If you’ve ever experienced a migraine you know how debilitating they can be. Now imagine suffering from episodic migraines and having up to 14 migraine days a month or having chronic migraines and having at least 15 migraine days a month. That’s what I was going through during my junior year of undergrad. I was having up to 13 migraine days a month and my quality of life took a large hit. I started missing class on a semi-regular basis since my migraines were both light and sound sensitive. Most days I could hardly leave my room because my migraines were so debilitating. I’m sure many of you have seen the TV commercials for medications such as Emgality or Aimovig, and if you have seen these commercials you know that they do not provide information as to how these medications work.
I have been using the migraine medication Ajovy for 15 months now and I can tell you that this medication has significantly improved my quality of life. The medications Emgality, Aimovig, and Ajovy all work in similar ways. The patient gives themself a subcutaneous injection monthly or quarterly depending on the specific medication and severity of their migraines. All of these medications are monoclonal antibodies against the calcitonin gene-related peptide (CGRP) itself or its receptor (González-Hernández et. al., 2020). Monoclonal antibodies are broken down by renal proteolysis into short peptides and amino acids (González-Hernández et. al., 2020). This breakdown does not result in any toxic intermediates meaning that the liver will not be damaged in any way (González-Hernández et. al., 2020). It has been found that the pathophysiology of a migraine consists of a critical neurophysiology state that results in a low plasma concentration of serotonin, and a high plasma concentration of CGRP (González-Hernández et. al., 2020). The release of CGRP results in vasodilation and sensitization of nociceptive pathways (González-Hernández et. al., 2020). Being able to prevent this release is the goal of antimigraine medications. Ajovy and Emgality work by scavenging the circulating CGRP molecules whereas Aimovig works against the receptor itself (González-Hernández et. al., 2020). The most common adverse reaction is an injection site rash (Ajovy-pi.pdf. n.d.). Both monthly and quarterly injections of Ajovy have shown statistically significant improvement when compared to a placebo (Ajovy-pi.pdf, n.d.). Overall, these medications have been shown to be very effective and have very minimal side effects.
References:
Ajovy-pi.pdf. (n.d.). Retrieved September 18, 2020, from https://www.ajovy.com/globalassets/ajovy/ajovy-pi.pdf
González-Hernández, A., Marichal-Cancino, B. A., Gracía-Boll, E., & Villalón, C. M. (2020). The locus of Action of CGRPergic Monoclonal Antibodies Against Migraine: Peripheral Over Central Mechanisms. CNS & Neurological Disorders – Drug Targets, 19. http://doi.org/10.2174/1871527319666200618144637
Thanks for sharing Madison! I'm so sorry to hear that you were experiencing so many migraine days a month. That sounds miserable. I'm glad to hear that your symptoms have much improved with Ajovy!
ReplyDeleteFrom what I've read on my own about migraines is that they are complicated to treat, and there does not seem to be a "one-size fits all" approach for them. From your post, I thought it was interesting that low plasma serotonin levels are part of the cause of migraines. I guess this makes sense with why some people's migraines are successfully treated with tricyclic antidepressants. I went down a bit of a rabbit hole, reading about the use of antidepressants to treat migraines. I thought it was interesting that SSRIs and SNRIs, which both are involved in serotonin reuptake, are not demonstrated to help treat migraines though. I wonder why this is? Do they think that the low serotonin levels cause elevated CGRP or vice-versa?
Anyways, thanks for sharing!
Swanson, J. W., MD. (2019, May 10). Can antidepressants help with migraines? Retrieved September 21, 2020, from https://www.mayoclinic.org/diseases-conditions/migraine-headache/expert-answers/migraine-treatment/faq-20058410
I found the pathophysiologic explanation of migraines fascinating and I am curious as to how this can tie into menstrual migraines. Menstrual migraines are believed to occur due to the decrease of estrogen during the menstrual cycle (Allais et al., 2018) and are commonly treated with an estrogen supplement (MacGrefor EA., 2009). Estrogen can modulate neuronal excitability, through serotonin (Allais et al., 2018). This shows a relationship between the pathophysiology of menstrual migraines and the two common factors that play a role in the overall pathophysiologic explanation of migraines. Research shows that estrogen leads to an overall increase in serotonin synthesis and availability (Hall E. and Steiner M., 2013). Consequently, this may allow us to say that estrogen supplements are an effective menstrual migraine treatment purely through increasing serotonin levels and do not directly act on the CGRP. This leads me to believe there is a negative feedback loop between estrogen and CGRP. In fact, I was able to find a study that proved serotonin receptor agonists to be effective in bringing CGRP back down to normal levels (Aggarwal et al., 2012). In conclusion, estrogen increases serotonin levels, that can then decrease elevated CGRP levels. With this knowledge can we propose that abnormal estrogen levels are the root cause of migraines in general? If so, this may account for why women are more predisposed to migraine attacks (Aggarwal et al., 2012).
ReplyDeleteAllais G, Chiarle G, Sinigaglia S, Airola G, Schiapparelli P, Benedetto C. Estrogen, migraine, and vascular risk. Neurol Sci. 2018 Jun;39(Suppl 1):11-20. doi: 10.1007/s10072-018-3333-2. PMID: 29904828.
MacGregor EA. Estrogen replacement and migraine. Maturitas. 2009 May 20;63(1):51-5. doi: 10.1016/j.maturitas.2009.03.016. Epub 2009 Apr 16. PMID: 19375252
Hall E, Steiner M. Serotonin and female psychopathology. Womens Health (Lond). 2013 Jan;9(1):85-97. doi: 10.2217/whe.12.64. PMID: 23241157
Aggarwal M, Puri V, Puri S. Serotonin and CGRP in migraine. Ann Neurosci. 2012 Apr;19(2):88-94. doi: 10.5214/ans.0972.7531.12190210. PMID: 25205974; PMCID: PMC4117050.