21 General introduction 1 intake is thus important. Also, a triptan or ditan should be taken at the beginning of the headache phase (Figure 5a), as they have no effect on CSD. Women more often experience side effects from triptans than men.20 This can be explained by a higher maximum plasma concentration compared to men. The initial response is similar in men and women, yet despite higher plasma concentrations women have an increased risk of recurrences.20 In cases of side effects, lowering the dosage for women should therefore be avoided, as it may further increase the likelihood of recurrences. Instead, opting to switch to another triptan or other migraine specific acute treatment is advisable. Regrettably, in practice, it remains common for clinicians to prescribe triptans in too low doses. However, this practice exacerbates recurrences, increases medication usage, and consequently, increases the risk of chronification. A novel class of acute medication are the gepants, which are small molecular CGRP receptor antagonists. In clinical trials, the efficacy of gepants is comparable to that of triptans.47 Rimegepant can be used as both acute and preventive treatment, challenging the traditional view of the division between acute and preventive treatments.47 Medication overuse headache Women are more prone to develop medication overuse headache (MOH) due to their longer attack duration and thereby increased triptan or ditan intake.8, 10, 20 MOH is defined as the use of triptans, ditans, opioids, or in combinations with analgesics, on ten or more days per month, or the use of simple analgesics on 15 or more days per month, for at least three months.1 The pathophysiological mechanisms of MOH include changes in descending pain modulation, central sensitization with increased responsiveness and excitability of neurons, and biobehavioural factors.46 Both triptans and lasmiditan can induce hypersensitivity and increase the risk of progression to MOH in patients with an underlying headache condition when used excessively.48 For lasmiditan, this has so far only been demonstrated in preclinical models.49 Importantly, gepants do not seem to induce MOH-like phenotypes in mice.48, 50 Therefore, they have the potential for longer treatment during the perimenstrual window without the risk of MOH and chronification of attacks. Treatment of recurrences of (perimenstrual) attacks Recurrences often occur during perimenstrual attacks and treatment should be adjusted (Figure 5b). The first step would be to treat (perimenstrual) attacks with adequate dose of medication. If a woman is using sumatriptan 50 mg or lasmiditan
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