Page 67 - The clinical aspects and management of chronic migraine Judith Anne Pijpers
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Withdrawal and botulinum toxin A: a double blind RCT
Introduction
Chronic migraine is a highly disabling and difficult to treat form of migraine,1–3 affecting nearly 2% of the general population.1,2 It is defined by occurrence of headaches on ≥ 15 days per month for > 3 months, of which ≥ 8 days fulfil migraine criteria.1–3 The majority of patients overuse acute headache medications including analgesics , triptans, and opioids.1,2 “Medication overuse” is a major risk factor for transformation from episodic (< 15 headache days) to chronic migraine and an important factor in maintaining and aggravating chronification.1–3 Acute withdrawal may be a cost-effective therapy to reduce headache frequency, improve quality of life, halt medication overuse-induced adverse events, and prevent systemic toxicity.1,4–13 It might also improve efficacy of migraine prophylactics.1,7,14 Unfortunately, acute withdrawal is frequently hampered by acute withdrawal symptoms, which may considerably disrupt patient’s daily life, comfort, and mental state.15,16 Because of these withdrawal symptoms, many physicians are reluctant to recommend withdrawal, despite the potential advantages.7,16,17
Recently, botulinum toxin A (BTA)18 has emerged as therapy for chronic migraine.16,19–25 There is, however, controversy regarding its efficacy, in particular in patients with medication overuse.1,17,26 In the registration trials, the therapeutic gain of BTA versus placebo was only modest, with an additional reduction of 1.8 headache days from 19.9 at baseline (percentage change: 9%).23 Moreover, unblinding might have influenced efficacy. Study medication was injected at 31 sites including the forehead, that will remove wrinkling and likely cause unblinding versus placebo.26,27 In trials using similar designs, 85% of BTA-treated participants correctly guessed their treatment.27,28
A second important issue is that approximately 65% of the participants in these studies were overusing medication, and might have benefitted from withdrawal.20–24 Direct, double-blind comparison of withdrawal versus BTA is technically hardly feasible. Placebo-matching for the various types and combinations of overused medications is virtually impossible, as well as controlling for the psychological effects of withdrawal. We compared acute withdrawal plus BTA administered according to standard protocols20–24 versus acute withdrawal plus placebo in a double-blind, randomised clinical trial in
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