Pharmacopsychiatry 2005; 38 - 64
DOI: 10.1055/s-2005-862677

Clinical Relevance of Citalopram (CIT) Plasma and Cerebrospinal Fluid (CSF) Concentrations: Impact with CSF Monoamine Metabolites

G Nikisch 1, AA Mathé 2, P Baumann 3
  • 1Klinikum Fulda, Department of Psychiatry and Psychotherapy, Fulda, Germany
  • 2Department of Physiology and Pharmacology, Division of Pharmacology, Karolinska Institute, Stockholm, Sweden
  • 3Unité de Biochimie et Psychopharmacologie Clinique, University Department of Adult Psychiatry, Centre of Psychiatric Neurosciences, Prilly-Lausanne, Switzerland

Therapeutic drug monitoring (TDM) of new generation antidepressants is part of a controversial discussion, since most of the cited studies found no proof for the existence of a therapeutic window for these drugs. Plasma and CSF concentrations of the enantiomers of CIT, its N-demethylated metabolite demethylcitalopram (DCIT) and its deaminated metabolite citalopram propionic acid derivative (CIT-PROP) were measured in plasma and CSF in twenty-two depressed patients after a 4-week treatment with 40mg/day citalopram. CSF 5-HIAA and HVA were measured at baseline and after the 4-week CIT medication period. Patients were assessed clinically, using the 21-item HAM-D scale: at baseline and then at weekly intervals. CSF concentrations of S-CIT and R-CIT were 10.6±4.3 ng/ml and 20.9±6 ng/ml, respectively and their CSF/plasma ratios were 52%±9% and 48%±6%, respectively. The CIT treatment resulted in a significant decrease of 5-HIAA and a increase of HVA in CSF. A frequently reported correlation between 5-HIAA and HVA was also found. ΔHAM-D correlated significantly with CSF S-CIT, CSF S-CIT-PROP and Δ5-HIAA. The demonstrated correlations between pharmacokinetic parameters and the clinical outcome as well as 5-HIAA changes indicate that monitoring of plasma S-CIT, CSF S-CIT- and CSF S-CIT-PROP may be of clinical relevance.

References: G. Nikisch, A.A. Mathé, A. Czernik, C.B. Earp, P. Jiménez-Vasquez, M. Brawand-Amey, P. Baumann. Stereoselective Metabolism of Citalopram in Plasma and Cerebrospinal Fluid (CSF) of Depressive Patients: Relationship with 5-HIAA in CSF and Clinical Response. J Clin Psychopharmacol. 2004; 24:1–8.