Why do fatal overdose rates vary between antidepressants?

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Abstract
Age specific death rates for poisoning with different antidepressant drugs, based on mortality statistics and the numbers of prescriptions dispensed, were calculated for England and Wales 1979-1985. There are marked variations in mortality associated with different drugs; the highest rates are found with amitriptyline and dothiepin whereas the lowest were associated with mianserin and clomipramine. For all drugs considered, the calculated mortality rates for the over 65 year olds, though still substantial, were lower than those in patients under 65 years of age, probably because of a diminished detection rate of poisoning in this older age group. A high proportion of the fatal overdoses implicating amitriptyline and dothiepin involved more than one substance. The rank order of mortality rates from antidepressants was identical in the different age groups. The implications of these findings are discussed. It is concluded that the variations in mortality rates are mostly due to variations in the inherent toxicity of the drugs (particularly their cardiovascular effects) and only in part due to possible differences in compliance. It is suggested that when antidepressant drugs are prescribed, the risk of death from overdose should be taken into account. Tricyclic drugs, particularly amitriptyline, dothiepin, doxepin, trimipramine and maprotiline, should be avoided in patients at risk of suicide, whatever the age of the patient.