Using a large clinical migraine cohort (n = 1913) including information on treatment response, we found a highly significant association between the number of purchases of triptans and positive treatment response, defined as having at least 50% reduction in symptoms within two hours of treatment start. We showed that the sensitivity was high (> 80%) for prediction of positive response to triptans and that the sensitivity was above 70% if the patients had more than ten purchases. We did not find evidence for an association between treatment response and purchases of non-migraine specific analgesics or ergotamines. We did not expect to observe an association, as non-migraine specific analgesics can be bought over-the-counter and are used for many other indications putatively introducing substantial statistical noise.
It is expected that migraine patients who purchase triptans more than once only do so if they experience a positive response. However, we observed an expected increase in sensitivity with number of purchases, although ten purchases of triptans were needed to reach 70% sensitivity. Since this is a retrospective study, this may be a consequence of recall bias. In addition, the positive response criterion of having 50% reduction of symptoms within two hours might exclude patients with marginally less or slower effect of triptans. An interesting future study would be to assess the individual migraine drugs. We demonstrated that analysing single drugs necessitates fewer purchases of the drug to gain the 80% specificity. However, a larger sample size is needed and, although more labour intensive, prospective studies may be needed. However, a key future goal is to compare treatment outcome with genetics, which requires that all participants must be genotyped. Here, thousands of patients are usually required to gain enough statistical power to assess common variants. Thus, a prospective migraine diary-based study seems less feasible.
We found a highly significant association between purchases of prophylactic drugs and a positive treatment response, defined as a more than a 50% reduction of their migraine attacks, from using angiotensin II antagonists, beta-blockers, or antiepileptics. We found a high sensitivity (> 80%) predicting positive treatment response from the number of purchases, and a specificity above 70% after at least three or four purchases depending on the drug. Whereas triptans are specific migraine drugs, the prophylactic drugs are not. As a result, the prediction model for prophylactic drugs necessitates knowledge of the prescription indication. Some drugs may be used to treat a multitude of conditions (e.g. epilepsy, arterial hypertension). Hence, we repeated the analysis excluding patients with comorbid disease. The association remained significant, although we observed a significant drop in the average number of purchases of antiepileptics.
Our study design included general triptan use and response, thus we were unable to test for an association between number of different triptans purchased and patients reporting no treatment effect. Future studies including more complex analysis of the types of triptans, patterns of medication exposures, etc., may aid in the characterization of migraine patient groups.
Precision medicine may offer new strategies to treat migraine, and access to existing large cohorts and pharmacy databases may help reach the required larger sample sizes. Based on the current results we recommend using ten purchases for triptans and three or four purchases for prophylactics. We anticipate that using fewer purchases, e.g. three triptans, may be sufficient; however, this should be evaluated in future studies. Notably, more than 75% of the triptan users have purchased triptans at least ten times, and 55–63% of the prophylactic users have at least three or four purchases. Additional factors may also influence treatment response, such as the use of other drugs [13,14,15], i.e. polypharmacy, as well as presence of co-morbid disorders. Here, it is possible that temporal aspect when additional drugs are prescribed, as a prescription could reflect treatment of adverse-effects. Further, it is easy to imagine that migraine patients with co-morbid depression may experience a better response to anti-depressants [16]. Most likely, genetic factors may also condition the treatment response, as seen for lithium and anti-psychotics [17,18,19], although studies on migraine drugs so far have been inconclusive or lack replication [13, 15].