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Case Report Demonstrates Potential of CGRP-Targeting Medication to Treat Post-Subarachnoid Hemorrhage Headaches
Author(s):
Pankaj K. Agarwalla, MD
A case report recently published in Headache showed that use of erenumab (Aimovig; Amgen), an FDA-approved calcitonin gene-related peptide (CGRP) treatment, was successful in improving persistent refractory headaches in a patient with aneurysmal subarachnoid hemorrhage (aSAH). Overall, these findings point to the therapeutic potential of CGRP pathway-based therapies as an effective treatment for post-aSAH-headaches.1
In this unique case report, a 55-year-old man with past medical history of renal artery aneurysm, hypertension, and no prior history of headache presented to a clinical practice with persistent headaches which began after sustaining a Hunt Hess 3, modified Fischer 4 aneurysmal SAH at the age of 47, secondary to a ruptured anterior communicating artery aneurysm. The patient’s aneurysm was successfully treated with endovascular coil embolization followed by open craniotomy; however, following the procedure, he was left with severe, persistent, and daily throbbing headaches lasting several hours.
Led by Pankaj K. Agarwalla, MD, an assistant professor of neurosurgery at Rutgers Medical School in New Jersey, the patient tried several different medications before agreeing to try erenumab, a therapy that’s been on market since 2018. After receiving monthly injections of the therapy at 70 mg doses, he began to see gradual improvement in headaches. Over 18 months of therapy, headaches gradually decreased from daily occurrences to just 1 to 2 brief episodes per month, enabling the patient to taper off nortriptyline entirely.
The patient, who provided written informed consent to have his case published, saw sound sensitivity improved through erenumab treatment. More notably, he was able to leave his home, tolerate noisier environments, and return to work, further demonstrating the significant impact CGRP treatment had on him.
"In SAH, CGRP is released in a large bolus immediately after the hemorrhage," Agarwalla et al wrote. "With serum concentrations sharply rising and then dissipating by a month after the ictus, it is hypothesized to be released as a neuroprotective mediator in combating cerebral vasoconstriction. Regarding headaches, the large efflux of CGRP may lead to increased trigeminal hypersensitization and thus the development of chronic cephalgia."
Prior to erenumab, the patient’s neurological exam was unremarkable, aside from a mild postural tremor attributed to valproic acid, which was tapered successfully in favor of lamotrigine monotherapy. Over the following year, multiple treatment attempts, including acetaminophen tapering, supplements, acupuncture, and pharmacologic options like amitriptyline and nortriptyline, yielded limited success. Amitriptyline briefly reduced headache frequency but was discontinued due to side effects, and subsequent use of nortriptyline showed minimal benefit with continued adverse effects.
"The question of when to initiate anti-CGRP pathway therapy in the post-SAH period has not yet been explored and requires further clinical investigation,” the study authors wrote. “We recommend against initiation of therapy until the risk of delayed cerebral ischemia (DCI) is minimal—at least 3 to 6 weeks after ictus in our experience. The use of erenumab in our case was years after the window for cerebral ischemia attributable to DCI. Regarding the duration of therapy, the natural history of post-aSAH headache has been described in the literature to last from many months to even years after rupture. Therefore, the total duration of therapy may vary among patients. Importantly, erenumab is not metabolized by cytochrome P-450 enzymes and is therefore unlikely to interact with other drugs, such as anti-seizure medications, which induce or inhibit cytochrome P-450."
REFERENCE
1. Gandhi A, Quinoa TR, Geller E, Khandelwal P, Agarwalla PK. Erenumab in a patient with persistent headaches after subarachnoid hemorrhage: A case report of an effective treatment. Headache. 2025;65(2):373-376. doi:10.1111/head.14884
