treatment, or percentage of patients lost to follow-up. Assessment of depression across studies was insufficient to determine if the effects were independent of depression.

Conclusion: Antidepressants are effective in preventing chronic headaches. Whether this is independent of depression and whether there are differences in efficacy by class of agent needs further study.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / therapeutic use*
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Chronic Disease
  • Headache / drug therapy
  • Headache / prevention & control*
  • Humans
  • Outcome Assessment, Health Care
  • Randomized Controlled Trials as Topic
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin Antagonists / therapeutic use
  • Treatment Outcome


  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors