MOCLOBEMIDE AND FLUVOXAMINE COADMINISTRATION - A PROSPECTIVE-STUDY INHEALTHY-VOLUNTEERS TO INVESTIGATE THE POTENTIAL DEVELOPMENT OF THE SEROTONIN SYNDROME

The combination of serotonin re-uptake inhibitors and classical inhibi tors of monoamine oxidase (MAO) has been associated with the severe ad verse effects of the so-called 'serotonin syndrome'. In the present st udy 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. Ascend ing doses of moclobemide or placebo were added to a steady state dosin g regimen of fluvoxamine. The highest incidence of adverse events occu rred in the run-in phase. Three subjects were withdrawn when treated w ith fluvoxamine alone. In the 13 volunteers receiving the active combi nation tiredness, dizziness and headache were more frequently noted th an in the nine controls receiving fluvoxamine and placebo. The types o f adverse events observed before and after the addition of moclobemide to fluvoxamine were very similar. Fluvoxamine plasma concentrations r emained unchanged over the period of moclobemide co-administration. Pl asma concentrations of moclobemide were slightly higher than those obs erved in previous studies. In conclusion, the combined administration of fluvoxamine and moclobemide did not precipitate symptoms of the 'se rotonin syndrome'. This is of particular relevance for the therapeutic practice if switching of the antidepressant medication is necessary.