Tricyclic antidepressants and headaches: systematic review and meta-analysis.
OBJECTIVE
To evaluate the efficacy and relative adverse effects of tricyclic antidepressants in the treatment of migraine, tension-type, and mixed headaches.


METHODS
Meta-analysis.


METHODS
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.


METHODS
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.
General Medicine Division, Walter Reed Army Medical Center, Washington, DC, USA. Jeffrey.jackson6@va.gov
Jeffrey L
JL
Jackson
William
W
Shimeall
Laura
L
Sessums
Kent J
KJ
Dezee
Dorothy
D
Becher
Margretta
M
Diemer
Elizabeth
E
Berbano
Patrick G
PG
O'Malley
D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D020773:Headache Disorders / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000929:Antidepressive Agents, Tricyclic; D017367:Selective Serotonin Reuptake Inhibitors