Safety, tolerability and efficacy of the reversible monoamine oxidase inhibitor 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 doses 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 indicated that all doses were safe with no evidence of significant changes in laboratory values or cardiovascular parameters. There were no appreciable changes in blood pressure or any evidence of orthostatic hypotension. Tolerability was generally good, although the 200-mg daily dose 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 escalation of doses could ameliorate early adverse events and may improve tolerability of higher doses. However, most adverse events still occurred at the 200-mg daily dose of RS-8359. The efficacy of all active treatments was similar, with no apparent advantage for the higher dose when the data were analysed on an intent-to-treat basis.