Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Oct 20;341:c5222.
doi: 10.1136/bmj.c5222.

Tricyclic Antidepressants and Headaches: Systematic Review and Meta-Analysis

Affiliations
Free PMC article
Review

Tricyclic Antidepressants and Headaches: Systematic Review and Meta-Analysis

Jeffrey L Jackson et al. BMJ. .
Free PMC article

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.

Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at (www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that (1) they have no relationships with companies that might have an interest in the submitted work; (2) their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and (3) no authors have any non-financial interests that may be relevant to the submitted work.

Figures

None
Fig 1 Flow of articles through study
None
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
None
Fig 3 Effect of tricyclic antidepressants compared with placebo over time. SMD=standardised mean difference
None
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
None
Fig 5 Likelihood of adverse effects between tricyclic antidepressants and placebo
None
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
None
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

Comment in

Similar articles

See all similar articles

Cited by 34 articles

See all "Cited by" articles

References

    1. Wang SJ. Epidemiology of migraine and other types of headache in Asia. Curr Neurol Neurosci Rep 2003;3:104-8. - PubMed
    1. Rasmussen BK. Epidemiology of headache. Cephalalgia 2001;21:774-7. - PubMed
    1. Hu XH, Markson LE, Lipton RB, Stewart WF, Berger ML. Burden of migraine in the United States: disability and economic costs. Arch Intern Med 1999;159:813-8. - PubMed
    1. Lance JW, Curan DA. Treatment of chronic tension headache. Lancet 1964;1:1236-9. - PubMed
    1. Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2007;68:343-9. - PubMed

MeSH terms

Substances

Feedback