By Marcello Cherchi, MD PhD
For patients
Topiramate is sometimes used for the prevention of migraines, including migraines that cause disequilibrium.
For clinicians
Practical summary
Topiramate, originally developed as an anti-epileptic, is sometimes used in otoneurology for migraine prophylaxis, including for migraine associated vertigo. The main adverse effects at the doses used in otoneurology include word finding difficulties and nephrolithiasis.
Introduction
Topiramate was originally developed as an anti-epileptic medication, but over time has found other applications, including for migraine prophylaxis.
Pharmacology
Topiramate is a sulfamate-substituted monosaccharide with a broad spectrum of activity. Postulated mechanisms of action include modulation of voltage-dependent sodium channels, potentiation of gamma-aminobutyric acid inhibition, block of excitatory neurotransmission, modulation of voltage- and receptor-gated calcium ion channels, and carbonic anhydrase inhibition (Khalil et al. 2019). Topiramate is not extensively metabolized (though some proportion undergoes oxidation and hydrolysis), and it is primarily renally excreted (Khalil et al. 2019).
Adverse effects
At the doses prescribed in otoneurology and neurotology, the main adverse effects of which the clinician should be aware include word-finding difficulties and nephrolithiasis.
Cautions and contraindications
Given the potential for the adverse effect of word-finding difficulties, topiramate is probably not a good first choice medication for cognitive workers who rely heavily on language, such as attorneys or journalists. Since topiramate can also elevate the risk of developing nephrolithiasis, it is probably not a good first choice medication for patients with a prior history of kidney stones. Topiramate is relatively contraindicated in pregnancy and nursing.
Relevance in otoneurology
The main application of topiramate in otoneurology is in the prophylaxis of migraine and migraine associated vertigo. Several prospective randomized placebo-controlled trials have shown topiramate to be superior to placebo for migraine prophylaxis (Brandes et al. 2004; Silberstein et al. 2004), and the results of other types of studies concur with this conclusion (Silberstein 2017).
References
Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, Neto W, Schwabe S, Jacobs D (2004) Topiramate for migraine prevention: a randomized controlled trial. Jama 291: 965-73.
Khalil NY, AlRabiah HK, Al Rashoud SS, Bari A, Wani TA (2019) Topiramate: Comprehensive profile. Profiles Drug Subst Excip Relat Methodol 44: 333-378. doi: 10.1016/bs.podrm.2018.11.005
Silberstein SD (2017) Topiramate in Migraine Prevention: A 2016 Perspective. Headache 57: 165-178. doi: 10.1111/head.12997
Silberstein SD, Neto W, Schmitt J, Jacobs D (2004) Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol 61: 490-5.
