“We think that, by modulating cerebrospinal fluid pressure and reducing intracranial venous sinuses compression, these drugs produce a decrease in the release of calcitonin gene-related peptide (CGRP), a key migraine-promoting peptide”, Dr Braca explained. “That would pose intracranial pressure control as a brand-new, pharmacologically targetable pathway.”
I'm not sure I understand what that means, but I wonder if this would work for people who are not obese?
Anecdotes are not data, however I used to have one or more severe migraine headaches weekly. Debilitating migraines. I suffered pretty high blood pressure (which has a very direct relationship with cerebrospinal fluid pressure, which is why I mention this), but aside from that am very healthy and physically fit, exercise regularly, and so on.
I started medication to treat the BP -- telmisartan and amlodipine -- and my BP dropped from 150+/120+ to 115/80. The migraines completely disappeared. I still infrequently get the visual aura that would traditionally precede a migraine, but nothing follows. I haven't had a migraine in the years I've had my BP under control.
Candesartan is actually one of the most used medications for migraine prophylaxis, also for people with normal BP. Your doc might have chosen the med for that reason. Though it's widely used for BP even in people without migraines.
I've had the auras at least since a teenager, but not headaches. Thought is was completely normal, 'til a neurologist said No and that I has having vestibular migraines. Blood pressure was always on the low side of normal.
Family history of migraines and seizures, which some hypothesize have the same root causes. Would be interesting to see GLP-1 tests on epilepsy.
They are positing that the GLP-1 agonist acts mechanistically to modulate CGRP release. But CGRP involvement in migraine is itself only one potential mechanism that causes migraine. I would like to know whether the subjects who responded to the GLP-1 therapy were also responsive to CGRP monoclonal antibody therapy.
My wife has chronic migraines which are successfully mitigated by rimegepant (gepants are CGRP antagonists), and didn't have any particular change in headaches from GLP-1.
What has helped, interestingly, is supplemented creatine HCl (she went with hcl because it's absorbed substantially faster than monohydrate). We've learned that depletion of neural ATP levels can result in an energy crisis which results in cortical spreading depression, which stimulates the release of CGRP. (https://www.sciencedirect.com/topics/neuroscience/spreading-...)
She's found that a) daily supplementation of creatine has reduced her headache days, and b) an immediate dose of creatine upon onset of a headache frequently aborts or mitigates it. Her need for the gepants has dropped to a tiny fraction of what it was prior to starting creatine.
She's tried everything under the sun, had all the scans, tried all the meds and procedures, and creatine and gepants are the only things she's found that have worked. She's not a placebo responder, and hasn't responded to about a zillion other therapies, so we're pretty sure it's not just placebo effect.
