Moclobemide and fluvoxamine co‐administration: A prospective study in healty volunteers to investigate the potential development of the ‘serotonin syndrome’

Abstract The combination of serotonin re‐uptake inhibitors and classical inhibitors of monoamine oxidase (MAO) has been associated with the severe adverse effects of the so‐called ‘serotonin syndrome’. In the present study the combined administration of moclobemide, a novel, selective and reversible inhibitor of MAO‐A and fluvoxamine, a selective serotonin re‐uptake inhibitor, was studied in 25 healthy male volunteers. Ascending doses of moclobemide or placebo were added to a steady state dosing regimen of fluvoxamine. The highest incidence of adverse events occurred in the run‐in phase. Three subjects were withdrawn when treated with fluvoxamine alone. In the 13 volunteers receiving the active combination tiredness, dizziness and headache were more frequently noted than in the nine controls receiving fluvoxamine and placebo. The types of adverse events observed before and after the addition of moclobemide to fluvoxamine were very similar. Fluvoxamine plasma concentrations remained unchanged over the period of moclobemide co‐administration. Plasma concentrations of moclobemide were slightly higher than those observed in previous studies. In conclusion, the combined administration of fluvoxamine and moclobemide did not precipitate symptoms of the ‘serotonin syndrome’. This is of particular relevance for the therapeutic practice if switching of the antidepressant medication is necessary.