VENLAFAXINES EFFECTS ON HEALTHY-VOLUNTEERS DRIVING, PSYCHOMOTOR, AND VIGILANCE PERFORMANCE DURING 15-DAY FIXED AND INCREMENTAL DOSING REGIMENS

Effects of venlafaxine, an antidepressant acting by selective serotoni n and norepinephrine reuptake inhibition with a potency ratio of 5:1, were assessed in a standardized, actual driving test, a battery of psy chomotor tests (Critical Flicker/Fusion Frequency, Critical Tracking, Divided Attention), and a 45-minute vigilance test (Mackworth Clock). Thirty-seven healthy volunteers, 22 of whom completed the study, recei ved venlafaxine in fixed (37.5 mg twice a day) and incremental (37.5-7 5 mg twice a day) doses as well as mianserin (10-20 mg three times a d ay) and placebo according to a 4-period (15 days each), double-blind, crossover design. Testing occurred on days 1 and 7 and after dose incr ements, on days 8 and 15. Plasma concentrations of venlafaxine and its active metabolite were measured on test days for con firming complian ce. Venlafaxine had no significant effect on the primary driving param eter (standard deviation of lateral position) and failed to impair psy chomotor performance. Mianserin profoundly and consistently impaired d riving and psychomotor performance. However, both drugs significantly impaired vigilance performance. Maximal effects occurred on day 1 with mianserin and similarly on day 7 with venlafaxine in both series. The increment in venlafaxine's dose on day 8 did not increase this effect . The drug's selectively impairing effect on vigilance is shared by ot her ''serotonergic'' anxiolytics and antidepressants, suggesting that interference with 5-HT transmission reduces arousal in particularly mo notonous tasks or environments. This study concludes that venlafaxine does not generally affect driving ability and should be safe for use b y patients who drive.