Comparative Effectiveness of Migraine Preventive Medications: The APT Comparison Study

Inclusion Criteria:

• Adults, 18-70 years of age at the time of enrollment

• Migraine with aura, migraine without aura, and/or chronic migraine; according toICHD-3 diagnostic criteria. (Those with daily or continuous headaches are notexcluded.)

• Migraine onset prior to 50 years of age

• Migraine present for at least 12 months at the time of enrollment

• At least four "moderate to severe headache days" per month (by patient self-reportand then confirmed during four-week pre-randomization headache diary phase) A "moderate to severe headache day" is defined as a day during which there is aheadache of moderate to severe intensity that lasts for at least four hours, or aday on which a migraine-specific acute medication is taken to treat headache.

• If already taking a migraine preventive treatment, willing to continue with thattreatment without dose change during the first 16 weeks of the study, including the 4-week run-in phase and 12-week randomized phase.

• Not pregnant or breastfeeding

• Women of childbearing potential must agree to use effective methods of contraceptionto reduce the risk of pregnancy.

• Willingness and ability to provide informed consent.

• Willingness and ability to complete all research visits.

Exclusion Criteria:

• Contraindications to taking atogepant, propranolol, or topiramate.

• Currently taking atogepant, propranolol, or topiramate*

• Previously took atogepant, propranolol, or topiramate*

• Unwillingness to take atogepant, topiramate, or propranolol.

• Current use of a CGRP-targeting preventive medication or beta-blocker

• Migraine with brainstem aura

• Hemiplegic migraine

• Retinal migraine

• Migraine aura without headache (exclusively)

• Pure menstrual migraine

• Trigeminal autonomic cephalalgias

• Facial neuralgias

• Secondary headache disorders (medication overuse headache is not an exclusion)

• Migraine preventive treatment has been started or dose has been changed within 12weeks prior to potential enrollment.

• Used opioids or butalbital on five or more days per month on average for at least 3months prior to enrollment.

• Current or past epilepsy

• Severe hepatic impairment

• Moderate or more severe renal impairment * Occasional as needed use of propranolol,currently or in the past, is not an exclusion, such as taking as needed propranololfor treatment of anxiety.