Page 71 - The clinical aspects and management of chronic migraine Judith Anne Pijpers

Withdrawal and botulinum toxin A: a double blind RCT
Treatments and masking
In accordance to our national guidelines33 and other withdrawal studies,6,8,11,12 participants were instructed to withdraw abruptly from all acute headache medications and caffeine in an outpatient setting for 12 weeks. Prophylactic treatment was tapered off and rescue medication to treat headaches of any kind was not allowed. Patients were explained what to expect after withdrawal, including the likely occurrence of sometimes severe withdrawal symptoms, and were informed about the possible practical, social and professional consequences.
BTA was administered at 31 predefined injection sites (5 units per injection; in total 155 units), in accordance with published protocols.23 Placebo was administered at the same 31 injection sites. However, while the 24 injections outside the forehead region contained saline, the seven injections in the forehead contained low dose BTA (2.5 units per injection site; 17.5 units in total). Participants were explained that change in facial expression was not indicative of any particular treatment. Active and placebo treatment were indistinguishable. Patients and investigators were blinded for treatment.
Outcomes
There is no universally agreed primary endpoint for trials in chronic migraine. The differences, however, between the various recommended34,35 and used endpoints36–40 are in fact only marginal. We choose as primary outcome the percentage change in 4-weekly headache days from baseline to the last four weeks of double-blind treatment (weeks 9-12). As chronic migraine patients have a high headache frequency at baseline, percentage change in headache days is considered a more meaningful endpoint than absolute change. Percentage change was calculated as change in number of headache days per 4 weeks, divided by the number of baseline headache days. A headache day was any calendar day on which a migraine or non-migraine headache of any duration was reported. We did not include a minimal duration of 4 hours (as used in some trials), as most of our participants would usually use medication within 4 hours after headache onset. For the same reason we decided not to specify that headache had to have a moderate or severe peak intensity.
Secondary outcomes were assessed 12, 24, 36 and 48 weeks after therapy onset. The main secondary outcome was change in quality of life (SF-36). Additional
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