The combination of classic monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressant drugs (TCAs) has been associated with a variety of adverse events.A switch in treatment from TCAs to moclobemide, a reversible and selective inhibitor of MAO-A, was investigated in a double-blind, placebo-controlled study in healthy volunteers. Two groups of 12 subjects were treated with either amitriptyline (75 mg/day) or clomipramine (100 mg/day) until steady-state conditions had been attained (14 days). Treatment with the TCAs was discontinued abruptly and switched to either a therapeutic dose regimen of moclobemide (300 mg/day) or placebo. The tolerability and safety pattern did not reveal any clinically relevant differences between moclobemide and placebo recipients, nor was there any sign of a pharmacokinetic interaction between the TCAs and moclobemide. In conclusion, the findings of this study suggest that therapeutic doses of moclobemide up to 300 mg daily can be given 24 hours after the last dose of treatment with either amitriptyline or clomipramine without major risks. (J Clin Psychopharmacol 1995;15:41-48).