Clinical pharmacology of topiramate in migraine prophylaxis: efficacy and safety

Topiramate is generally considered to be safe and well tolerated in migraine treatment. The most common AE, which appeared with a frequency at least of 5% in controlled clinical trials on topiramate in migraine prophylaxis, were paresthesia, fatigue, anorexia, nausea, upper respiratory tract infection, diarrhoea, dizziness, difficulty with memory, language problems, difficulty with concentration and attention. The majority of AE were mild to moderate in severity and were most common during titration period rather than maintenance phase of the treatment. The incidence of AE leading to suspension of topiramate or to a dose reduction appeared to be dose-dependent. The most common were paresthesia (7%), fatigue (4%), nausea (4%), difficulty with concentration/attention (3%), insomnia (3%), anorexia (2%) and dizziness (2%) [Adelman 2008]. Paresthesia, usually tingling of the extremities, occurred with a frequency of 50% in the migraine patients treated with topiramate 100 mg/day but led to treatment discontinuation only in 8% of patients. Peripheral carbonic anhydrase inhibition by topiramate is thought to underlie the occurrence of paresthesia. Migraine patients seem exceptionally susceptible to paresthesia compared with patients with other diseases [Luxic]. However, it has been suggested that the development of paresthesia could predict a favorable response to topiramate in migraine prophylaxis [Lee 2007].