Dosulepin link with ischaemic heart disease
Patients who have taken the tricyclic antidepressant
dosulepin (dothiepin) are at increased risk of ischaemic heart disease,
a new study shows.
Dr Julia Hippisley-Cox, University of Nottingham,
and colleagues identified 933 patients, from nine general practices, who
had either been diagnosed with ischaemic heart disease (including angina
and myocardial infarction), had had coronary artery surgery, or who were
receiving repeat prescriptions for nitrates. The researchers matched 516
men to 3,081 male controls and 417 women to 2,435 female controls. The
risk of ischaemic heart disease was compared for different classes of
antidepressants and for individual antidepressants.
They found that patients who had ever taken dosulepin
had a raised odds ratio for ischaemic heart disease, even after adjustment
had been made for confounding factors such as diabetes, hypertension,
smoking and body mass index, and for taking other antidepressants. These
patients were found to be 67 per cent more likely to develop ischaemic
heart disease than matched controls.
The risk of ischaemic heart disease increased with
increasing maximum doses of dosulepin and with increasing numbers of prescriptions
for dosulepin, suggesting a dose-response relationship. No pattern was
found between time since last exposure and the risk of heart disease,
which, the researchers say, suggests that cardiotoxicity remains long
after treatment is stopped. The researchers also comment that “50 patients
would need to be treated with dosulepin for one year in order for one
to be harmed, assuming an incidence of ischaemic heart disease of 3 per
cent a year”.
No significant increase in the odds ratio for ischaemic
heart disease was identified for amitriptyline, lofepramine or for serotonin
reuptake inhibtors, after adjustments had been made for confounding factors
and for the use of other antidepressants (BMJ 2001;323:666).
David Taylor, chief pharmacist at the Maudsley Hospital,
London, told The Journal that the study was important because rather
than just identifying a link between dosulepin and ischaemic heart disease
a dose-response relationship was seen. He commented that people with depression
had a higher rate of mortality than those who did not but it was not known
whether this was because of the use of antidepressants.
He added that it took a long time to learn everything
about a drug. Identifying a link between dosulepin and ischaemic heart
disease serves as an alert that drugs can have important new effects even
when used for a number of years, he said.
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