The difference between Therapeutic Drug Monitoring (TDM) and uncontrolled therapy consists in the fact that in TDM we can predict a certain scheme of treatment according to clinical and laboratory results. It is a method which serves to increase the efficacy and safety of pharmacotherapy in an individual patient. This paper presents the results of the treatment with tricyclic antidepressants based on the monitoring of serum drug level in 32 patients with indications for using pharmacogenetic as well as pharmacoelectroencephalographic tests. Clinical status of the patients was evaluated according to: Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Clinical Global Impression Scale (CGIS), and TCA concentration in serum was determined using Fluorescence Polarization Immunoassay (FPIA). Hydroxylation phenotype was determined using debrisoquine as a model drug. EEG was recorded in four leads: F3-C3, F4-C4, P3-O1, P4-O2. In the present study, we did not found any significant correlation between clinical status and serum TCAs concentrations measured by FPIA method. Efficacy of antidepressant treatment and stabilization of serum TCA concentrations depended largely upon the time course of the treatment. Debrisoquine phenotyping revealed the presence of one poor metabolizer (MR = 15) in the examined group of patients. A significant improvement in the clinical status of the patients, the stabilization of therapeutic drug concentrations, the appearance of antidepressive profiles in the pharmaco-EEG profile after 14 days of therapy, as well as the starting value determined by SERS were shown to be prognostic factors for the further antidepressant therapy.