Heart attack victims in Ontario were twice as likely to be treated with
antidepressants in 2002 as they were in 1993, but so was a group of matched
controls, a pattern reflecting general population trends rather than an
increased concern about depression in cardiac patients, according to a study
of more than 137,000 elderly Ontario residents.
Moreover, although the use of selective serotonin uptake inhibitors (SSRIs)
increased as a percentage of prescriptions, the percentage of patients taking
tricyclic antidepressants (TCAs) remained the same.
"Despite the higher rates of SSRI prescribing on a population basis,
we don't see that evidence demonstrating a strong connection between
depression and reinfarcts and deaths among MI patients is yet translating into
clinical practice," said lead author Nili Benazon, Ph.D., of the Centre
for Addiction and Mental Health and the Sunnybrook and Women's Health Sciences
Centre in Toronto, in an interview with Psychiatric News.
Prior epidemiological research has found a strong association between
depression and heart disease, but the issue of causality remains unconfirmed
by prospective studies (Psychiatric News, August 5, 2005).
Benazon and her colleagues, Muhammad Mamdani, Pharm.D., of Toronto's
Institute of Clinical Evaluative Sciences, and James Coyne, Ph.D., of the
University of Pennsylvania Health System in Philadelphia, drew on four
databases for the study: provincial prescription claims, health insurance, and
a population registry, as well as the Canadian Institutes of Health
Information's hospital discharge abstract database. The study was published in
the November-December 2005 Psychosomatic Medicine.
The researchers identified 68,870 patients who had had heart attacks and an
equal number of age- and sex-matched controls. Antidepresssants in the study
included tricyclic and heterocyclic antidepressants, monoamine oxidase
inhibitors, and SSRIs.
The percentage of heart attack patients getting antidepressants edged
upward consistently over the study period, going from 7.8 percent (n=128 of
1,637 subjects) in 1993 to 15.7 percent (350/2,231) in 2002, and in matched
control patients who had not had a heart attack, increasing from 6.4 percent
(105/1,637) to 12.2 percent (273/2,231).
The initial results of the study showed that post-MI patients were more
likely than controls to be prescribed an antidepressant (odds ratio=1.34).
However, adjusting for the number of prescriptions for any medications
paradoxically shifted that relationship, so that those who had had heart
attacks were actually less likely to receive antidepressants than matched
controls (odds ratio=0.81).
Why would having more prescriptions reduce the chances of being prescribed
Drawing on previous research by others, Benazon and colleagues suggested
that the total number of prescriptions reflects medical comorbidity or
physician visits, and that management of a chronic disease interferes with
treatment of unrelated conditions.
"It is therefore plausible that the likelihood that an elderly
post-MI patient will receive a prescription for an antidepressant increases
with the number of medical visits, but the competing demands of managing the
cardiac condition decrease the likelihood that antidepressants will be
prescribed in a given visit," they wrote. "Health care following
an MI might thus be characterized by more visits but less likelihood of a
prescription for an antidepressant in any given visit, yielding the contrast
between higher unadjusted odds of receiving an antidepressant and lower
In short, patients who had heart attacks were prescribed more medications
but relatively fewer of those prescriptions were for antidepressants.
The study results also reflected the increasing availability and use of
SSRIs. In 1993, 23 percent of all antidepressant prescriptions for post-MI
patients were for SSRIs, rising to 62 percent in 2002. Prescriptions for TCAs
fell over the same time, from 83 percent to 36 percent. (A small number of
patients received heterocyclic antidepressants or monoamine oxidase
Despite this general reversal in percentage of prescriptions, there was no
corresponding drop in the percentage of patients prescribed TCAs. Six percent
of post-MI patients and 5 percent of controls got TCAs in 1993, figures that
were unchanged in 2002 and left the researchers puzzled.
"That there has been no reduction in the proportion of patients
receiving TCAs over the last decade suggests that there is a problem in
continued prescription for depression, and presumably at cardiotoxic dosages,
but we cannot establish the magnitude of the problem," the authors
"The difficulty in unambiguously interpreting the TCA data is that
some represent low dosage for pain and sleep," added Benazon."
Also, our first observations in this dataset were from a decade
earlier, when there was less evidence about toxicity and fewer alternatives to
"I would agree that SSRIs are safer, but that information may not be
well known to physicians unless it's publicized or included in
guidelines," said David Sheps, M.D., editor of Psychosomatic
Medicine and a professor of medicine and associate director of the
division of cardiovascular medicine at the University of Florida."
People have a hard time changing their prescribing habits. But at least
we see a gradual rise in the percentage of patients getting antidepressants.
That's probably a good thing."
The growing suspicion of excessive and inappropriate prescription of
antidepressants, even in the face of persistent under-treatment and inadequate
treatment of depression, also concerned the researchers, said Benazon.
She cited unpublished data indicating that at least 25 percent of primary
care patients receiving antidepressants for depression had never experienced
two consecutive weeks of mood disturbance.
The bulk of treatment with antidepressants occurs in general medical rather
than specialty mental health care, and only 20 percent to 30 percent of
patients receiving treatment for depression in general medical care obtain
adequate care, she said.
"Questions of the specificity and adequacy of treatment being
provided for depression are important in evaluating the progressive increase
in the prescription of antidepressants to post-MI patients and elderly
patients more generally, but answering these questions requires going beyond
the data available in our integrated dataset."
"Trends in the Prescribing of Antidepressants Following Acute
Myocardial Infarction, 1993-2002" is posted at<www.psychosomaticmedicine.org/cgi/content/full/67/6/916>.▪