24 Chapter 1 Preventive treatment In accordance with (inter)national guidelines, preventive treatment is indicated for patients with at least two attacks or at least four migraine days per month. Candesartan and beta-blockers are often used as first choice although the latter might be less effective in women.52 Other preventive medications include topiramate, valproic acid, amitriptyline, flunarizine. For migraine with aura, there is a preference for antiepileptic drugs (lamotrigine, valproic acid, topiramate).53 For women of childbearing age using antiepileptic drugs may be difficult and highly effective contraception is needed due to the risk of teratogenicity. There is no information on the potential differences in effectiveness of these treatments between perimenstrual and non-perimenstrual attacks. In recent years, monoclonal antibodies targeting CGRP (fremanezumab, galcanezumab, eptinezumab) or the CGRP receptor (erenumab) have become available as preventive treatments for migraine. These anti-CGRP monoclonal antibodies are equally effective in reducing perimenstrual attacks as they are for non-perimenstrual attacks.11 Unfortunately, no data has emerged from the clinical trials that distinguishes between men and women, but data from the Food and Drug Administration indicate that anti-CGRP monoclonal antibodies and gepants are effective in both male and female patients with episodic migraine, though potential sex differences in efficacy remain unclear.54 In patients with chronic migraine, anti-CGRP monoclonal antibodies have been found to be similarly effective in both men and women.54 Anti-CGRP agents, besides their beneficial effect on migraine, may potentially alleviate vasomotor symptoms (VMS) as CGRP is implicated in neural regulation affecting vasodilation and cholinergic sweating during hot flushes, and elevated CGRP concentrations have been observed during VMS.55 While mouse studies suggest that blocking CGRP could alleviate VMS, clinical studies are required to validate these findings.56 Short-term prophylaxis for perimenstrual attacks For women with menstrual migraine short-term prophylaxis with acute medication such as NSAIDs or the long acting frovatriptan is often prescribed. This is started 1-2 days before the expected menstruation for a total of 5-7 days. However, the menstrual cycle must be regular or predictable for this to be effective. Besides, with this approach, women often report postponed attacks.57 Additionally, the risk of medication overuse increases with prolonged use of triptans or ditans, especially if migraine attacks also occur outside of menstruation.9 Gepants might offer a revolutionary change in the prevention of these perimenstrual attacks, as they do not seem to have a risk of medication overuse. Given the effectiveness of anti-CGRP monoclonal antibodies in preventing perimenstrual attacks, gepants are likely to be similarly effective.11
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