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Am J Psychiatry. 2000 Sep;157(9):1506-8.

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

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  • 1McLean Hospital, Belmont, MA 02478, USA.



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


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.


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.


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.

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