Hippisley-Cox and colleagues reported1 previous use of the
antidepressant dosulepin (dothiepin) is associated with increased ischemic
heart disease (IHD) and suggested the relationship may be causal. However,
we believe there are good reasons for a different interpretation.
The
unadjusted odds ratios in table 2 run from 1.28 to 1.73 for all types of
antidepressants as well as for those receiving no antidepressant
treatment. Taken together, an alternative interpretation is that it is
depression itself, rather than antidepressant use, that is the main factor
driving the subsequent increase in IHD. The apparent specificity for
dosulpin might well be, as the authors suggest, due to its more frequent
use in more severe depression. There have been a large number of
prospective studies demonstrating depression to be an independent risk
factor for the subsequent development of IHD and the relative risk in
these studies is higher than that found in the report by Hippisley-Cox,
e.g. 4.5 by Pratt et al 19962 and 2.1 by Ford et al 19963. These studies
also found a dose-response relationship between the severity of depression
and the risk of IHD. This would be consistent with the view that it is
depression itself that is a risk factor for IHD and that dosulpin (and
other antidepressants) may not have any direct effects.
Furthermore, there
are a number of potential biological mechanisms by which depression could
either lead to or exacerbate IHD. For example, depression has robust
associations with abnormalities in platelet activity and raised levels of
proinflammatory cytokines4 which would increase the atherogenic process.
Such mechanisms have a greater biological plausibility for explaining an
increase in IHD than those mentioned in the report to try and explain the
association with dosulpin, which are more relevant to increasing
arrhythmias and sudden cardiac death.
Department of Psychiatry,
University of Newcastle upon Tyne,
Wolfson Research Centre,
Newcastle General Hospital
NE4 6BE
We are not aware of any competing interests.
1. Hippisley-Cox J, Pringle M, Hammersley V, Crown N, Wynn A, Meal A,
et al. Antidepressants as risk factor for ischemic heart disease: case-
control study in primary care. BMJ 2001;323:666-9.
2. Pratt LA, Ford DE, Crum RM, Armenian HK, Gallo JJ, Eaton WW.
Depression, psychotropic medication, and risk of myocardial infarction.
Prospective data from the Baltimore ECA follow-up. Circulation
1996;94(12):3123-9.
3. Ford DE, Mead LA, Chang PP, Cooper-Patrick L, Wang NY, Klag MJ.
Depression is a risk factor for coronary artery disease in men: the
precursors study. Archives of Internal Medicine 1998;158(13):1422-6.
4. Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to
cardiovascular disease: epidemiology, biology, and treatment. Archives of
General Psychiatry 1998;55(7):580-92.
Competing interests:
No competing interests
30 October 2001
Alan Thomas
Lecturer in Old Age Psychiatry
Wolfson Research Centre, Newcastle General Hospital,University of Newcastle upon Tyne
Rapid Response:
Depression not Dosulpin increases IHD
The Editor
Hippisley-Cox and colleagues reported1 previous use of the
antidepressant dosulepin (dothiepin) is associated with increased ischemic
heart disease (IHD) and suggested the relationship may be causal. However,
we believe there are good reasons for a different interpretation.
The
unadjusted odds ratios in table 2 run from 1.28 to 1.73 for all types of
antidepressants as well as for those receiving no antidepressant
treatment. Taken together, an alternative interpretation is that it is
depression itself, rather than antidepressant use, that is the main factor
driving the subsequent increase in IHD. The apparent specificity for
dosulpin might well be, as the authors suggest, due to its more frequent
use in more severe depression. There have been a large number of
prospective studies demonstrating depression to be an independent risk
factor for the subsequent development of IHD and the relative risk in
these studies is higher than that found in the report by Hippisley-Cox,
e.g. 4.5 by Pratt et al 19962 and 2.1 by Ford et al 19963. These studies
also found a dose-response relationship between the severity of depression
and the risk of IHD. This would be consistent with the view that it is
depression itself that is a risk factor for IHD and that dosulpin (and
other antidepressants) may not have any direct effects.
Furthermore, there
are a number of potential biological mechanisms by which depression could
either lead to or exacerbate IHD. For example, depression has robust
associations with abnormalities in platelet activity and raised levels of
proinflammatory cytokines4 which would increase the atherogenic process.
Such mechanisms have a greater biological plausibility for explaining an
increase in IHD than those mentioned in the report to try and explain the
association with dosulpin, which are more relevant to increasing
arrhythmias and sudden cardiac death.
Dr A.J.Thomas
Lecturer in Old Age Psychiatry
a.j.Thomas@ncl.ac.uk
Prof J.T.O'Brien
Professor of Old Age Psychiatry
j.t.o'brien@ncl.ac.uk
Department of Psychiatry,
University of Newcastle upon Tyne,
Wolfson Research Centre,
Newcastle General Hospital
NE4 6BE
We are not aware of any competing interests.
1. Hippisley-Cox J, Pringle M, Hammersley V, Crown N, Wynn A, Meal A,
et al. Antidepressants as risk factor for ischemic heart disease: case-
control study in primary care. BMJ 2001;323:666-9.
2. Pratt LA, Ford DE, Crum RM, Armenian HK, Gallo JJ, Eaton WW.
Depression, psychotropic medication, and risk of myocardial infarction.
Prospective data from the Baltimore ECA follow-up. Circulation
1996;94(12):3123-9.
3. Ford DE, Mead LA, Chang PP, Cooper-Patrick L, Wang NY, Klag MJ.
Depression is a risk factor for coronary artery disease in men: the
precursors study. Archives of Internal Medicine 1998;158(13):1422-6.
4. Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to
cardiovascular disease: epidemiology, biology, and treatment. Archives of
General Psychiatry 1998;55(7):580-92.
Competing interests: No competing interests