Duloxetine enters the brain – but why is it not found in the cerebrospinal fluid

Objective: Antidepressants enter the brain to reach their site of action. However, little is known about duloxetineʼs ability to enter the brain and cerebrospinal fluid (CSF). Aim of the study was to measure blood and CSF concentrations of duloxetine and to account for the distribution between the two compartments. Method: Concentrations of duloxetine were measured in blood serum and CSF of 19 patients treated with daily doses of 30–120 mg. Daily doses were correlated with serum and cerebrospinal fluid concentrations and serum concentrations were correlated with concentrations in cerebrospinal fluid. Results: Serum concentrations of duloxetine showed a moderate but significant correlation with the applied daily dose, r = +0.473, p = 0.04. Duloxetine concentrations in the cerebrospinal fluid above the designated limit of quantification of 2.0 ng/mL were only found in three of the 19 patients. Conclusions: Contrasting to own preceding studies on different antidepressants, the findings indicate a very different distribution pattern. Very low concentrations in the CSF may be due to the fact that the drug crosses the blood-cerebrospinal fluid barrier much worse than other antidepressants do, suggesting a low ability of duloxetine to enter the brain. Alternatively, low drug levels may be interpreted in a sense of a missing residence time in cerebrospinal fluid due to active transport mechanisms out of this environment either back into the bloodstream or into the brain.