The hypothesis of a relationship between drug concentrations in blood and in brain represents the basis for therapeutic drug monitoring of psychotropic drugs (TDM). However, available techniques do not allow to analyse separately the parent compound and its active metabolites in tissues of the central nervous (CNS) system, but cerebrospinal fluid (CSF) represents an accessible fluid, In order to evaluate the relationship between blood and CSF drug concentrations and its biological and clinical effect, plasma and CSF concentrations of the enantiomers of citalopram, its N-de-methylated (DCIT) and deaminated (CIT-PROP) metabolites were measured in plasma and CSF in 22 depressed patients after a 4-week treatment with 40 mg/day citalopram. CSF 5-HIAA and HVA were measured at baseline and after the 4-week citalopram medication period. Patients were assessed clinically, using the Hamilton depression rating scale (21-item HAM-D). Responders were defined by a >= 50% decrease of the HANI-D score (Delta HANI-D) after the 4-week treatment. CSF concentrations of S- and R-Citalopram were 10.6 +/- 4.3 ng/ml and 20.9 +/- 6 ng/ml, respectively and their CSF/plasma ratios were 52% 9% und 48% 6%, respectively. The Citalopram treatment resulted in a significant decrease (28%) of 5-HIAA and a significant increase (41%) of HVA in CSF. A HAM-D correlated significantly with CSF S-Citalopram (p < 0.05), CSF S-CIT-PROP (p=0.01) and 5-HIAA decrease (p=0.01). The demonstrated correlations between pharmacokinetic parameters and the clinical outcome as well as 5-HIAA changes indicate that monitoring of plasma S-Citalopram, CSF S-Citalopram- and CSF S-CIT-PROP may be of clinical relevance