Pregabalin is an effective add-on treatment for focal seizures. The guideline sum­mary recommends that pregabalin can effectively reduce the frequency of seizures in adults with refractory focal epilepsy (Grade A) [488]. To evaluate the efcacy and tolerability of pregabalin as an add-on treatment for drug-resistant focal epilepsy, two groups [489, 490] conducted a systematic review of nine randomized controlled trials. The results showed that pregabalin, as an add-on treatment for refractory focal epilepsy, was signicantly more effective than placebo in reducing seizures by 50% or more and attaining seizure freedom. Furthermore, there was a certain dose– response relationship. Doses ranging from 150 to 600mg/day were effective. As the dose increased from 300 to 600mg/day, the chance of a response doubled, but toler­ability issues occurred at higher doses. Compared with patients taking lamotrigine, patients taking pregabalin were more likely to have a 50% or greater reduction in seizure rates, but there was no signicant difference in seizure-free status between patients taking each of the two drugs. Compared with those taking levetiracetam, there was no signicant difference in the 50% or greater reduction in seizure rates among patients taking pregabalin, but there was a relatively lower seizure-free rate in patients who received an addition of pregabalin. However, the trials included in this review were short in duration. Longer-term trials are needed to inform clinical decisions.

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is usu­ally poorly controlled with antiseizure drugs. Androsova etal. [492] conducted a study on the efcacy, tolerability and retention rate of different ASMs in the treat­ment of MTLE-HS.For comparison, a total of 3249 trials were included, with a total of 767 patients. There were 73 patients who received PGB.The results showed that most (92.1%) of the PGB was added as a third drug, with an average maximum dose of 300mg/day and an average treatment time of 10±9.8months. Compared with CBZ and levetiracetam, only 4.7% of patients were seizure free after 12months of PGB treatment. The therapy failure rate was 41.9%. The incidence of adverse reactions was high (27.4%), and the most common adverse reactions were drowsi­ness and weight gain. In addition, the retention rate of PGB was the lowest (40%). The authors held that PGB had no obvious advantage in treating seizures in patients with MTLE-HS.

Mann etal. [498] used video electroencephalography (VEEG) monitoring to evalu­ate the efcacy and safety of pregabalin as an add-on treatment for focal epilepsy in children (1month to 4years old). They randomized 175 pediatric patients (mean age 28.2months, 59% male) at a 2:1:2 ratio to receive 7mg/kg/day pregabalin, 14mg/kg/day pregabalin or placebo. The results showed that compared with that in the placebo group (n=53, P=0.022), the 24-h seizure rate was 35% lower in the PGB 14mg/kg/day (n=28) group. However, the seizure rate in the PGB 7mg/kg/ day (n=59) group did not signicantly improve. In addition, the most common AEs in the PGB 7mg/kg/day, 14mg/kg/day, and placebo treatment groups were somno­lence (11.3%, 17.6%, and 5.7%, respectively) and upper respiratory tract infection (7.0%, 11.8%, and 11.4%, respectively). The severity of all AEs was mild to moder­ate. The authors considered that 14mg/kg/day pregabalin could signicantly reduce the rate of focal seizures in children. Pregabalin at 7mg/kg/day and 14mg/kg/day was generally safe and well tolerated in children aged 1month to 4years.

Serotonin syndrome (SS) is a potentially fatal clinical syndrome caused by drugs with serotonergic properties. Prakash etal. [506] conducted a systematic review of case reports of SS associated with antiseizure drugs. Of the 76 patients enrolled, seven patients with SS were exposed to pregabalin at a median dosage of 150mg/ day. In four of these studies, there was a temporal association between PGB intake and the occurrence of SS.All patients with pregabalin-induced SS were also treated with another serotonergic agent. The main manifestations of SS induced by PGB include confusion, agitation, hallucinations, tremors, myoclonus, sweating, nausea, diarrhea, fever, hypertension, etc. The authors noted a need to be alert to the possi­ble incidence of SS induced by PGB, especially in patients taking another seroto­nergic drug at the same time.