Antidepressants do not increase the lethality of ketamine in mice.

Swiss-Webster mice were allocated to 35 groups of 20 each, including controls, to evaluate the effect of pretreatment with antidepressant drugs on the LD50 of ketamine i.p. Deaths occurred only in groups given ketamine 400 or 600 mg kg-1. Within these groups, there were no consistent differences among untreated mice and those given one of three daily doses of either a tricyclic (amitriptyline) or monoamine oxidase inhibitor (tranylcypromine) antidepressant in their drinking water for 19 days before the ketamine injections. The ketamine LD50 values for the three major pretreatment groups were: controls 400 mg kg-1; amitriptyline 478 mg kg-1; tranylcypromine 483 mg kg-1. Although non-fatal additive toxicity is not ruled out by these findings, mortality from ketamine was not increased by pretreatment with either type of antidepressant.