Selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine or tension-type headaches

Moja L, Cusi C, Sterzi R, Canepari C

Published Online:

October 7, 2009

Migraine and tension-type headaches are common and can interfere significantly with social functioning, daily activities, and work. People with very frequent or severe headaches may benefit from preventive drug therapy. Selective serotonin re-uptake inhibitors (SSRIs) block the passage of serotonin, a neurotransmitter, in brain cells. They are typically used to treat depression. In view of research suggesting that serotonin may play a role in the genesis of headache pain, SSRIs have also been tested for their potential benefit in preventing headaches. This review identified 13 trials (636 patients) lasting 2 to 3 months. The trials were small, and only a few were of high quality. Results suggest that SSRIs are no better than placebo (sugar pill) for preventing migraine or tension-type headaches. Compared with other active treatments, specifically tricyclic antidepressants, SSRIs were no better for migraine and were less effective for tension-type headache. Effects beyond 3 months are unknown. Minor side effects were no more common with SSRIs than with placebo and were less common with SSRIs than with tricyclics. The numbers of people who stopped taking tricyclics and SSRIs due to side effects were approximately equal.

Abstract (click to read)

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 searched MEDLINE (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 treatment.

This record should be cited as:

Moja L, Cusi C, Sterzi R, Canepari C. Selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine and tension-type headaches. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD002919. DOI: 10.1002/14651858.CD002919.pub2

Assessed as up to date:

January 31, 2004

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Primary Review Group:

Pain, Palliative and Supportive Care Group

Health topics:

Neurology > Headache & migraine > Prevention

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine or tension-type headaches

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