Objective:To ensure more efficient and safe antidepressive treatment in elderly.
Design:Correlations between clinical state, serum level of drugs and pharmaco-EEG profile in young and elderly depressives.
Materials and Methods:Thirty three young (11 M, 22 F, mean age: 42.6, range: 24-58) and 14 (3 M, 11 F, mean age: 65.6, range: 60-74) elderly inpatients with DSM-IV major depressive disorder have completed the study. After at least one week washout, 41 and 6 patients were started openly either on tricyclic antidepressants or fluoxetine. Clinical state, drug serum level and EEG profile were evaluated before entering the study, after 3-6 and 24 hrs, and 2, 4, 6, 8 weeks of treatment. The Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS) and the Side Effects Rating Scale (SERS) were used to assess clinical state. Debrisoquine hydroxylation phenotype was determined. Serum drug concentrations were measured using Fluorescence Polarization Immunoassay and High Performance Liquid Chromatography. Change from baseline quantitative EEG was analyzed. The EEG was obtained from 4 bipolar derivations (F3-C3, P3-O1 and F4-C4, P4-O2) and subjected to spectral analysis.
Results:Two patients were poor hydroxylators and 1 patient was an ultrarapid metabolizer. Eventually, scores on the HDRS of 21 young and 6 elderly depressives showed at least 50% reduction at the sampling end point. Clinical improvement as measured by means of HARS was also found in 23 young and 7 elderly patients. The results did not differ significantly between the groups. Theta and alpha-2 relative power differentiated responders and nonresponders after 8 weeks of treatment. Responders showed significant decreases in theta power in P3-O1 (t=2.24, p=0.03) and P4-O2 (t=2.00, p=0.05). Increased alpha-2 power was found, in P3-O1 (t=2.48, p=0.02) and P4-O2 (t=2.89, p=0.006). Lower scoring on HDRS was associated with greater theta power decrease (P3-O1: rho=-0.458, p=0.003; P4-O2: rho=-0.419, p=0.008) and greater alpha-2 increase (P3-O1: rho=0.0429, p=0.006; P4-O2: rho=0.43, p=0.006). No pharmaco-EEG differences were found between the groups. There was also no significant difference between the side effects in both groups when comparing their scores on SERS. However, the scores on SERS were significantly higher in nonresponders than in responders on each of sampling days. A significant inverse correlation between lower scoring on HDRS after 8 weeks of treatment and increased side effects on each of sampling days (rho=-0.40, -0.40, -0.40, -0.42, -0.53, -0.56, -0.66) was found.
Conclusion:In this preliminary approach, efficacy and time course of antidepressive therapy were not related to age. Therapeutic drug monitoring and pharmaco-EEG contribute to rational treatment, however, monitoring of adverse effects occurred to be of the greatest predictive value.
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