OPEN-LABEL DOSAGE AND TOLERABILITY STUDY OF TIAGABINE MONOTHERAPY IN PATIENTS WITH REFRACTORY COMPLEX PARTIAL SEIZURES

This study was designed to determine the highest tiagabine dosage that could be administered as monotherapy to patients with complex partial seizures refractory to treatment with other antiepileptic drugs (AEDs ) without unacceptable adverse events. Thirty-one patients, 18-47 year s of age, participated at three sites. During a 3-week initiation phas e, tiagabine was started and the dosage increased while concomitant AE D dosage was reduced. During a 7-week dose-evaluation phase, dosage wa s adjusted until the maximum tolerated dosage was reached. During the dose termination phase, patients tolerating the drug entered a long-te rm open-label study of tiagabine monotherapy. Of 31 patients, 19 conve rted to monotherapy; in 12 cases, monotherapy was tolerated well enoug h to be continued for 7 weeks. Of the 12 nonconverters, seven left dur ing the initiation phase due to adverse events and five due to inadequ ate seizure control. Most events were mildly or moderately severe and were associated with the central nervous system. Plasma tiagabine conc entrations were similar in both converters and nonconverters. Conversi on to tiagabine monotherapy was accomplished in most patients with dif ficult-to-control seizures when previous AED monotherapy was replaced in under 4 weeks. The ideal dosage appeared to be approximately 38 mg/ day given in three divided doses. (C) 1998 by Elsevier Science Inc. Al l rights reserved.