Presurgical trials with video-electroencephalogram (EEG) monitoring for a couple of days provide the possibility to objectively and quantitatively analyze seizure activity during different drug treatments. Patients are provided with the optimal medical care and safety precautions when hospitalized. Hereby a method used in the antiepileptic drug (AED) trials called therapeutic intensive seizure analysis (TISA) has been recently introduced, by which AED efficacy on seizure activity can be objectively quantified by using continuous video-EEG monitoring. This could be used not only as a supplement to the traditional evaluation of AEDs' efficacy by treatment failure designs in large groups, but also can provide early individual information on the changes of seizure activity of each patient during the therapy. Data from TISA studies suggest that secondarily generalized tonic-clonic seizures (SGTCs) mostly occur in patients with a SGTC history after withdrawal of AED. The first 3 days of titration of a newly introduced AED was important for efficacy assessment; with a low risk of SGTCs. By using the TISA method an early recognition of first effects of a new AED on seizure activity and neuropsychological changes is possible, which can be correlated to serum concentration levels in a small sample size. The essentials of the proposed modification to the conventional presurgical trial are: (1) a complete withdrawal of AEDs should be avoided, if possible and (2) a titration phase limited to 3 days is suggested, using a condensed evaluation setting including the TISA method, serum concentration and neuropsychological monitoring. In addition long-term effects can be evaluated by repeated video-EEG monitoring.