The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man.

The effects of single oral doses of bupropion, diazepam and the two combined, were examined in twelve (six male, six female) healthy volunteers, using a balanced cross over design and double-blind conditions. Results were analysed by analysis of variance and values of < 0.05 taken as significant. A significant reduction in signals detected in the Wilkinson vigilance test occurred after 5 mg diazepam and a similar trend occurred after 2.5 mg diazepam compared with lactose dummy. Performance after combination of bupropion 100 mg and diazepam 5 mg failed to differ from that after lactose. Bupropion alone never differed from lactose dummy. Calculation of the ratios of d' and β indicated that diazepam was reducing the subjects' ability to discriminate between signals and noise, rather than their willingness to report. Values of d' after combination of bupropion with diazepam did not differ from those after lactose. Subjective effects, measured using visual analogue scales, showed that the subjects rated themselves significantly more drowsy, muzzy and dreamy after both doses of diazepam than after lactose dummy. Combinations of bupropion 100 mg with diazepam 2.5 and 5 mg resulted in ratings which never differed from lactose on any dimension. Subjects were more bored after all treatments compared with lactose and this was the only dimension where bupropion produced a significant difference. Subjective effects had largely disappeared by 6 h. Tests of short term memory, reaction time and digit symbol substitution showed no significant effects, but errors in short term memory after diazepam approached significance ( = 0.092). Autonomic effects: no changes were seen in blood pressure (systolic or diastolic) and pupil diameter. Significant elevation of heart rate occurred after diazepam 2.5 mg, bupropion alone and in both combinations 6 h 15 min post-treatment. This probably resulted from a spuriously low value after lactose. EEG, quantitated using four filters approximating to the four clinical frequencies revealed no differences between active drug(s) and lactose at 2 h 45 min after treatment. A possible increase in fast activity occurred after bupropion 6 h 15 min post-treatment. It was concluded that bupropion 100 mg administered as a single dose, while not producing significant changes in the variables measured, when co-administered with single 5 mg doses of diazepam antagonised the functional impairment and drowsiness which follow that drug.