Augmentative Effects of Fluvoxamine on Duloxetine Plasma Levels in Depressed Patients
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.
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ABSTRACT: Introduction: Fluvoxamine is one of the most widely prescribed antidepressants and presents data from 30 years of clinical experience. Areas covered: The present review article describes the pharmacokinetic properties of fluvoxamine and their implications for the treatment of anxiety disorders (AD). A search in the main database sources (Medline, Isi Web of Knowledge and Medscape) has been performed in order to obtain a comprehensive and balanced evaluation of fluvoxamine about the implications of its pharmacokinetic properties for the treatment of AD. The word 'fluvoxamine' has been associated with 'pharmacokinetics', 'interactions', 'generalized anxiety disorder', 'social anxiety disorder', 'social phobia', 'panic disorder', 'anxiety' and 'tolerability'. No restriction criteria were established in relation to methodology or year of publication. Only English-language articles have been selected. Expert opinion: Fluvoxamine presents high tolerability and safety so that it can be considered as a therapeutic option in case of panic disorder and social anxiety disorder. In contrast, its weakness is in extended interaction with CYP450 enzymatic system that may limit its use in elderly or patients with medical comorbidities. Finally, data of efficacy about generalized anxiety disorder are very limited and preliminary so that it is not possible to draw any sound conclusions.Expert Opinion on Drug Metabolism & Toxicology 03/2015; 11(4):1-12. DOI:10.1517/17425255.2015.1021331 · 2.93 Impact Factor