19F magnetic resonance spectroscopy study of fluvoxamine

Magnetic resonance spectroscopy (MRS) provides a noninvasive tool for studying the concentration, distribution, and binding properties of fluorinated psychoactive compounds in the human brain. Selective serotonin reuptake inhibitors (SSRIs) are a widely prescribed class of psychiatric drugs for a range of illnesses including depression, panic and obsessive compulsive disorder (OCD). Fluvoxamine is a recently FDA approved SSRI for the treatment of OCD and is particularly well suited to investigation by MRS because it contains three chemically identical fluorine atoms. 19F MRS offers the advantages of high sensitivity compared to other nuclei and no endogenous background signal, allowing the detection of compounds at tissue levels not visible with other nuclei. We prospectively studied 8 subjects entered into treatment with fluvoxamine for OCD at the Outpatient Psychiatry Clinic at the University of Washington. Subjects were scanned 12 hours following an acute loading dose of 100 mg fluvoxamine and then serially over 3 to 6 months to determine the concentration of the drug before and during brain steady-state. In addition, spin-lattice relaxation times were determined by inversion recovery technique for each subject and localized brain maps were made for 2 subjects using standard spectroscopic imaging techniques. Treatment response was monitored clinically using the Y-BOCS scale. Preliminary results indicate that brain steady-state concentrations are reached within 30 days after being at a consistent dose of fluvoxamine. There is some variability between subjects on the dose to steady-stated concentration relationship. This suggests possible differences in nonspecific protein and membrane binding of fluvoxamine or a difference in the metabolism of the drug. Blood levels of the drug to compare with brain levels are pending. We have preliminary evidence from spin-lattice relaxation studies that the binding characteristics of the drug do vary between subjects. This may have consequences for understanding differences in treatment response between patient populations.