Tricyclic antidepressants and headaches: Systematic review and meta-analysis

Jeffrey L. Jackson, William Shimeall, Laura Sessums, Kent J. DeZee, Dorothy Becher, Margretta Diemer, Elizabeth Berbano, Patrick G. O'Malley

Research output: Contribution to journalReview articlepeer-review

148 Scopus citations


Objective: To evaluate the efficacy and relative adverse effects of tricyclic antidepressants in the treatment of migraine, tension-type, and mixed headaches. Design: Meta-analysis. Data sources: Medline, Embase, the Cochrane Trials Registry, and PsycLIT. Studies reviewed: Randomised trials of adults receiving tricyclics as only treatment for a minimum of four weeks. Data extraction: Frequency of headaches (number of headache attacks for migraine and number of days with headache for tension-type headaches), intensity of headache, and headache index. Results: 37 studies met the inclusion criteria. Tricyclics significantly reduced the number of days with tension-type headache and number of headache attacks from migraine than placebo (average standardised mean difference -1.29, 95% confidence interval -2.18 to -0.39 and -0.70, -0.93 to -0.48) but not compared with selective serotonin reuptake inhibitors (-0.80, -2.63 to 0.02 and -0.20, -0.60 to 0.19). The effect of tricyclics increased with longer duration of treatment (β=-0.11, 95% confidence interval -0.63 to -0.15; P<0.0005). Tricyclics were also more likely to reduce the intensity of headaches by at least 50% than either placebo (tension-type: relative risk 1.41, 95% confidence interval 1.02 to 1.89; migraine: 1.80, 1.24 to 2.62) or selective serotonin reuptake inhibitors (1.73, 1.34 to 2.22 and 1.72, 1.15 to 2.55). Tricyclics were more likely to cause adverse effects than placebo (1.53, 95% confidence interval 1.11 to 2.12) and selective serotonin reuptake inhibitors (2.22, 1.52 to 3.32), including dry mouth (P<0.0005 for both), drowsiness (P<0.0005 for both), and weight gain (P<0.001 for both), but did not increase dropout rates (placebo: 1.22, 0.83 to 1.80, selective serotonin reuptake inhibitors: 1.16, 0.81 to 2.97). Conclusions: Tricyclic antidepressants are effective in preventing migraine and tension-type headaches and are more effective than selective serotonin reuptake inhibitors, although with greater adverse effects. The effectiveness of tricyclics seems to increase over time.

Original languageEnglish
Article numberc5222
Pages (from-to)869
Number of pages1
JournalBMJ (Online)
Issue number7778
StatePublished - 23 Oct 2010
Externally publishedYes


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