Duloxetine enters the brain - But why is it not found in the cerebrospinal fluid

- Unlike other antidepressant drugs, duloxetine is hardly found in CSF.
- Low concentrations are indicative for a low penetration into or an active transport out of the CSF.
- Sufficiently high drug levels at the target sites are not reflected in CSF concentrations.

BackgroundAntidepressants enter the brain to reach their site of action in a different extent. However, there has been no study to date about duloxetine's ability to enter the brain and cerebrospinal fluid. Aim of this study was to measure blood and cerebrospinal fluid concentrations of duloxetine and to account for the distribution between the two compartments.MethodsConcentrations of duloxetine were measured in blood serum and cerebrospinal fluid 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.ResultsSerum 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 and limitationsContrasting to own preceding studies on venlafaxine, mirtazapine and citalopram with comparably high concentrations in cerebrospinal fluid, the here presented findings indicate that duloxetine shows a very different distribution pattern. Very low concentrations in the cerebrospinal fluid 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 concentrations 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.