A Cochrane review included 8 studies with a total of 412 participants with chronic forms of tension-type headache. A total of 68% of patients were women. The studies evaluated 5 SSRIs (citalopram, sertraline, fluoxetine, paroxetine, fluvoxamine) and one SNRI (venlafaxine). Six studies compared SSRIs to other antidepressants (amitriptyline, desipramine, sulpiride, mianserin). Follow-up ranged between 2 and 4 months. Six studies explored the effect of SSRIs or SNRIs on tension-type headache frequency, the primary endpoint. At 8 weeks of follow-up, there was no difference when compared to placebo (MD -0.96, 95% CI -3.95 to 2.03; 2 studies, n = 127) or amitriptyline (MD 0.76, 95% CI -2.05 to 3.57; 2 studies, n = 152). SSRIs reduce the symptomatic/analgesic medication use for acute headache attacks compared to placebo (MD -1.87, 95% CI -2.09 to -1.65; 2 studies, n = 118). However, amitriptyline appeared to reduce the intake of analgesic more efficiently than SSRIs (MD 4.98, 95% CI 1.12 to 8.84). There were no differences compared to placebo or other antidepressants in headache duration and intensity. SSRIs or SNRI were generally more tolerable than tricyclics. However, the two groups did not differ in terms of number of participants who withdrew due to adverse events or for other reasons (OR 1.04; 95% CI 0.41 to 2.60; and OR 1.55, 95% CI 0.71 to 3.38; 4 studies, n = 257). There were no studies comparing SSRIs or SNRIs with pharmacological treatments other than antidepressants (e.g. botulinum toxin) or non-drug therapies (e.g. psycho-behavioural treatments, manual therapy, acupuncture).
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment), inconsistency (heterogeneity in treatments and outcomes) and indirectness (short follow-up).
Another Cochrane review included 13 studies with a total of 636 subjects. The trials compared SSRIs with any type of other antidepressants in patients with migraine or TTH.
After 2 months, selective serotonin re-uptake inhibitors (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 tension-type headaches (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).
Comment: The quality of evidence is downgraded by study quality (inadequate allocation concealment), inconsistency (heterogeneity in comparisons and outcomes) and indirectness (short follow-up).
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