Combination of low-dose mirtazapine and ibuprofen for prophylaxis of chronic tension-type headache.
Chronic headaches are difficult to treat and represent the biggest challenge in headache centres. Mirtazapine has a prophylactic and ibuprofen an acute effect in tension-type headache. Combination therapy may increase efficacy and lower side effects. We aimed to evaluate the prophylactic effect of a combination of low-dose mirtazapine and ibuprofen in chronic tension-type headache. Ninety-three patients were included in the double-blind, placebo-controlled, parallel trial. Following a 4-week run-in period they were randomized to four groups for treatment with a combination of mirtazapine 4.5 mg and ibuprofen 400 mg, placebo, mirtazapine 4.5 mg or ibuprofen 400 mg daily for 8 weeks. Eighty-four patients completed the study. The primary efficacy parameter, change in area under the headache curve from run-in to the last 4 weeks of treatment, did not differ between combination therapy (190) and placebo (219), P = 0.85. Explanatory analyses revealed worsening of headache already in the third week of treatment with ibuprofen alone. In conclusion, the combination of low-dose mirtazapine and ibuprofen is not effective for the treatment of chronic tension-type headache. Moreover, the study suggests that daily intake of ibuprofen worsens headache already after few weeks in chronic tension-type headache.
Bendtsen
L
L
Department of Neurology, Danish Headache Center, Glostrup Hospital, University of Copenhagen, Glostrup, Copenhagen, Denmark. bendtsen@dadlnet.dk
Buchgreitz
L
L
Ashina
S
S
Jensen
R
R
D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D018781:Tension-Type Headache / Q000517:prevention & control*; D017211:Treatment Failure
D000317:Adrenergic alpha-Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008803:Mianserin; D000078785:Mirtazapine; D007052:Ibuprofen