Lack of interaction between amisulpride and lorazepam on psychomotor performance and memory in healthy volunteers

The potential pharmacodynamic interaction between amisulpride (a benzamide-type antipsychotic) and lorazepam was evaluated in a randomized, double-blind, cross-over, placebo-controlled study involving 18 healthy caucasian male volunteers, aged 18-35 years. They received single doses of amisulpride 50 mg and 200 mg. The interaction of the drug with a single oral dose of lorazepam 2 mg was assessed on six 1-day treatment periods separated by washout periods of 1 week. Pharmacodynamic criteria were: critical flicker fusion frequency, multiple choice reaction time, tapping, body sway, arithmetic calculation, Buschke's test for short and long term memory and self-ratings by ARCI scale. Prolactin as assayed for each treatment period. Statistical analysis was performed using a 3-way ANOVA. For psychometric tests and body sway, analyses were evaluated on changes from baseline. For memory test, analyses were done on raw data. Amisulpride alone, at single oral dose of 50 mg and 200 mg, was devoid of any clinically relevant impairment psychometric tests, short term and long term memory and mood. A single oral dose of lorazepam 2 mg induced marked impairment in psychometric performances, which all, except CFF test, were severely affected. Disturbances were also recorded in memory tests, and in subjective sensation (ARCI). The peak effects were 2-4 h after administration, but the majority of results were also affected up to 8 h. Prolactin levels were increased after either dose of amisulpride, but not after placebo or lorazepam. The co-administration of amisulpride plus lorazepam induced a prolactin elevation equivalent to that of amisulpride alone. In conclusion, the coadministration of amisulpride, at both doses of 50 mg and 200 mg, did not potentiate nor antagonize the detrimental effect of lorazepam 2 mg on pharmacodynamic parameters. (C) 1998 John Wiley & Sons, Ltd.