Migraine Headache Recurrence: Relationship to Clinical, Pharmacological, and Pharmacokinetic Properties of Triptans

Background and Objectives.—Triptan use is associated with headache recurrence, and this has been cited as an important reason for patient dissatisfaction with the treatment. The mechanism by which recurrence occurs is not clear, and the incidence of recurrence varies with the triptan used. In order to explore the pharmacological and physiological interaction of triptans and migraine headache recurrence further, some specific clinical, pharmacological, and pharmacokinetic factors that might influence migraine recurrence were evaluated in a review of the major efficacy data for the drugs in the triptan class. These factors were 5‐HT 1B and 5‐HT 1D receptor activities, the pharmacokinetic elimination half‐life of each triptan, and the clinical efficacy of each compound, determined by the proportion of patients with headache relief and the therapeutic gain over placebo. Methods.—Clinical data were derived from 31 triptan, placebo‐controlled, major efficacy studies used in a previous meta‐analysis. The mean recurrence rate, mean headache response, and therapeutic gain were calculated using the results from the individual clinical studies. Mean headache response and therapeutic gain were calculated at the time point used to define recurrence in each study. Data for binding affinity and potency were taken from a direct‐comparison in vitro pharmacology study, and the elimination half‐life quoted in the data sheet for each triptan was used. Rank correlation with recurrence rate was performed for each of the test parameters. Results.—Mean headache recurrence rates ranged from 17% for frovatriptan 2.5 mg to 40% for rizatriptan. Elimination half‐life and recurrence were inversely correlated ( r = −1.0, P = .0016). There was also a significant inverse correlation between 5‐HT 1B receptor potency and recurrence ( r = −0.68, P = .034), but 5‐HT 1D receptor potency was not correlated with recurrence ( r = −0.20, P = .54). In addition, the binding affinities for the 5‐HT 1B and 5‐HT 1D receptors were not correlated to headache recurrence. Importantly, it also was demonstrated that initial clinical efficacy was not correlated to headache recurrence. The correlation coefficient for headache response was 0.18 ( P = .53) and for therapeutic gain, −0.11 ( P = .71). Conclusion.—The incidence of migraine headache recurrence varies between drugs in the triptan class. Migraine recurrence does not appear to be related to initial clinical efficacy, but is influenced by the pharmacological and pharmacokinetic properties of the individual triptans. The triptans with longer half‐lives and greater 5‐HT 1B receptor potency had the lowest rates of headache recurrence.