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Reply to Rosenblat, Smith & McIntyre

Article  in  Psychotherapy and Psychosomatics · May 2018

DOI: 10.1159/000488113

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 Letter to the Editor
Psychother Psychosom
DOI: 10.1159/000488113
Reply
Marta M. Maslej a Benjamin M. Bolker a Steven D. Hollon b
Benoit H. Mulsant c Paul W. Andrews a
a McMaster
University, Hamilton, ON, Canada; b Vanderbilt  
University, Nashville, TN, USA; c University of Toronto, Toronto,
ON, Canada
We are grateful for the interest shown by Rosenblat et al. [1] in
our meta-analysis [2]. They question its primary results: antide-
pressant (AD) use is associated with a 33% increased risk of death
in “general population” samples, while this risk is significantly
lower in “cardiovascular” samples. We do not believe that their
arguments are sound.
First, they argue that our findings are “not in accordance with
the FDA or APA depression treatment guidelines.” This is irrele-
vant to our aim of investigating the long-term safety of ADs.
They imply that we stratified the samples post hoc. As we dis-
cussed [2, pp. 269–270], our a priori decision to stratify was based
on our previous work [3]: (i) in addition to other physiological ef-
fects, many ADs have anti-clotting properties; (ii) this effect may
normalize clotting function in patients with hyperactivated pro-
aggregatory processes (e.g., many cardiovascular diseases); and
(iii) this effect may be harmful in people with otherwise normal
clotting processes.
Rosenblat et al. [1] also criticize our classification because of
our labelling. We agree that the “general population” label poses
interpretational challenges. However, we could not identify studies
that had specifically screened out individuals with pro-aggregato-
ry diseases. So, we included in this class studies involving commu-
nity samples, reasoning that although some individuals in these
studies might have pro-aggregatory diseases, most would not [2,
p. 278]. We believe “general population” is more suitable than other
labels that would definitely indicate the absence of cardiovascular
disease (e.g., “non-cardiovascular samples”). Since these studies
predominantly involved older adults, we suggested that “our find-
ings may not generalize to younger populations” [2, p. 278].
Similarly, they criticize our “cardiovascular” label because this
class included a sample with chronic obstructive pulmonary dis-
ease (COPD). As we discussed explicitly [2, p. 269], we used the
“cardiovascular” label to refer to conditions with elevated pro-ag-
gregatory processes, which is true of COPD [4, 5]. The view that
COPD and cardiovascular disease are separate conditions has been
© 2018 S. Karger AG, Basel
E-Mail karger@karger.com
www.karger.com/pps
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Received: March 4, 2018
Accepted: March 5, 2018
Published online: April 4, 2018
“firmly dispelled” by epidemiological, clinical, and experimental
evidence [6, p. 4]. Given our prediction, it would have been inap-
propriate to place the COPD sample in the “general population”
class. We also included one sample not ascertained for cardiovas-
cular illness into the “cardiovascular” class [7]. This sample had
high rates of smoking, obesity, and insulin resistance. Its average
Framingham risk score of 17 makes the average heart age about 20
years older than the average chronological age of 61 [8]. Thus, giv-
en these indicators of cardiovascular disease and hyperactivated
pro-aggregatory processes, this sample was placed in the “cardio-
vascular” class.
Finally, if they were correct and we made some errors in our
classification procedure (e.g., by including some individuals with
cardiovascular disease in the “general population” class or by in-
cluding some individuals without elevated pro-aggregatory pro-
cesses in the “cardiovascular” class), these errors would actually
work against our hypothesis and would have made it harder to
detect the differences we predicted a priori.
In summary, we believe that Rosenblat et al. [1] misunderstood
our paper in several ways and we stand by our conclusions.
References
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  2 Maslej MM, Bolker BM, Russell MJ, Eaton K, Durisko Z, Hollon SD,
Swanson GM, Thomson JA Jr, Mulsant BH, Andrews PW: The mortal-
ity and myocardial effects of antidepressants are moderated by preexist-
ing cardiovascular disease: a meta-analysis. Psychother Psychosom 2017;
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  3 Andrews PW, Thomson JA Jr, Amstadter A, Neale MC: Primum non
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Paul W. Andrews
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