PO-88 | Can tamoxifen and metformin nullify efficacy of CGRP-mAbs migraine prophylaxis?

Patrizia Rossi,^1,2 Valentina Cima,² Alessandro Burlina² | ¹Headache Center, ²Neurology Department, San Bassiano Hospital, Bassano del Grappa (VI), Italy

Background: Preventive treatment of migraine with CGRP-mAbs is a valid option in polypharmacy; there are no studies on the persistence of its efficacy with headache-inducing drugs. With Tamoxifen used for breast cancer, headache is a common side effect. With Metformin, a first-line treatment of type 2 diabetes, headache is not reported. According to the database drugs.com, less than 5% of users reported headache. We analyze the impact of tamoxifen and metformin in a patient treated with CGRP-mABs.

Methods: We collected 7 years headache diary of a 58-year-old woman with chronic migraine. Frequency, intensity, duration were summarized in a Total Pain Burden score (TPB), disability in MIDAS. Prophylaxes were propranolol, amitriptyline, botulinum toxin, topiramate and CGRP-mAbs. Furthermore: ramipril, tamoxifen, benzodiazepines, SRI, ASA, metformin.

Results: In 2018 during botulinum toxin, she started tamoxifen: TPB increased from 23 to 120 (+420%). During a 4-month tamoxifen withdrawal TPB decreased progressively (-85%) but worsened to 180 (+900%) after resumption, despite prophylaxes with topiramate, amitriptyline, propranolol. Subsequently she started CGRP-mAbs fremanezumab. In a quarter MIDAS decreased from 105 to 48 (-54%) and when tamoxifen was stopped, dropped to 6 and then 0. In May 2024 at the routine check-up she presented an unexpected daily high-intensity migraine, for the past 5 months: MIDAS 120, TPB 103. Her therapy was unchanged, except for the addition of metformin 1000 mg day. Neurological and general examination, brain CT, blood chemistry including fasting blood glucose were normal. We thought fremanezumab was no longer effective and discontinued it. Then measuring nocturnal glycemia we detected hypoglycemia. Metformin was discontinued and migraine disappeared at 3-month follow-up. After resumption (500 mg day), migraine started again without hypoglycemic episodes. Fremanezumab has been resumed with efficacy (-60%). The Naranjo algorithm evaluate correlation between metformin 1000 mg and migraine with level 9 (certain).

Conclusion: Tamoxifen worsens migraine both during conventional prophylaxis and during CGRP-mAbs. Metformin 1000 mg shows an unexpected significant worsening of migraine despite CGRP-mAbs, possibly side effect due to nocturnal hypoglycemia. The headache diary is a valid tool for the collection of information about prophylaxis-effectiveness, drugs consumption and interferences.