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Brain kinetics of paroxetine and fluoxetine on the third day of placebo substitution: a fluorine MRS study.

OBJECTIVE
This study tested whether a relationship exists between concentration and response following discontinuation of selective serotonin reuptake inhibitors.


METHOD
Eight patients with remitted major depression who were taking 20 mg/day of either fluoxetine or paroxetine underwent placebo substitution for 3 days. Serum drug and brain fluorine levels were obtained before and after placebo substitution.


RESULTS
With placebo substitution, a mean of 88% (SD=13%) of brain fluorine signal from fluoxetine (plus fluorinated metabolites) remained, compared with a mean of 38% (SD=17%) of the brain fluorine signal from paroxetine (plus fluorinated metabolites). Among patients taking paroxetine, adverse events during placebo substitution correlated highly with steady-state brain drug levels.


CONCLUSIONS
The correlation of clinical effects with brain drug levels in the paroxetine group suggests that relationships between drug response and brain drug concentrations merit further investigation.