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Pharmacopsychiatry 2011; 44(07): 317-323
DOI: 10.1055/s-0031-1284426
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Augmentative Effects of Fluvoxamine on Duloxetine Plasma Levels in Depressed Patients

M. Paulzen
1   Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany
2   JARA – Translational Brain Medicine
,
A. Finkelmeyer
3   The Institute of Neuroscience, Newcastle University, Newcastle, England, UK
,
M. Grözinger
1   Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany
2   JARA – Translational Brain Medicine
› Author Affiliations
Further Information

Publication History

received 17 February 2011
revised 22 June 2011

accepted 24 June 2011

Publication Date:
06 October 2011 (online)

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Abstract

Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine reuptake with weak activity on dopamine reuptake. Enzymes involved in duloxetine metabolism are cytochrome P450 isoenzymes (CYP) CYP1A2 and to a lesser extent CYP2D6 whereas the selective serotonin reuptake inhibitor Fluvoxamine is known to be a potent inhibitor of CYP1A2. Changes in plasma levels of duloxetine revealing pharmacokinetic interactions with fluvoxamine, clinical effects and adverse effects of adding fluvoxamine in thirteen patients with a steady-state duloxetine treatment by intraindividual comparisons were analyzed in this retrospective survey. Patients had been treated with duloxetine under steady-state conditions until fluvoxamine was added. Plasma duloxetine levels were measured at steady state of different daily doses due to lacking experience with the combination of DLX and FLX. Adding 25 mg of fluvoxamine (FLX) per day to a steady-state treatment with 30 mg of duloxetine (DLX) in 8 patients led to an average increase of duloxetine plasma levels that was 3-fold with a magnitude of 50–506%. Our findings indicate that duloxetine plasma levels can be enhanced by a potent CYP1A2 inhibition by FLX and that DLX, even in higher plasma levels, seems to be well tolerated. The use of combined treatments, however, underscores the importance of understanding pharmacokinetic interactions.

Key words

duloxetine - fluvoxamine - plasma level - interaction - CYP1A2 - TDM - depression
 

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