Am J Psychiatry 1997; 154:516-522
Copyright © 1997 by American Psychiatric Association
19F magnetic resonance spectroscopy investigation in vivo of acute and steady-state brain fluvoxamine levels in obsessive-compulsive disorder
WL Strauss, ME Layton, CE Hayes and SR Dager
Diagnostic Imaging Sciences Center, University of Washington School of Medicine, Seattle 98105-6099, USA.
OBJECTIVE: The purpose of this study was to investigate the
pharmacokinetics of fluvoxamine in the human brain by using fluorine-19
magnetic resonance spectroscopy (19F MRS) and to assess the relationships
among fluvoxamine brain levels, fluvoxamine plasma levels, and clinical
efficacy. METHOD: Eight subjects with DSM-IV obsessive-compulsive disorder
were entered into a prospective, open- label treatment trial of
fluvoxamine. 19F MRS measurements of whole brain drug and metabolite
concentrations and spin-lattice (T1) relaxation times were performed
serially in seven subjects for up to 5 months. A psychiatric determination
of clinical response and a blood sample for plasma fluvoxamine measurement
were obtained at each 19F MRS session. RESULTS: The subjects achieved
steady-state brain concentrations of fluvoxamine within 30 days after
consistent daily dosing, as determined by stabilization of brain
fluvoxamine concentrations. The mean brain-to-plasma ratio at steady state
was 24 to 1. Brain fluvoxamine T1 values from 140 to 230 msec were
observed. All but one subject experienced substantial improvement in
symptoms. The one nonresponder exhibited several-fold higher plasma and
brain fluvoxamine levels. CONCLUSIONS: Brain fluvoxamine levels were
substantially higher than plasma levels. Steady-state brain levels
correlated to plasma levels but not to dose. Systematic assessment of
treatment response in relation to brain or plasma fluvoxamine level was not
feasible because of the marked and rapid clinical response during
open-label treatment. These data suggest that fluvoxamine attains brain
steady-state levels substantially faster than fluoxetine, with
corresponding clinical implications.
