Page 24 - The clinical aspects and management of chronic migraine Judith Anne Pijpers

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Chapter 1
RCTs studying BTA show similar small effects sizes: In the registration the trials, the therapeutic gain of BTA versus placebo was an additional reduction of 1.8 headache days per month. As the baseline number of headache days was 19.9 the percentage change was only 9%.81 Another important issue in the BTA studies is potential bias by unblinding of participants. As study medication was injected at 31 sites including the forehead, removal of wrinkling in the BTA group would likely cause unblinding versus placebo.84,85 Reports on blinding of participants were not provided in these studies, but in trials using similar designs, 85% of BTA-treated participants correctly guessed their treatment.85,86 Phenomena as placebo and nocebo effect might have increased the difference between BTA and placebo.85,87,88 With these remarks on RCTs at preventatives in chronic migraine and medication overuse, and the beneficial effect of withdrawal therapy in mind, both the Dutch national guidelines89 and international literature10,58 do recommend withdrawal therapy in case of medication overuse.
The small effect sizes of the preventatives studied in chronic migraine patients also stresses the need of effective therapy for these patients, especially the subpopulation who still suffer chronic migraine after withdrawal therapy.
Outline of the thesis
In this thesis, the clinical aspects and management of chronic migraine are investigated in order to enhance treatment of chronic migraine, and ultimately prevent migraine chronification. As described in this introduction, migraine chronification is a multifactorial phenomenon, with numerous related factors. Due to the complexity of the process, and limitations of scientific work in proving causality, it is not always clear which factor occurs first and causes the other. Therefore, it is important to analyse and interpret these factors concurrently, preferably using longitudinal study designs.
This thesis pays attention to risk factors for chronic migraine; depression, anxiety, medication overuse (chapters 2 and 3) and allodynia (chapters 2, 3 and 6), and treatment of chronic migraine by means of withdrawal therapy, botulinum toxin A and care by a specialized headache nurse (chapters 3, 4 and 5), in order to reverse chronic migraine to episodic migraine. Finally, it aims to study predictors of response and enhance insight in pathophysiology