BRAIN ELIMINATION HALF-LIFE OF FLUVOXAMINE MEASURED BY F-19 MAGNETIC-RESONANCE SPECTROSCOPY

Objective: This study used fluorine-19 magnetic resonance spectroscopy (F-19 MRS) to characterize the elimination of fluvoxamine from the hu man brain after abrupt drug discontinuation. The elimination half-live s of fluvoxamine in brain and plasma were determined to assess their i nterdependence and the relationship of brain half-life to the clinical practice of drug holidays and reports of acute withdrawal symptoms. M ethod: Six subjects completing clinical treatment with fluvoxamine wer e enrolled in the study. Spectroscopic quantification of whole brain f luvoxamine concentrations and chromatographic determination of plasma fluvoxamine levels were performed serially for up to 10 days after dru g withdrawal. Psychiatric evaluation to assess withdrawal symptoms was also done at each scanning session. Results: Elimination of fluvoxami ne in the brain and plasma was optimally described by first-order kine tics; the mean elimination half-lifes were 58 hours and 26 hours, resp ectively. The mean ratio of fluvoxamine brain elimination half-life to plasma half-life was 2.4. Three of the six subjects experienced mild to moderate withdrawal symptoms between the third and fifth days of th e study, which corresponded to between one and two brain half-lives of fluvoxamine. Conclusions: The brain elimination half-life for fluorin ated psychotropic compounds can be measured noninvasively by F-19 MRS. The elimination half-life of fluvoxamine was found to be substantiall y longer for the brain than for plasma. The time course of withdrawal symptom onset and the rationale for drug holidays with fluvoxamine app ear to be well explained by the brain elimination half-life.