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Systematic review
Tricyclic antidepressants reduce frequency of tension-type and migraine headaches compared with placebo, and intensity of headaches compared with SSRIs, but cause greater adverse effects
  1. Paul D Molyneux
  1. West Suffolk Hospital NHS Trust and Addenbrookes Hospital, Cambridge, UK
  1. Correspondence to Paul D Molyneux
    West Suffolk Hospital NHS Trust, Hardwick Lane, Bury St Edmunds, Suffolk IP29 4HP, UK; paul.molyneux{at}

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Of the primary headache disorders, tension-type headache (TTH) and migraine account for the majority, with prevalence estimates for migraine between 8.4% and 18% and TTH between 16% and 30% of the population. The socioeconomic burden of headache is huge, with an estimated annual societal cost in the USA of $16.6 billion. A previous smaller meta-analysis1 suggested a beneficial effect of tricyclic antidepressants over placebo for both TTH and migraine. This larger systemic review and meta-analysis aimed to extend previous findings across a larger number of studies, including comparison of tricyclics against selective serotonin reuptake inhibitors (SSRIs).


A meta-analysis using the PRISMA method of reporting was undertaken by searching multiple databases up to early 2010. Inclusion criteria included published, randomised clinical trials evaluating the efficacy of tricyclics for both TTH and migraine in adults. Tricyclics were required to be used as a single …

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  • Competing interests PDM has received support from Merck Serono, Novartis and Bayer Schering to attend conferences.