Background. The prescription of antidepressants has increased substantially over the last 10 years. It is therefore timely to examine trends in mortality associated with overdoses of antidepressants and to compare the relative mortality associated with different antidepressants.

Methods. Data were derived from a newly developed national database of deaths from overdose and poisoning in England and Wales between 1993 and 1997. Age and sex specific death rates associated with overdose and poisoning with antidepressants were calculated together with numbers of deaths per 100000 prescriptions of individual antidepressants.

Results. Twenty per cent (2503) of all deaths from overdose or poisoning were antidepressant related. The number of deaths increased by 18% between 1993 and 1997. Ninety-five per cent of deaths from antidepressants were associated with tricyclic antidepressants, particularly dothiepin and amitriptyline. Tricyclic antidepressants were associated with 5·3 deaths per 100000 prescriptions, 4·4 for monoamine oxidase inhibitors and 0·4 for selective serotonin reuptake inhibitors. Annual death rates were highest in men aged 30–44 years (18·2 per million) and women aged 45–59 years (14·8). Death rates from antidepressants were 2·5 times higher in the most deprived fifth than in the least deprived fifth of enumeration districts.

Conclusions. Antidepressants are an important cause of death from poisoning and overdose. SSRIs and newer antidepressants are associated with <10% of the risk of death than the older antidepressants. There is a strong association between area deprivation and deaths from antidepressants.