Opinion
EDITORIAL
Depression After Stroke—Frequency, Risk Factors,
and Mortality Outcomes
Craig S. Anderson, MD, PhD
Funders and leaders of health and social services are increas-
ingly seeking evidence-based solutions to help address de-
mands brought about by demographic shifts, high preva-
lence of chronic diseases, and
economic constraints affect-
Related article ing populations and systems
of care. Reliable data on the
efficacy and cost-effectiveness of therapies and treatment strat-
egies derived from randomized clinical trials are assuming
greater priority (and a peer-review preference) for funding bod-
ies of clinical research rather than simply (further) describing
the burden of a condition or situation. Yet, the latter research
is central to our understanding of the patterns and risks of
health conditions and in designing and testing intervention
strategies. The article by Jørgensen et al1 is therefore an im-
portant reminder of the value of conventional “shoe leather”
analytical epidemiology in providing a seminal appraisal of the
well-recognized but poorly understood and treated disorder
of stroke-associated depression.
Using data linkage across several nationwide registries in
Denmark, these researchers were able to ascertain all cases of
new-onset depression during 2 years of follow-up in 157 243
first-time hospitalized patients with acute stroke or transient
ischemic attack (TIA) who were matched according to age,
sex, and area of residence with 160 230 healthy control indi-
viduals over a 10-year period between 2001 and 2011.
Depression was defined according to a diagnosis reported
through medical record coding, a death certificate, or any
prescription for antidepressant medication. Overall, one-
quarter of the patients with stroke/TIA vs nearly 10% of the
reference population experienced depression during 2 years
from study entry. Compared with the reference population,
the rate of depression in patients with stroke/TIA was 9 times
higher in the first few months after the initial hospitalization
and thereafter declined to double the background rate by 2
years. While several established sociodemographic, clinical,
and cardiovascular variables, including diabetes, were con-
firmed as risk factors for depression in both populations,
these associations were strongest in the reference popula-
tion, whereas physical disability and history of depression
were the key determinants of depression in those with
stroke. Depression was associated with death from all, natu-
ral, and unnatural causes in both groups, despite the poorer
survival for patients with stroke/TIA.
A strength of the population-based approach taken by Jør-
gensen et al1 was to address much of the problem of selection
bias that has limited other clinical cohort studies in different
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settings, which have produced wide-ranging frequencies of
stroke-associated depression. The necessary restrictive defi-
nition for clinical depression used likely contributed to the
slightly lower absolute frequency of depression than the widely
accepted 1 in 3 rule provided by a key meta-analysis of stud-
ies with a range of direct assessments of patients.2 However,
because any misclassification bias related to the diagnosis of
depression would have been balanced between groups, the key
findings of the high relative rate and adverse prognosis of de-
pression after acute stroke, provided in having another meth-
odological strength (a reference population), are robust and
novel. Therefore, these findings reemphasize the importance
of depression as a serious complication of stroke that extends
beyond the more obvious motor and cognitive deficits pro-
duced by having an acute ischemic or hemorrhagic lesion in
the brain.
For many years, research into the etiology of stroke-
associated depression was focused on the role of lesion loca-
tion, defined on cranial tomographic imaging. However, a
systematic review of the literature indicated that this is not a
strong factor.3 The Jørgensen et al study1 indicates the need
for a reappraisal of the importance of the stroke lesion in trig-
gering depression in the context of background predisposing
factors that include old age, female sex, living alone, having
limited education, a history of depression, and diabetes.
Modern advanced neuroimaging might shed light on the role
of damage to neural circuitry, neurotransmitter changes, and
inflammation.
However, despite its high frequency and importance, de-
pression remains grossly underdiagnosed and poorly treated
in patients with stroke.4 Part of the problem relates to the chal-
lenges of recognition in the context of cognitive impairment
and physical disability. This has led to various guidelines rec-
ommending routine screening for the disorder5,6 because iden-
tifying those at high risk based on currently known predic-
tors is unsatisfactory.7 A range of brief depression scales are
available for this purpose,8 but they are unlikely to be worth-
while unless supported by a fuller diagnostic assessment and
clear treatment plan in those with a true or probable diagno-
sis of depression.9,10
Certainly a greater awareness of stroke-associated
depression among patients, families, and health profession-
als could facilitate recognition, earlier treatment, and
improved outcomes. Because of the considerable overlap
between depression and other mood disorders, especially
anxiety, with impaired concentration and memory and
fatigue owing to various central or peripheral causes, more
(Reprinted) JAMA Psychiatry Published online September 7, 2016 E1
 Opinion Editorial

detailed neurocognitive assessment in selected patients can
be useful in establishing an underlying diagnosis and appro-
priate treatment plan. Moreover, the reassurance offered by
the early confirmation of high-level dysfunction of memory
and selected aspects of cognition can be invaluable in formu-
lating realistic rehabilitation goals and timelines for patients,
eg, in returning to work. Decisions about appropriate use of
antidepressant medication can be enhanced by having close
communication and referral pathways between stroke ser-
vices and primary care physicians, with psychiatrists and
psychologists, both within and outside of hospital.
There are important gaps in our knowledge about the most
effective treatment of stroke-associated depression. For ex-
ample, there is no robust evidence about the optimal treat-
ment of patients with mild to moderate depression, and very
limited data exist about how to treat patients with suspected
depression in whom mood cannot be formally assessed be-
cause of aphasia.11 Given the scale of a problem that is poten-
tially modifiable and can improve recovery and quality of life,
there is an urgent need for more large-scale studies to pro-
vide the necessary evidence for the prevention and manage-
ment of stroke-associated depression.

ARTICLE INFORMATION
Author Affiliation: The George Institute for Global
Health, Camperdown, Australia.
Corresponding Author: Craig S. Anderson, MD,
PhD, The George Institute for Global Health,
University of Sydney, PO Box M201, Missenden
Road, NSW 2050, Australia (canderson
@georgeinstitute.org.au).
Published Online: September 7, 2016.
doi:10.1001/jamapsychiatry.2016.1868.
Conflict of Interest Disclosures: None reported.
REFERENCES
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