Various aspects of Pregabalin effectiveness as add-on therapy in patients with refractory epilepsy

The purpose of the study was to perform an open, prospective study on various aspects of PGB effectiveness in Bulgarian patients with drug-resistant epilepsy. It was open, prospective and was performed with the participation of patients with epilepsy who attended the Clinic of Neurology at the University Hospital in Plovdiv, Bulgaria for a regular examination in cases of unsatisfactory seizure control or for adverse events from treatment. Patients completed diaries about seizure frequency, severity, and adverse events. There were regular documented visits at 3 or 6 months during the first year of treatment with pregabalin (PGB) and at 6 months or 1 year afterwards, with dynamic assessment of seizure frequency, severity, adverse events, and EEG recordings. PGB was applied as add-on treatment in 47 patients (24 males, mean age 34 years) with long duration of epilepsy, manifested with predominantly severe and very frequent partial, a combination of partial and generalized or generalized tonic-clonic seizures, refractory to the prescribed, usually combined treatment with a variety of AEDs. There was relatively mild, stable though, dynamic improvement of seizure severity,  satisfactory seizure frequency reduction in 43.5% of participants, stable mean seizure frequency reduction (48-51%) from the 6-th to the 24-th month of the study, as well as a high and stable responder rate (58.7-62.5%) during the same period. New seizure types (generalized tonic-clonic, generalized atonic) appeared in 2 patients. The final clinical efficacy was higher in patients without seizure clusters or status epilepticus in the disease course. EEG improvement was found in a small percentage of patients (less than a third) and it did not correlate with clinical findings and their dynamics. Adverse events (dizziness/vertigo, sleepiness, memory impairment, increased weight, diplopia, lymphadenomegaly, impaired concentration, gastro-intestinal discomfort, transient leucopenia, rash, nausea, anxiety) were reported in 25.53% of patients. They were usually severe and became a cause of treatment termination in 12.8% of patients. In conclusion, PGB treatment is associated with: low and stable improvement of seizure severity, good and stable reduction of seizure frequency, a possibility of seizure control worsening, possible appearance of new seizure types, rare EEG dynamics, acceptable safety and tolerability.