COGNITIVE PERFORMANCE IN ELDERLY SUBJECTS AFTER A SINGLE-DOSE OF BEFLOXATONE, A NEW REVERSIBLE SELECTIVE MONOAMINE-OXIDASE-A INHIBITOR

Background: Patients with depression often have cognitive and psychomo tor performance impairments. Antidepressive treatments can correct the se deficits, provided sedative and anticholinergic adverse effects do not add to the preexisting condition, particularly in elderly patients . Newly developed antidepressants therefore should be without deleteri ous effects on cognitive functions, including memory. Befloxatone is a new antidepressant with a potent, selective, competitive, and reversi ble inhibitory activity on the A isoform of monoamine oxidase (MAO-A). Methods: The effects on cognition and psychomotor performance of sing le oral doses of befloxatone (10 mg) and amitriptyline (50 mg) were co mpared in a randomized, double-blind, placebo-controlled, three-way cr ossover design trial in 12 healthy elderly (65 to 85 years) volunteers . The performances of the subjects were evaluated by a comprehensive b attery of validated psychometric tests that explored alertness, psycho motor performance, information processing, and memory. Subjective feel ings on mood and sleep were rated on visual analog scales. MAO-A inhib ition was estimated by multiple titrations of 3,4-dihydrophenylglycol (DHPG) in plasma. Results: Amitriptyline displayed the expected delete rious effects on performance tasks, critical flicker fusion threshold, digit symbol substitution, and body sway and it deteriorated memory ( immediate and delayed free recall of words). In contrast, befloxatone did not impair cognition or psychomotor performance but instead signif icantly improved the delayed free recall. Amitriptyline adversely affe cted subjective feelings of alertness and contentedness, but befloxato ne permitted sustained alertness and did not alter other subjective fe elings or sleep. Concurrently, a single dose of 10 mg befloxatone mark edly decreased the DHPG concentration in plasma. Conclusion: Contrary to tricyclic antidepressants, whose deleterious effects are greater in elderly subjects, this study demonstrated the safety of befloxatone o n cognition and psychomotor performance in elderly subjects.