Selective Serotonin Re-uptake Inhibitors (SSRIs) for preventing migraine and tension-type headaches

Lorenzo Moja, Cristina Cusi, Roberto Sterzi, Claudio Canepari

Research output: Contribution to journalArticlepeer-review


Background: Headache is a common medical problem. In view of recent discoveries about the role of serotonin in pain mechanisms, selective serotonin re-uptake inhibitors (SSRIs) have been evaluated for the prevention of migraine and tension-type headaches (TTH). Objectives: To evaluate the efficacy and tolerability of SSRIs for preventing migraine and TTH. Search strategy: We searchedMEDLINE (1966-January 2004), EMBASE (1994-May 2003), the Cochrane Central Register of Controlled Trials (Issue 4, 2003), and reference lists of retrieved articles. Headache Quarterly was hand searched from 1990 to 2003. Selection criteria: We included randomised controlled trials comparing SSRIs with any type of control intervention in patients of either sex, over 18 years of age, with migraine or TTH. Data collection and analysis: Two authors independently extracted data (headache frequency, index, severity, and duration; use of symptomatic/analgesic medication; days off work; quality of life; mood improvement; cost-effectiveness; and adverse events) and assessed the methodological quality of trials. Main results: Thirteen studies utilizing five SSRIs met the inclusion criteria (636 participants). Most of the included studies had methodological and/or reporting shortcomings; follow up rarely extended beyond 3 months. After 2 months SSRIs did not significantly lower headache index scores in patients with migraine when compared to placebo (SMD - 0.14; 95% CI -0.57 to 0.30). Patients with chronic TTH treated with an SSRI had a significantly higher analgesic intake of 5 more doses per month when compared to patients treated with a tricyclic antidepressant (WMD 4.98; 95% CI 1.12 to 8.84). Tricyclics also significantly reduced headache duration by 1.26 hours per day (WMD 1.26; 95% CI 0.06 to 2.45) and marginally reduced headache indexes (SMD 0.42; 95% CI 0.00 to 0.85) when compared to SSRIs in patients with chronic TTH. When the data on adverse events were considered without regard to headache diagnostic subgroups, there were no significant differences between SSRIs and placebo for withdrawals due to adverse events (Peto OR 1.02; 95% CI 0.31 to 3.34). For minor adverse events, SSRIs were generally more tolerable than tricyclics (OR 0.34; 95% CI 0.13 to 0.92). However, there were no differences in the number of patients withdrawing due to any reason in the SSRI and tricyclic groups (OR 1.01; 95% CI 0.56 to 1.80). Authors' conclusions: Over 2 months of treatment, SSRIs are no more efficacious than placebo in patients with migraine. In patients with chronic TTH, SSRIs are less efficacious than tricyclic antidepressants. In comparison with SSRIs, the burden of adverse events in patients receiving tricyclics was greater. These results are based on short-term trials and may not generalise to longer-term treatmen.

Original languageEnglish
Article numberCD002919
JournalThe Cochrane database of systematic reviews
Issue number4
Publication statusPublished - 2009


  • Humans
  • Migraine disorders [*drug therapy]
  • Randomized controlled trials as topic
  • Serotonin uptake inhibitors [*therapeutic use]
  • Tension-type headache [*drug therapy]

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology (medical)


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