Review
Treatment of chronic headache with antidepressants: a meta-analysis1,

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Abstract

BACKGROUND: Although antidepressants are often used for preventing chronic headache, their effectiveness is uncertain.

METHODS: We performed a meta-analysis of English-language, randomized placebo-controlled trials of antidepressants as prophylaxis for chronic headache.

RESULTS: Thirty-eight trials were included. Because some compared more than one drug with placebo, 44 study arms were combined using a random effects model. Twenty-five studies focused on migraines, 12 on tension headaches, and 1 on both. Nineteen used tricyclic antidepressants, 18 serotonin antagonists, and 7 selective serotonin reuptake inhibitors. Patients receiving antidepressants were twice as likely to report headache improvement (rate ratio [RR]: 2.0; 95% confidence interval [CI]: 1.6 to 2.4). Because 31% (95% CI: 23% to 40%) more treated patients improved than those receiving placebo, clinicians would need to treat 3.2 patients for 1 patient to improve. The average amount of improvement (standardized mean difference) was 0.94 (95% CI: 0.65 to 1.2), an effect considered large. Treated patients also consumed less analgesic medication (standardized mean difference, −0.7; 95% CI: −0.5 to −0.94). There were no differences in outcomes among the three classes of agents studied or by the type of headache (migraine vs. tension), quality score, length of treatment, or percentage of patients lost to follow-up. Assessment of depression across studies was insufficient to determine if the effects were independent of depression.

CONCLUSION: Antidepressants are effective in preventing chronic headaches. Whether this is independent of depression and whether there are differences in efficacy by class of agent needs further study.

Section snippets

Material and methods

We searched MEDLINE (1966–December 1998), PsycLIT (1974–December 1998), and EMBASE (1974–December 1998) using the following text and key words (all languages, limited to “human”): antidepressive agents, serotonin uptake inhibitors, monoamine oxidase inhibitors, tricyclic, amoxapine, clomipramine, trimipramine, desipramine, doxepin, imipramine, maprotiline, amitriptyline, nortriptyline, protriptyline, trazodone, nefazodone, fluoxetine, fluvoxamine, paroxetine, sertraline, femoxetine,

Study characteristics

The literature search identified 41 randomized, placebo-controlled trials of antidepressant use in headache. Data from three of these studies could not be pooled because the articles did not report sample size or variance, which are necessary for combining data 15, 16, 17, 18. The remaining 38 studies (Table 1; references 6, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55) had moderate quality

Discussion

Meta-analysis of the 38 published randomized controlled trials suggests that antidepressants are effective in reducing chronic headache pain. Patients receiving antidepressants were twice as likely to improve, with about 3 patients needing treatment to improve 1 patient’s symptoms. Patients had a mean reduction in headache burden of nearly 1 SD unit and a reduced analgesic consumption of 0.7 SD units. A difference of 0.8 SD units is commonly considered to be a large treatment effect (58).

Acknowledgements

The authors wish to acknowledge the assistance of Robert Mohrman in the systematic search of the literature.

References (67)

  • W.F Stewart et al.

    Prevalence of migraine headache in the United States

    JAMA

    (1992)
  • X.H Hu et al.

    Burden of migraine in the United States

    Arch Intern Med

    (1999)
  • Adams RD, Victor M, Ropper AH. Principles of Neurology. 6th ed. New York: McGraw-Hill;...
  • A.M Rapaport

    Recurrent migrainecost-effective care

    Neurology

    (1994)
  • N.T Mathew

    Transformation of episodic migraine into daily headacheanalysis of factors

    Headache

    (1982)
  • M Egger et al.

    Bias in meta-analysis detected by a simple, graphical test

    BMJ

    (1997)
  • R.F Galbraith

    A note on graphical presentation of estimated odds ratios from several clinical trials

    Stat Med

    (1988)
  • Ryan RE. Double-blind crossover comparison of BC105, methylsergide and placebo in the prophylaxis of migraine headache....
  • R.S Havanka-Kannianinen et al.

    Efficacy of nimodipine in comparison with pizotifen in the prophylaxis of migraine

    Cephalagia

    (1987)
  • B.J.J Ansink et al.

    Ritanserin is not effective in tension headache

    Headache

    (1992)
  • J.D Gomersall et al.

    Amitriptyline in migraine prophylaxischanges in pattern of attacks during a controlled clinical trial

    J Neurol Neurosurg Psychiatry

    (1973)
  • N Martucci et al.

    Migraine and the noradrenergic control of vasomotricitya study with alpha-2 stimulant and alpha-2 blocker drugs

    Headache

    (1985)
  • R.E Ryan

    BC-105 a new preparation for the interval treatment of migraine—a double blind evaluation compared with placebo

    Headache

    (1971)
  • J.F Noone

    Clomipramine in the prevention of migraine

    J Int Med Res

    (1980)
  • I Zeeberg et al.

    Femoxetine in the prophylaxis of migraine—a randomized comparison with placebo

    Acta Neurol Scand

    (1981)
  • H.D Langohr et al.

    Clomipramine and metoprolol in migraine prophylaxis—a double-blind crossover study

    Headache

    (1985)
  • A Okasha et al.

    A double-blind trial for the clinical management of psychogenic headache

    Brit J Psychiatry

    (1973)
  • T.J Morland et al.

    Doxepin in the prophylactic treatment of mixed “vascular” and tension headache

    Headache

    (1979)
  • P Kangasniemi

    Placebo, 1-isopropylnoradrenochroe-5-monosemicarbasano, and pizotifen in migraine prophylaxis

    Headache

    (1979)
  • O Sjaastad et al.

    Appraisal of BC-105 in migraine prophylaxis

    Acta Neurol Scandinav

    (1969)
  • G.P Arthur et al.

    The treatment of migraine with BC-105 (pizotifen)a double-blind trial

    NZ Med J

    (1971)
  • R.C Hughes et al.

    BC-105 in the prophylaxis of migraine

    Curr Ther Res

    (1971)
  • S Diamond et al.

    Chronic tension headache—treated with amitriptyline—a double-blind study

    Headache

    (1971)
  • Cited by (0)

    Supported by a grant from the MacArthur Foundation Initiative on Depression in Primary Care (PGO).

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    Disclaimer: The views in this article reflect those of the authors and are not intended to represent in any way those of the U.S. Army or the Department of Defense.

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