Concentrations of Venlafaxine, Mirtazapine and Citalopram in serum and cerebrospinal fluid – a naturalistic approach

Objectives: The ability of psychotropic drugs to pass the blood brain- and blood CSF-barrier depends on several properties of the drugs (e. g. lipophilicity, molecular size). Aim of this study was to investigate the relation of drug concentrations of different antidepressants in plasma and cerebrospinal fluid (CSF) as well as its relation to the administered daily dose of the drugs. Methods: Three groups (venlafaxine [VEN], n = 16, mirtazapine [MIR], n = 16 and citalopram [CIT], n = 20, of both sexes) were analyzed. All patients were on a stable therapy with fixed daily doses for at least seven days in a naturalistic clinical setting and underwent lumbar puncture for medical reasons. The correlation of drug levels in the blood, drug levels in the CSF and the daily dose of the drugs were calculated. Results: A strong correlation could be observed for VEN in plasma and CSF (p < 0.001). MIR in plasma and CSF were just trend-wise correlated (r = 0.441, p = 0.088) and no relation of daily dose and CSF levels of MIR could be observed (r = 0.313, p = 0.238). CIT levels showed a strong correlation between plasma and CSF (r = 0.890, p < 0.001). Conclusion: For the investigated antidepressants a (strong) relation of drug levels in serum and CSF could be observed, but the plasma and CSF concentrations do not reflect the administered daily dose of the drugs proper. These finding indicate that that therapeutic efforts should be driven by serum concentration rather than by dose optimization.