SAFETY, TOLERABILITY AND EFFICACY OF THE REVERSIBLE MONOAMINE-OXIDASEINHIBITOR RS-8359 IN EARLY CLINICAL-TRIALS

The safety, tolerability and a preliminary assessment of the efficacy of the new reversible inhibitor of monoamine oxidase A, RS-8359, were evaluated in two studies in hospitalized, depressed patients. Daily do ses of 100 and 200 mg divided into two equal doses were compared with moclobemide at 300 mg/day divided into two equal doses. The results in dicated that all doses were safe with no evidence of significant chang es in laboratory values or cardiovascular parameters. There were no ap preciable changes in blood pressure or any evidence of orthostatic hyp otension. Tolerability was generally good, although the 200-mg daily d ose of RS-8359 and the 300-mg dose of moclobemide were both associated with a higher incidence of adverse events than the 100-mg daily dose of RS-8359. Initial titration of RS-8359 indicated that a slower escal ation of doses could ameliorate early adverse events and may improve t olerability of higher doses. However, most adverse events still occurr ed at the 200-mg daily dose of RS-8359. The efficacy of all active tre atments was similar, with no apparent advantage for the higher dose wh en the data were analysed on an intent-to-treat basis.