The effects of nefazodone, imipramine and placebo, alone and combined with alcohol, in normal subjects.

Nefazodone (200 mg, 400 mg/day) imipramine (150 mg/day) and placebo were administered to 12 normal, healthy volunteer subjects for a period of 8 days each. A measured dose of alcohol was consumed with the drug on day 8. A battery of physiological, psychomotor, cognitive and subjective tests was carried out before drug administration and 2 h after drug administration on days 1, 7, and 8. Nefazodone had little effect on heart rate and blood pressure whereas imipramine increased both heart rate and diastolic blood pressure. Nefazodone 400 mg impaired the critical flicker fusion threshold. Dose-dependent improvements in psychomotor performance (Gibson Spiral Maze) and complex memory performance (learning, pursuit rotor, and visual working memory) were produced by nefazodone while imipramine administration impaired performance on these tasks. Subjective changes in alertness and bodily symptoms were produced by all active compounds. While nefazodone failed to potentiate the sedative-hypnotic (depressant) effects of alcohol, imipramine tended to enhance them for psychomotor performance, memory assessments, and some subjective ratings. Thus, nefazodone, particularly at lower dose levels, causes less disruption of human performance than imipramine. This effect probably reflects the lack of anticholinergic activity of nefazodone. Also, nefazodone failed to potentiate the depressant effects of alcohol, perhaps because of its minimal alpha-blockade.