PHILADELPHIA - Adherence to migraine prophylactics drops off sharply within a few months of the initial prescription and falls even farther by 1 year, based on claims data from approximately 8,700 patients.
By 6 months, only 30% of patients were adherent to their preventive medications, defined as taking them as directed at least 80% of the time, Zsolt Hepp, Pharm.D., said at the annual meeting of the American Academy of Neurology. By 12 months, adherence dropped to about 20%; fewer than 1 in 5 patients.
"Adherence rates were alarmingly low," said Dr. Hepp, a researcher for Allergan. "And no matter what class of drugs we looked at, the rates were similar."
Dr. Hepp and his colleagues conducted a retrospective analysis using 2007-2012 claims data from the Truven Health Analytics MarketScan Database. The system contains Medicare, supplemental, and Medicaid claims for more 40 million unique patients per year. Patients, who were at least 18 years old, were diagnosed with chronic migraine, and who initiated an oral migraine prophylactic medication between 2008-2012 were included in the analysis.
Dr. Zsolt Hepp
The initial study group comprised more than 76,000 patients, but exclusion criteria narrowed it to about 8,700, as the researchers tried to pinpoint prescriptions that were solely for migraine. Since most of the 14 medications investigated have different primary indications, the team excluded patients with a diagnosis for that another indication (depression, for example) within a year prior to the migraine diagnosis.
The analysis also included only patients who had full, unlapsed insurance coverage during the year of interest; many in the original cohort were excluded because of such lapses.
The 14 commonly prescribed migraine medications in the study included four recommended by the American Academy of Neurology as first-line preventives.
The drugs examined were antidepressants (nortriptyline and amitriptyline, citalopram, sertraline, fluoxetine, paroxetine, and venlafaxine), beta-blockers (propranolol, metoprolol, atenolol, and nadolol), and anticonvulsants (divalproex, gabapentin, and topiramate).
The majority of patients were women, with a mean age of 40 years. Most (59%) were employed full time. Common comorbidities included nonmigraine headache (54%), cancer (22%), hypertension (18%), depression (18%), sleep disorders (11%), and gastroesophageal reflux disease (11%).
The adherence rates were surprisingly similar across drug classes, Dr. Hepp noted. Overall adherence rates using the Medication Possession Ratio hovered at 28%-29% at 6 months and 19%-21% at 12 months.
When broken down by individual drug, the antidepressants had the highest rates of adherence at 6 months. Venlafaxine and fluoxetine topped the list, with 37% of patients adherent at 6 months. However, by 12 months, adherence had dropped to 28% for venlafaxine and 22% for fluoxetine.
"All of these medications need to be taken at least once daily – and sometimes several times a day – to really maintain their effectiveness," Dr. Hepp noted. "This is the first real-world analysis of the U.S. migraine population, and we feel the results are generalizable to that population."
Unfortunately, he said, a claims database doesn’t give any insight into why patients stop taking their medication. One view came up during the discussion period, however.
"People don’t want to take drugs that make them gain weight or feel stupid," one discussant said bluntly.
Dr. Hepp added that this low adherence was not surprising, in light of research that shows similar problems with other chronic diseases.
A 2009 study examined six different chronic conditions, including hypertension and diabetes, he said. "By far the best adherence rates were for diabetes, and that was only about 60% by 12 months."
Although the claims database revealed nothing about the factors driving the lack of adherence, data from previous studies suggest that side effects and dissatisfaction are likely suspects, Dr. Hepp said. His own previous study on the reasons for discontinuation in clinical trials of three migraine treatments showed that "a significant portion of the discontinued patients decided to stop treatment due to side effects," he said in an interview. I actually have another publication that was a systematic literature review of adherence manuscripts.
"Another study by Blumenfeld et al. 2013 found that top reasons for discontinuation of oral migraine prophyalctics were side effects and treatment satisfaction," he said. "It’s likely that these other studies highlight the very reason(s) why we saw the level of nonadherence in our study," he said. "Our results most certainly call attention to the large gap in the treatment of this highly burdened population, and at the very least this study calls for further research and hopefully the integration of adherence into future clincial trials for migraine prevention tretaments."