LOW SERUM LEVELS OF TRICYCLIC ANTIDEPRESSANTS IN AMITRIPTYLINE-TREATED AND DOXEPIN-TREATED INPATIENTS WITH DEPRESSIVE SYNDROMES ARE ASSOCIATED WITH NONRESPONSE

Nonresponse to tricyclic antidepressant (TCA) treatment is observed in about one-third of depressed patients. The cause(s) for nonresponse - apart from disease-specific effects - might be the failure to build u p sufficiently high serum TCA levels due to noncompliance, substance a buse, rapid metabolism, or low dose. We carried out a retrospective an alysis relating antidepressant serum levels to patient data obtained i n the naturalistic setting of the Psychiatric Hospital of the Bonn Uni versity during the introductory phase of drug-monitoring. Case reports of 110 depressed inpatients who were treated with amitriptyline or do xepin were analyzed with respect to the following: medication and come dication, daily dose, type and duration of treatment, serum TCA concen trations (analyzed by the fluorescence polarization immunoassay), age, sex, body weight, abuse of nicotine or alcohol intake, serum transami nases (ALT, alanine aminotransferase, and AST, aspartate amino transfe rase), gamma-glutamyltranspeptidase (gamma-CT) and creatinine, complia nce, and response. The salient findings were: 1. Serum TCA concentrati ons increased linearly with the daily amitriptyline dose but not with that of doxepin. 2. Interindividually, there was an eight to ten-fold difference in serum TCA concentrations at steady-state with 150 mg/day of either drug; longitudinally, we observed intraindividually a coeff icient of variation of 8% and 12% for amitriptyline and doxepin respec tively. 3. With amitriptyline (150 mg/day), the correlation between ag e and serum TCA concentrations was low (r = 0.33, p < 0.055) and no co rrelation was found after the administration of doxepin (150 mg/day), nor was there any correlation between age and dose-adjusted serum TCA concentrations after the administration of either drug. 4. Nonresponde rs had significantly lower serum levels than responders. These results suggest that patients should not qualify as nonresponders unless it c an be demonstrated (and it is clinically applicable) that the steady-s tate serum TCA levels are stable within the upper limit of the recomme nded therapeutic range and serum level.