Venlafaxine's Effects on Healthy Volunteers' Driving, Psychomotor, and Vigilance Performance During 15-Day Fixed and Incremental Dosing Regimens

Abstract

Effects of venlafaxine, an antidepressant acting by selective serotonin and norepinephrine reuptake inhibition with a potency ratio of 5:1, were assessed in a standardized, actual driving test, a battery of psychomotor 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, received venlafaxine in fixed (37.5 mg twice a day) and incremental (37.5-75 mg twice a day) doses as well as mianserin (10-20 mg three times a day) and placebo according to a 4-period (15 days each), double-blind, crossover design. Testing occurred on days 1 and 7 and after dose increments, on days 8 and 15. Plasma concentrations of venlafaxine and its active metabolite were measured on test days for confirming compliance. Venlafaxine had no significant effect on the primary driving parameter (standard deviation of lateral position) and failed to impair psychomotor performance. Mianserin profoundly and consistently impaired driving 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 other "serotonergic" anxiolytics and antidepressants, suggesting that interference with 5-HT transmission reduces arousal in particularly monotonous tasks or environments. This study concludes that venlafaxine does not generally affect driving ability and should be safe for use by patients who drive.

Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic

“…Until this evidence becomes available, selective serotonin reuptake inhibitors and nonbenzodiazepine drugs are recommended as first-choice treatment regarding driving safety. For example, the nonbenzodiazepine hypnotic zaleplon 37,39 and antidepressants such as fluoxetine, paroxetine, and venlafaxine 38,40 have been shown not to impair driving ability.…”

Cognitive function is related to fronto-striatal serotonin transporter levels – a brain PET study in young healthy subjects

“…Conversely for attention, ATD has in some studies (Booij et al 2005;Schmitt et al 2000) although not in all Sobczak et al 2002) been reported to improve performance in the Stroop Color Word Test (Jensen and Rohwer 1966), a test that relies heavily on focused attention. In line, serotonergic stimulation with SSRIs reduces sustained attention (Ramaekers et al 1995;O'Hanlon et al 1998;Schmitt et al 2002). These pharmacological manipulations of the serotonergic system are generally unspecific and affect many of the subtypes of pre-and postsynaptic serotonin receptors as well as the serotonin transporter (SERT), although in vivo studies using [ 11 C]DASB binding after ATD have failed to find significant changes in SERT binding (Praschak-Rieder et al 2005;Milak et al 2005).…”

Effects of Medicinal Drugs on Fitness to Drive

“…In acute doses, mianserine caused driving impairment comparable to the effects of a BAC of 1.0 g/L (Louwerens and Brookhuis 1984; Ramaekers et al 1992a;O'Hanlon et al 1998). After 1 and 2 weeks of treatment, the driving impairment was less but still significantly worse than placebo and was comparable to a BAC of more than 0.5 g/L .…”