The Toxicity of Antidepressants in Overdose: Incidence and Mechanisms

Abstract

There are wide variations in the incidence of fatal overdoses with different antidepressants. Older tricyclic drugs such as amitriptyline and dothiepin have a higher incidence of fatality than newer atypical drugs like mianserin, whatever the age of the patient. Differences in incidence arise principally from variations in inherent toxicity and only partly from a combination of variable patient compliance and selective prescription. Inherent toxicity is mainly cardiovascular in nature, and those antidepressants with pronounced quinidine-like and atropine-like effects tend to be the most toxic in overdose. Evidence is emerging that some antidepressants, particularly selective inhibitors of 5-HT reuptake and, for different reasons, the new tricyclic lofepramine, may reduce the risk of fatal overdosage.