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.
Jackson
Jeffrey L
JL
General Medicine Division, Walter Reed Army Medical Center, Washington, DC, USA. Jeffrey.jackson6@va.gov
Shimeall
William
W
Sessums
Laura
L
Dezee
Kent J
KJ
Becher
Dorothy
D
Diemer
Margretta
M
Berbano
Elizabeth
E
O'Malley
Patrick G
PG
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