Tricyclic antidepressants and headaches: systematic review and meta-analysis

Abstract

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.

Fig 1 Flow of articles through study

Fig 2 Effect of tricyclic antidepressants on burden of headache for tension-type and migraine headaches compared with placebo. Trials of mixed and migraine headaches are combined

Fig 3 Effect of tricyclic antidepressants compared with placebo over time. SMD=standardised mean difference

Fig 4 Likelihood of experiencing at least 50% reduction in tension-type and migraine headaches compared with placebo. Trials of mixed and migraine headaches are combined

Fig 5 Likelihood of adverse effects between tricyclic antidepressants and placebo

Fig 6 Comparison of effectiveness of tricyclic antidepressants with selective serotonin reuptake inhibitors for tension-type and migraine headaches. Trials of mixed and migraine headaches are combined. SSRI=selective serotonin reuptake inhibitor

Fig 7 Likelihood of experiencing 50% clinical improvement with tricyclics compared with selective serotonin reuptake inhibitors. Trials of mixed and migraine headaches are combined. SSRI=selective serotonin reuptake inhibitor