Molecular mechanisms of topiramate and its clinical value in epilepsy

Topiramate (TPM) is widely used as monotherapy or add-on therapy in adults and children (aged 2 to 16 years) with primary generalized tonic-clonic seizures or focal-onset seizures. TPM has also expanded its treatment spectrum to other seizure types and epileptic encephalopathies. Moreover, TPM has beneficial effects in some comorbidities of epilepsy such as migraine/headache and obesity. Interestingly, it also exhibited neuroprotective effects in several preclinical studies. The most common side effects of TPM are generally mild to moderate, including somnolence, dizziness, fatigue, insomnia and weight loss, which may be reduced through starting with a low dose and slowing titration to effective dosages. The mechanisms underlying the antiepileptic effect and adverse reactions of TPM have been extensively studied in the past 14 years since the last comprehensive review of TPM. Multiple mechanisms including but not limited to: (1) blockade of voltage-gated Na⁺ channels, (2) inhibition of voltage-gated Ca²⁺ channels, (3) inhibition of glutamate-mediated neurotransmission, (4) inhibition of carbonic anhydrase isoenzyme, as well as (5) enhancement of GABA-mediated neurotransmission are involved in its antiepileptic effect. In this review, we aim to summarize the mechanisms, clinical benefits and adverse reactions of TPM in epilepsy treatment, and to briefly discuss the prospects of TPM.