Am J Psychiatry 1996; 153:1450-1454
Copyright © 1996 by American Psychiatric Association
Are fluoxetine plasma levels related to outcome in obsessive-compulsive disorder?
LM Koran, JW Cain, RA Dominguez, AJ Rush and S Thiemann
Department of Psychiatry, Stanford University School of Medicine, CA, USA.
OBJECTIVE: In obsessive-compulsive disorder, the relationship between blood
levels of serotonin reuptake inhibitors and clinical outcome is unclear. In
a multicenter trial, the authors examined the relationship between steady
state plasma levels of fluoxetine and norfluoxetine (determined after 7
weeks of treatment), and their sum, and clinical outcome. METHOD: Ratings
of symptom severity of obsessive-compulsive disorder (Yale-Brown Obsessive
Compulsive Scale scores) were obtained at baseline and after 13 weeks for
200 adult outpatients with moderately severe obsessive-compulsive disorder
treated with fluoxetine doses of 20 mg/day (N = 68), 40 mg/day (N = 64),
and 60 mg/day (N = 68). RESULTS: Mean plasma levels of fluoxetine and
norfluoxetine were statistically significantly higher with higher dose.
Statistical analyses revealed no significant relationship for plasma level
of either molecule or their sum in predicting endpoint percent change in
obsessive-compulsive scores. Plasma levels of patients with a marked
response (decrease of 50% or more in obsessive-compulsive score) did not
differ significantly from those of nonresponders (less than a 25% decrease
in obsessive-compulsive score). No hint was seen of a therapeutic window or
of a relationship limited to one gender or within the lowest dose group (20
mg/day). However, since S-norfluoxetine is a much more potent serotonin
reuptake inhibitor than R-norfluoxetine, the absence of chiral
(stereospecific) assays in this study limits the results. CONCLUSIONS:
Steady state plasma levels of fluoxetine and norfluoxetine are not related
to clinical outcome in patients with obsessive-compulsive disorder.
Individual patients can be told only that the optimum dose of fluoxetine
for them will be the dose that produces the largest therapeutic effect with
the smallest side effect burden. Future studies should examine the
predictive utility of measures of serotonergic neuronal function and, if
plasma levels of norfluoxetine are examined, the use of chiral assays.
