Onset of Depression in Elderly Persons After Hip Fracture:
Implications for Prevention and Early Intervention of Late-Life
Eric J. Lenze, MD,?wMichael C. Munin, MD,wElizabeth R. Skidmore, PhD,zMary Amanda Dew,
F. Reynolds III, MD?
(See editorial comments by Drs. Barbara Kamholz and Ju ¨rgen Unu ¨tzer on pps 125–126.)
OBJECTIVES: To identify predictors of onset of major de-
pressive disorder (MDD) and of depressive symptoms in
subjects who suffered a hip fracture.
DESIGN: Prospective naturalistic study.
SETTING: University of Pittsburgh Medical CenterF
Shadyside, a large urban hospital in Pittsburgh, Pennsyl-
PARTICIPANTS: One hundred twenty-six elderly patients
who received surgical fixation for hip fracture and who
were not experiencing a major depressive episode at the
time of the fracture; severely cognitively impaired persons
MEASUREMENTS: Subjects were evaluated at the time of
hospital discharge using a battery of clinical measures (in-
cluding apathy measured using the Apathy Evaluation Scale
(AES), delirium, cognitive measures, social support, and
disability level). Depression was assessed at the end of the
surgical stay, 2 weeks later, and then monthly for 6 months,
evaluate symptomatology and the Primary Care Evaluation
of Mental Disorders to evaluate diagnosis of MDD.
RESULTS: Eighteen of 126 subjects (14.3%) developed
MDD after hip fracture. Of these, 11 developed MDD by
the end of the hospitalization, and seven developed MDD
between 2 and 10 weeks later. Logistic regression showed
that baseline apathy score, as measured using the AES, was
the only clinical measure associated with the development
of MDD (odds ratio51.09, 95% confidence inter-
val51.03–1.16, P5.003); 46.2% of those with high AES
scores developed MDD, versus 10.9% of those with lower
scores. In contrast, cognitive variables, delirium, disability
after hip fracture, and other factors related to the fracture
(e.g., fracture type) were not associated with MDD. A re-
peated-measures analysis with Ham-D over time as a de-
pendent variable generally confirmed these findings;
depressive symptoms were highest immediately after the
fracture, and apathy and delirium scores were associated
with higher depressive symptom levels.
CONCLUSION: The onset of MDD is common after hip
fracture, and the greatest period of risk is immediately after
the fracture. Individuals with clinical evidence of apathyare
at high risk for developing MDD, and evaluation and close
follow-up of such individuals is warranted. However, fur-
(e.g., clinical measures or biomarkers) to model adequately
the risk for MDD after hip fracture and other disabling
medical events. J Am Geriatr Soc 55:81–86, 2007.
Key words: geriatric depression; apathy; hip fracture
ive disorder (MDD).1–3For example, hip fracture has the
characteristics of a highly depressogenic stressor4because
of the sequelae of pain, immobilization, hospitalization,
surgery, and uncertain prospects of recovery.5–7Disabling
medical events are common, occurring in more than 6 mil-
lion elderly persons per year in the United States;8one study
foundthat more thanhalf of community-livingolder people
had at least one disabling medical event during a median 4-
year follow-up.9Furthermore, depression in the context of
a disabling medical event can interfere with functional re-
covery.10–16Thus, after the onset of a disabling medical
event, theremaya period ofhighrisk forlate-life depression
during which early detection or prevention strategies would
be of considerable public health benefit. To inform such
depression,17–19yet although many studies have examined
the cross-sectional rates of depressive symptoms or MDD
or elderly persons, a disabling medical event is a signif-
icant risk factor for the development of major depress-
Addresscorrespondence toDr.EricJ.Lenze, WesternPsychiatricInstituteand
Clinic, Room BT748, 3811 O’Hara Street, Pittsburgh, PA 15213.
From the?Advanced Center for Interventions and Services Research and John
A. Hartford Center of Excellence in Geriatric Psychiatry, Department of
Psychiatry,wDepartment of Physical Medicine and Rehabilitation, School of
Medicine, andzDepartment of Occupational Therapy, University of Pitts-
burgh, Pittsburgh, Pennsylvania.
r 2006, Copyright the Authors
Journal compilation r 2007, The American Geriatrics Society
after a disabling medical event, there has been surprisingly
little research examining the development of incident MDD
in this context.
It is posited that hip fracture is a good model for exam-
ining the development of late-life depression, because hip
fractures are common20and are associated with high rates
of depressive symptoms14,21,22or MDD.23Furthermore,
hip fracture has an easily identifiable onset, clear-cut pa-
thology, and predictable recovery pattern,24although even
in this ideal context, detecting depression soon after a hip
fracture can be difficult, because symptoms may be signs of
delirium or an adjustment reaction or may be unreliably
reported by severely cognitively impaired patients. Further-
more, the rapid changes in setting (e.g., from hospital to
rehabilitation facility to home) make it difficult to track a
patient longitudinally. Apathy (appearing as a lack of inter-
est or motivation) after a disabling medical event might
warn of an impending major depressive episode;25con-
versely, it has been argued that apathy in this age group
likely reflects neurodegenerative disease or even normal
signs of aging rather than depression.26In addition, com-
mon clinical factors after hip fracture such as high levels of
disability after a medical event, low levels of social support,
cognitive impairment, and delirium may be potential
predictors of depression.18,27–30
Accordingly, this study assessed a prospective cohort of
elderly hip fracture patients for the development of MDD
over 6 months. The aim was to determine when patients
were at highest risk for depression and which clinical and
demographic variables were associated with onsetof MDD;
such risk intervalandvariables potentiallycould comprise a
predictive model for late-life depression that would allow
for targeted early intervention or prevention efforts in the
context of disabling medical events. It was hypothesized
that individuals with apathy immediately after the hip frac-
ture would be at greater risk of developing MDD, because
previous research has found it to be a prominent aspect of
late-life depression.25,31,32Cognitive impairment (particu-
larly executive impairment), delirium, social support, and
level of postfracture disability were also examined as po-
tential predictors, given prior research implicating these
variables in models of risk for late-life depression.2,18,33,34
Patients consecutively admitted to an acute care hospital
with a primary diagnosis of hip fracture between March
2002 and October 2004 were approached. All subjects re-
ceived surgical repair. Inclusionary criteria were aged 60
and older, ability to sign informed consent, and freedom
from metastatic cancer. The university’s institutional review
board approved the study.
Subjects were assessed at the end of their hospital stay
using the mood module of the Primary Care Evaluation of
Mental Disorders to diagnose MDD35and the 17-item
Hamilton Depression Rating Scale (Ham-D) to examine
depressive symptoms.36These measures were repeated 2
weeks after hospital discharge and then every 4 weeks
thereafter until 26 weeks after hospital discharge. For sub-
jects found to be in a major depressive episode, whether the
episode was present at the time of the hip fracture or started
after the hip fracture was systematically ascertained using
methodology from the Structured Clinical Interview for the
Diagnostic and Statistical Manual of Mental Disorders,
Fourth Revision, axis I disorders37(SCID). Interrater reli-
ability with the Ham-D was good (0.86–0.96); all Primary
Care Evaluation of Mental Disorders MDD cases and SCID
evaluations were reviewed with a geriatric psychiatrist
(EJL) to enhance reliability.
To measure potential risk markers for depression,
demographic variables and characteristics of the fracture,
surgery, and length of surgical stay were gathered. Apathy
was measured using the clinician version of the Apathy
Evaluation Scale (AES), a measure of apathy symptomatol-
ogy;38items include ‘‘S/he has initiative,’’ ‘‘S/he has motiv-
ation,’’ and ‘‘S/he is interested in things’’ and are ratedbased
on an approximately 20-minute interview with a subject as
72, with higher scores indicating higher levels of apathy.
Cronbach alpha for the measure in this study was 0.93,
indicating that the scale was measuring a single construct.
Functional status was measured prefracture (through
structured interview during the surgical stay) and postfrac-
ture (at the end of the surgical stay) using the 13 motor
items of the Functional Independence Measure (FIM), a
measure of patients’ dependence on others for motor and
activity of daily living tasks.39Cognition was measured at
the end of the surgical stay using the Mini-Mental State
Examination40and at 2 weeks after the surgical stay using
the Mattis Initiation-Perseveration subscale (Mattis I/P) to
measure executive function41(this measure was added after
the study had started, resulting in decreased n), and the
Logical Memory Task of the Wechsler Adult Intelligence
Scale was used to measure memory.42Delirium was meas-
ured at the end of the surgical stay using the Delirium Rat-
ing Scale43(DRS), which assesses behavioral symptoms of
delirium (e.g., change in sensorium); because item 9 of the
DRS rated apathy, this item was removed from the scale for
study analyses. Social support was measured using the So-
cial Network Index, which measures number and frequency
of contacts with family and friends.44Medical comorbidity
was measured using the Cumulative Illness Rating Scale for
Geriatrics (CIRS-G), which measures overall severity of
medical problems.45Use of psychotropic medications
throughout the trial was recorded.
To examine predictors and correlates of MDD, subjects
who developed MDD were compared with those who did
not on all demographic and clinical variables, and logistic
regressions examining association of these variables with
simultaneous or subsequent development of MDD were
performed. Similarly, to examine predictors and correlates
of depressive symptoms, a repeated-measures mixed-effects
model with Ham-D score over time as dependent variable
was carried out, examining demographic and clinical vari-
ables first in a univariate model and then in a multivariate
One hundred forty-one subjects aged 60 and older who
were hospitalized for hip fracture and were able to give
informed consent (i.e., no severe delirium or dementia)
LENZE ET AL.
JANUARY 2007–VOL. 55, NO. 1JAGS
were approached. Of these, 12 refused the baseline evalu-
ation, two had severe cognitive impairment precluding fur-
ther participation, and one had MDD before the onset of
the hip fracture. Thus, 126 subjects constituted the study
group. These subjects were predominantly Caucasian
and female and remained in the acute care hospital for an
average 5.8 days.
As Figure 1 shows, 18 of 126 (14.3%) subjects devel-
oped MDD after hip fracture. Most (11/18; 61%) MDD
cases had onset of MDD symptoms before discharge from
symptoms between 2 and 10 weeks after the hospitaliza-
tion. Nonewcasesappearedbetween14and26weeks after
Table 1 compares baseline demographic and clinical
variables of those who developed MDD and those who did
not. These variables were evaluated as possible correlates of
depression using logistic regressions (dependent variable:
MDD). As Table 1 shows, only apathy was significantly
associated with time to MDD, although there was a trend
(P5.09) for delirium scores (minus item 9). In contrast,
features of the hip fracture (such as type of fracture, dis-
ability level upon hospital discharge, type of surgery) were
not associated with MDD. In addition, neither cognitive
variables (MMSE, Mattis I/P, Logical Memory Test) nor
social support were associated with MDD. In a multivariate
model including apathy and delirium scores, apathy was a
significant correlate of MDD (OR51.09, 95% CI51.02–
1.15, P5.007), whereas delirium was not (OR51.05,
95% CI50.96–1.15, P5.29). Because the construct of
apathy is similar to some features of depression (i.e., apathy
includes loss of interest, initiative, and motivation, whereas
depression includes anhedonia, anergia, and poor concen-
tration), the shared variance between AES and Ham-D
scores was examined. The shared variance was 16.5%, in-
dicating that the AES is mainly measuring features that are
unique to apathy and that the scale is not just capturing
symptoms of depression.
The course of depressive symptoms in this sample,
shown in Figure 1, also suggests that the greatest risk period
for depression is immediately after the fracture, with many
subjects having a dramatic decline in depressive symptoms
by 2 weeks after the end of their surgical hospitalization.
The same demographic and baseline clinical variables were
evaluated as possible correlates of depressive symptoms
over time using repeated-measures models (dependent vari-
able: Ham-D). In univariate repeated-measures models,
several variables were significant: age, medical illness
(CIRS-G), pre- and postfracture disability (FIM score), ap-
athy (AES), delirium (DRS), social support, MMSE, mem-
ory (LMT), and executive function (Mattis I/P) (data not
shown). In a subsequent model including age, CIRS-G,
postfracture FIM, apathy, delirium, social support, and
MMSE, apathy scores were associated with depressive
symptoms over time (F58.5, degrees of freedom (df)51,
114,P5.004),as weredeliriumscores (F55.3, df51,114,
Po.05), with a trend for CIRS-G scores (F52.8,
df51,114, P5.10); no other variables were significant.
Antidepressant use was common in this study cohort;
22.2% (28/126) of subjects were taking antidepressants
at baseline, and an additional 2.4% (3/126) initiated
antidepressant treatment during the course of the study.
Antidepressants included therapeutic doses of selective se-
rotonin reuptake inhibitors (sertraline (n57, 25–150mg/
d), citalopram (n59, 10–40mg/d), paroxetine (n56, 10–
60mg/d), escitalopram (n53, 10mg/d), fluoxetine (n51,
20mg/d)), mirtazapine (n53, 7.5–45mg/d), or venlafaxine
XR (n52, 75–300mg/d). Baseline antidepressant use was
significantly associated with likelihood of developing
MDD; 10 of 28 (35.7%) subjects taking baseline anti-
depressants developed MDD, versus eight of 98 (8.2%)
subjects not taking a baseline antidepressant (Po.001).
Baselineantidepressant usewas also significantlyassociated
with mean baseline Ham-D score ? standard deviation,
which was 12.93 ? 6.82 in the 28 taking antidepressants
versus 8.85 ? 4.37 in the 98 who were not (t53.00,
df533.6, P5.005). Because antidepressant use was likely
a proxy for prior history of depression and information was
not gathered on past history of MDD, antidepressant use
was not included in the models.
As a further examination of apathy as a correlate of
MDD, a receiver operating characteristic (ROC) analysis
was performed with AES score to explore how robustly it
could predict current and subsequent MDD. The ROC
analysis showed that the most optimal cutoff score on the
AES was 45, providing 33% sensitivity and 93.3% speci-
ficity for MDD. Thus, in this cohort of hip fracture patients
with an AES score of 45 or greater, six of 13 (46.2%) de-
veloped MDD, whereas in those with a score of 44 or less,
45 is optimal according to the ROC analysis, it excludes
67% (12/18) of the subjects who experienced MDD. For
comparison, AES scores greater than 38 are usually con-
sidered evidence of clinically relevant apathy,46suggesting
that this optimal cutoff of 45 was defining fairly high levels
of clinical apathy.
This is the first published in-depth evaluation of the onset of
MDD and depressive symptoms over time after a hip frac-
ture, as well as the first study to examine potential risk
Number of weeks post surgical hospitalization
026 10 14 182226
Number of MDD cases developing
126112 102 103 98 98 99 101
Figure 1. New cases of major depressive disorder (MDD) and
course of depressive symptoms after hip fracture; 18 of 126
(14.2%) subjects developed MDD after the fracture. Ham-
D5Hamilton Rating Scale for Depression.
DEPRESSION AFTER HIP FRACTURE
83JAGSJANUARY 2007–VOL. 55, NO. 1
factors for incident depression after hip fracture. Because
disabling medical events such as hip fracture are extremely
common in elderly persons and are robust risk factors for
depression, these findings could inform the development of
early detection and prevention strategies, in addition to in-
forming clinicians about when and how to examine
patients’ risk for MDD.
The study found that 14.3%, or one of every seven
patients, developed MDD after hip fracture. This number is
lower than the cross-sectional prevalence of MDD in other
studies of hip fracture23or other disabling medical events
but may reflect increasing prescription of antidepressants in
older people or the exclusion of severely cognitively im-
paired patients. The rate of new MDD cases in this hip
fracture sample was much higher than the community in-
cidence of MDD,47suggesting that hip fracture is a risk
factor for depression, as would be expected for a disabling
medical event.48An alternative conclusion would be that
hip fracture, which would be consistent with findings that
depressive symptoms are a risk factor for falls, hip frac-
tures,49and bone density loss.50However, few MDD cases
before hip fracture were found, suggesting that the more
likely scenario is that hip fracture is a risk factor for late-life
depression. Within this sample, characteristics of the hip
fracture (such as fracture type or posthospitalization dis-
ability level) did not contribute to the risk for depression.
Thus, it appears that hip fracture is a fairly homogeneous
phenomenon with respect to depression risk, in contrast to
other medical events such as stroke, in which specific event
characteristics such as lesion location may be predictive of
The risk of developing depression is greatest immedi-
ately after the fracture, suggesting that the first 10 weeks
and in particular the first 2 weeks, after fracture is a ‘‘risk
window’’ during which efforts to detect and prevent
depression should be the greatest. It should be noted that
the risk window for MDD after hip fracture may not be the
months poststroke,30suggesting that hip fracture and
stroke exert risk for depression in different ways.
Symptoms and signs of apathy were associated with
MDD; 46.2% of individuals with high AES scores devel-
oped MDD, compared with 10.9% with lower scores.
Thus, the hypothesis that apathy would be associated with
overlap between the phenomena of apathy and depression;
prior research has demonstratedthat apathyand depression
are different constructs,38and in this study, shared variance
between AES and Ham-D scores was low. Thus, symptoms
and signs of apathy soon after a hip fracture should be
considered evidence that a patient is at elevated risk for, or
in the early stages of, MDD. It is notable that the finding
was in a nonneurological population, because apathy in
elderly persons typically is conceptualized as resulting from
specific brainlesionsor neurodegenerativedisease31,51or as
a normal response to aging.26The findings of the current
study suggest another context in which apathy is of clinical
Table 1. Characteristics of Hip Fracture Patients and Their Relationship with the Development of Major Depressive
Disorder (MDD) After Hip Fracture
(95% Confidence Interval)
for MDD vs no MDD?
Age, mean ? SD
Male, n (%)
Caucasian, n (%)
Cumulative Illness Rating Scale score, mean ? SD
81.8 ? 8.7
10.1 ? 3.3
78.3 ? 10.8
9.8 ? 3.9
85.0 ? 8.2
47.8 ? 6.5
6.3 ? 3.8
40.3 ? 9.8
Prefracture FIM motor subscale score, mean ? SD
Postfracture FIM motor subscale score, mean ? SD
Subcapital fracture, n (%)
Prosthetic joint surgery, n (%)
Surgical length of stay, days, mean ? SD
84.2 ? 11.8
47.2 ? 11.2
5.7 ? 3.4
Apathy Evaluation Scale score, mean ? SD32.5 ? 9.0
5.9 ? 5.4
24.9 ? 3.8
23.2 ? 4.4
33.7 ? 4.4
Delirium Rating Scale score, mean ? SD
Mini-Mental State Examination score, mean ? SD
Logical Memory Test score, mean ? SD
8.3 ? 7.0
25.0 ? 3.6
23.6 ? 3.3
31.4 ? 7.9
Mattis Initiation-Perseveration scale 0.93 (0.83–1.04) .18
Social support 0.97 (0.91–1.03).25
?Results of univariate logistic regressions of each variable (except for race, because of insufficient variability) as a correlate of incident MDD after hip fracture. Of
these variables, only Apathy Evaluation Scale score was correlated with the development of MDD, with a trend for Delirium Rating Scale score.
SD5standard deviation; FIM5Functional Independence Measure.
LENZE ET AL.
JANUARY 2007–VOL. 55, NO. 1JAGS
significance; signs of disinterest and amotivation emerging
in the early recovery period from a disabling medical event
are not a normal reaction in elderly persons but often mark
the beginnings of a major depressive episode. Because clin-
ical staff are more likely to detect such signs of apathy
(typically as poor participation in rehabilitation) than usual
core features of depression,52–54this finding shows clinical
apathy to be a potentially useful tool in the clinical detec-
tion of current or impending MDD.
Depressive symptoms over time were correlated not
only with baseline apathy symptoms, but also with symp-
toms of delirium. However, interpretation of the associa-
tion between delirium and depressive symptoms is difficult.
For example, the relationship between delirium and de-
pressive symptoms may suggest that delirium is a risk factor
for development of depression but also may demonstrate
that depressive symptoms are a feature of delirium, as oth-
ers have noted.28Future research should examine whether
delirium puts elderly patients at risk for developing a
Some limitations should be noted. Most cases of MDD
developed almost immediately after the hip fracture, so it
was not possible to determine whether apathy symptoms
preceded MDD or were early prodromal signs of MDD.
The variables were, as a whole, insufficient to form a
risk index for MDD; the ROC analysis suggested that the
AES by itself would not adequately stratify older people at
risk for MDD for prevention efforts. Further research is
needed to determine how to better delineate those at
highest risk for MDD after this and other disabling medical
events. The study did not obtain a psychiatric history on
subjects and thus could not examine the interaction be-
tween current clinical features and past history of depres-
sion; baseline antidepressant use was associated with
developing MDD, likely demonstrating that antidepressant
use was a proxy for prior episodes of depression, but
this finding could not be interpreted further because of the
lack of historical data on depressive episodes. Because
of the sample size, there is limited power, which may
have produced false-negative results for some potentially
significant correlates. For example, there was a trend for
delirium to be correlated with MDD; perhaps a larger
study would find that delirium or other variables (e.g.,
executive function, social support) are significant correlates
or predictors. Finally, because of the large proportion
of subjects taking antidepressants, and also because of
subject attrition, the course of symptoms shown in Figure 1
cannot be considered a ‘‘natural’’ course of depressive
In conclusion, MDD was common after hip fracture,
particularly immediately after the fracture. Individuals with
apathy were most likely to develop MDD or depressive
symptoms. These findings have important implications for
strategies to detect depression in acutely medically ill
elderly; patients showing signs of apathy should be closely
watched for MDD. However, this finding should be
considered only a starting point for efforts to identify risk
for depression after disabling medical events. With ap-
proximately 6 million disabling medical events occurring
each year in the elderly population in the United States
alone, a rate of 14% found in the current study suggests
that more than 800,000 episodes of MDD per year occur in
older people as a consequence of disabling medical
events. The enormity of this problem dictates that further
research is needed into potential risk factors (psychosocial
and biological55) for depression after disabling medical
events such as hip fracture to aid the development of
effective preventive and treatment strategies for late-life
The investigators would like to acknowledge the staff of the
University of Pittsburgh Medical Center (UPMC) Shadyside
Hospital and UPMC Presbyterian Hospital for their efforts
with this study.
Financial Disclosure: This research was supported by
National Institute of Mental Health (NIMH) Grants K23
MH64196, P30 MH52247, and P30 MH71944 and the
UPMC Endowment in Geriatric Psychiatry. Dr. Lenze has
received grant support from Forest, Pfizer, and Johnson &
Johnson. Dr. Munin received grant and research support
from Allergan, Inc. Dr. Whyte received grant and research
support from Pfizer. Dr. Reynolds received grant and
research support from Glaxo Smith Kline, Forest, Pfizer,
Author Contributions: Dr. Lenze was the principal in-
vestigator of this study, oversaw all aspects of it, and wrote
the manuscript. Dr. Munin and Dr. Reynolds supervised Dr.
Lenze and had a role in study design, data acquisition and
interpretation, and preparation of the manuscript. Dr. Dew,
Dr. Skidmore, and Dr. Rogers had a role in study design,
data acquisition and interpretation, and preparation of the
manuscript. Dr. Whyte and Ms. Begley had a role in data
interpretation and preparation of the manuscript. Ms.
Quear carried out all aspects of the study and had a role
in preparation of the manuscript.
Sponsor’s Role: The sponsor, NIMH, had no role in
the design, methods, subject recruitment, data collection,
analysis, or preparation of the manuscript.
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