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For numbered affiliations see
end of article.
Correspondence to
Dr Elene Janberidze, European
Palliative Care Research Centre,
Department of Cancer Research
and Molecular Medicine, Faculty
of Medicine, Norwegian
University of Science and
Technology (NTNU),
Kunnskapssenteret 4. etg.,
St. Olavs Hospital,
Trondheim N-7006 Norway;
elene.janberidze@ntnu.no
Received 16 May 2014
Revised 13 October 2014
Accepted 19 December 2014
To cite: Janberidze E,
Pereira SM, Hjermstad MJ,
et al. BMJ Supportive &
Palliative Care Published Online
First: [please include Day
Month Year] doi:10.1136/
bmjspcare-2014-000722
Depressive symptoms in the last
days of life of patients with cancer:
a nationwide retrospective
mortality study
Elene Janberidze,1,2 Sandra Martins Pereira,3 Marianne Jensen Hjermstad,1,4
Anne Kari Knudsen,1,2 Stein Kaasa,1,2 Agnes van der Heide,5
Bregje Onwuteaka-Philipsen,3 on behalf of EURO IMPACT
ABSTRACT
Objectives Depressive symptoms are common
in patients with cancer and tend to increase as
death approaches. The study aims were to
examine the prevalence of depressive symptoms
in patients with cancer in their final 24 h, and
their association with other symptoms,
sociodemographic and care characteristics.
Methods A stratified sample of deaths was
drawn by Statistics Netherlands. Questionnaires
on patient and care characteristics were sent to
the physicians (N=6860) who signed the death
certificates (response rate 77.8%). Adult patients
with cancer with non-sudden death were
included (n=1363). Symptoms during the final
24 h of life were assessed on a 1–5 scale and
categorised as 1=no, 2–3=mild/moderate and
4–5=severe/very severe.
Results Depressive symptoms were registered in
37.6% of the patients. Patients aged 80 years or
more had a reduced risk of having mild/
moderate depressive symptoms compared with
those aged 17–65 years (OR 0.70; 95% CI 0.50
to 0.99). Elderly care physicians were more likely
to assess patients with severe/very severe
depressive symptoms than patients with no
depressive symptoms (OR 4.18; 95% CI 1.48 to
11.76). Involvement of pain specialists/palliative
care consultants and psychiatrists/psychologists
was associated with more ratings of severe/very
severe depressive symptoms. Fatigue and
confusion were significantly associated with
mild/moderate depressive symptoms and anxiety
with severe/very severe symptoms.
Conclusions More than one-third of the
patients were categorised with depressive
symptoms during the last 24 h of life.
We recommend greater awareness of
depression earlier in the disease trajectory to
improve care.
Janberidze E, et al. BMJ Supportive & Palliative Care 2015;0:1–9. doi:10.1136/bmjspcare-2014-000722
Research
INTRODUCTION
Prevalence rates of depression and anxiety
in patients with long-term physical disor-
ders are about 25–30%.1 Also, in patients
with advanced cancer, depressive symp-
toms are commonly experienced.2 The
reported prevalence rates in this patient
population vary considerably from 2% to
56% depending on the assessment method
used.3 Self-reporting of subjective symp-
toms in patients with cancer is generally
considered as the ‘gold standard’ of assess-
ment.4 However, in the last days of life,
compliance with self-report measures vary
dramatically5 since many patients may
have multiple concurrent symptoms and a
high symptom burden,6 for example, con-
fusion, communication difficulties, and/or
physical and cognitive disability.7 Thus, in
this phase, ratings of patients’ symptoms
by healthcare providers and/or their next
of kin may be a feasible solution. Proxy
ratings of this kind are reported to be rea-
sonably adequate.8 The benefits of the
proxy ratings may outweigh the limitations
when studying groups that would other-
wise be excluded from studies.8–10
Different sociodemographic character-
istics and symptoms have been identified as
being associated with depression in popu-
lations with cancer. Those characteristics
include younger age,11 female gender,12
marital status13 and certain cancer diagno-
ses such as breast14 and pancreatic
cancer.15 Most patients with cancer have
several symptoms during their disease tra-
jectory with fatigue, pain and dyspnoea
being among the most common,6 leading
to an impaired quality of life.16 Many of
these somatic symptoms may overlap with
1
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Research
the nine symptoms included in the diagnostic criteria of
depression in the Diagnostic and Statistical Manual of
Mental Disorders (DSM) V,17 for example, fatigue.18
The present study makes use of survey data from a
large nationwide retrospective death certificate study
from the Netherlands conducted in 2005,19 which
examines different aspects of end-of-life practice. Data
on depression and other symptoms prior to death
were registered by the attending physicians retrospect-
ively, and were used to address the following research
questions:
1. What was the prevalence of depressive symptoms in
patients with cancer in the final 24 h of life based on
reports from the attending physician?
2. Were there any associations between depressive symp-
toms as reported by physicians and the patients’
sociodemographic characteristics and characteristics
of care?
3. Were there any associations between depressive symp-
toms and the following common symptoms: pain, vomit-
ing, fatigue, dyspnoea, confusion and anxiety?
METHODS
Study design
A nationwide retrospective death certificate study was
performed in 2005 analogous to three previously con-
ducted studies.20–22 A stratified sample of deaths was
drawn by Statistics Netherlands (http://www.cbs.nl)
which receives death certificates of all deaths in the
country. Depending on the cause of death registered on
the death certificate, the death was assigned to one of
five strata (1–5). Patients with instant death (eg, car acci-
dent) were assigned to stratum 1. Cases from stratum 1
did not receive any assistance from a physician prior to
death. Consequently, questionnaires were not sent, but
the cases were retained in the sample. All other deaths
were assigned to strata 2–5, with each stratum having a
higher likelihood of having a medical end-of-life deci-
sion preceding death.19 The final sample contained half
of the cases in stratum 5, 25% of the cases in stratum 4,
12.5% of those in stratum 3, 8.3% of those in stratum
2, and all cases in stratum 1 corresponding with the pre-
vious publication.19 Patients with cancer registered as
the cause of death were included in stratum 4.
For all sampled deaths, a questionnaire was mailed
to the physicians who had signed the death certificate,
with a letter including the name and date of birth of
the diseased person. This information allowed physi-
cians to identify the patient and to retrieve relevant
information from the patient’s medical record.
According to Dutch legislation, there was no need for
ethical committee approval.19
Population
Of 6860 questionnaires mailed, 5342 were returned,
giving a response rate of 77.8%. For the present ana-
lysis, cases were excluded if (1) the physicians had
their very first contact with the patient after the
2 Janberidze E, et al. BMJ Supportive & Palliative Care 2015;0:1–9. doi:10.1136/bmjspcare-2014-000722
patient’s death (n=848), (2) the patient died suddenly
or unexpectedly according to the physician (n=635),
(3) the patient was younger than 17 years old
(n=121), (4) the cause of death was other than cancer
(n=1508) and if (5) the patient was unconscious in
the last days of life (n=709). This resulted in a sample
of 1521 patients, with missing information on depres-
sive symptoms in 10.4% (n=158). Thus, the final
study population consisted of 1363 cases.
Measures
A four-page questionnaire was completed 1–2 months
after the patient’s death. It included information on
care received by the patient, such as the medical spe-
cialty of the attending physician, and whether other
healthcare providers were involved in the care of the
patient in the last month of life (eg, pain specialist).
The prevalence and intensity of the following symp-
toms were rated by the physician who signed the
death certificate: depression, pain, vomiting, fatigue,
dyspnoea, confusion and anxiety in the final 24 h
before death. Symptom intensity was registered on a
rating scale ranging from 1=no symptoms to 5=very
severe symptoms.
Sociodemographic characteristics (eg, gender, age at
death, marital status, place of death) and underlying
cause of death were captured from the death certificates,
which were linked to the questionnaires received.
Statistical analysis
In this study, the scale used for rating symptom inten-
sity was categorised as 1=no, 2=mild, 3=moderate,
4=severe and 5=very severe, and further recoded
into three groups: 1=no, 2–3=mild/moderate and
4–5=severe/very severe. Sociodemographic character-
istics, care characteristics and patients’ physician-
reported symptoms were chosen as independent
variables based on the existing literature.6 11–13
Intensity of depressive symptoms was defined as the
dependent variable divided into three categories: no
(reference), mild/moderate and severe/very severe.
The following analyses were performed:
1. The association between independent and dependent
variables was analysed using the χ2 test ( p<0.05).
Weighted percentages were applied to adjust for differ-
ences in the percentages of deaths sampled from each of
the five strata, and differences in response rates in rela-
tion to the age, sex, marital status, region of residence
and cause of death of the patients. After adjustment, the
percentages were extrapolated to cover a 12-month
period to reflect all deaths in the Netherlands in 2005.
As a result of this weighting procedure, the percentages
presented cannot be derived from the absolute numbers
presented.
2. Multinomial logistic regression analyses were used to
further study the association between independent and
dependent variables. No weighting procedure was
applied. In the first step of this analysis, all independent
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variables that showed a significant association with the
dependent variable were entered into the model, except
for place of death. This variable was left out from the
analysis because of its high correlation with the medical
specialty of the attending physician. Using a backwards
stepwise approach, variables were excluded until the last
step of the analysis in which only variables with a statis-
tical significance ( p<0.05) remained in the model.
Results are presented in terms of p values and ORs
along with 95% CIs. All of the statistical analyses
were performed with IBM SPSS Statistics V.19.0 for
Windows (IBM Corporation, Armonk, New York,
USA).
RESULTS
Patient characteristics and prevalence of depressive
symptoms
Seventy-two per cent of the patients were 65 years or
above, 43% were female and more than 50% of the
Research
patients were married. Forty-eight per cent died at
home, 24% in hospital, 15% in nursing homes and
6% in residential homes. General practitioners
attended to 60% of the patients before or at the time
of death (table 1). The overall prevalence of depres-
sive symptoms in the last 24 h of life was 37.6%,
including 31.8% with mild/moderate symptoms and
5.8% with severe/very severe depressive symptoms
(figure 1).
Sociodemographic and care characteristics
Table 1 shows the association between the presence of
depressive symptoms (no, mild/moderate, severe/very
severe) and patients’ sociodemographic and care
characteristics. There were more women in the group
with severe/very severe depressive symptoms (53%)
than in the other two groups (44% with no symptoms
and 40% with mild/moderate symptoms). A larger
proportion of patients with no depressive symptoms

Table 1 Association between depressive symptoms and sociodemographic and care characteristics in patients with cancer (n=1363)
Presence and absence of depressive symptoms in patients with cancer at the end of life
Mild/moderate Severe/very Total
No (n=855) (n=434) severe (n=74) (n=1363)
Variable N (%)* N (%)* N (%)* N (%)* p Value
Sociodemographic characteristics
Gender
Male 477 (56) 263 (60) 35 (47) 775 (57) <0.001
Female 378 (44) 171 (40) 39 (53) 588 (43)
Age, years
17–64 260 (27) 147 (31) 22 (27) 429 (28) <0.001
65–79 348 (43) 201 (47) 35 (48) 584 (44)
80 and older 247 (30) 86 (22) 17 (25) 350 (28)
Marital status
Married 483 (57) 263 (61) 44 (61) 790 (59) <0.001
Not married 372 (43) 171 (39) 30 (39) 573 (41)
Care characteristics
Place of death
Hospital 159 (22) 98 (26) 19 (30) 276 (24) <0.001
Nursing home 136 (17) 55 (13) 5 (7) 196 (15)
Residential home 56 (7) 18 (4) 7 (10) 81 (6)
Home 438 (47) 236 (51) 39 (48) 713 (48)
Other setting 66 (7) 27 (6) 4 (5) 97 (7)
Medical specialty of attending physician†‡
General practitioner 542 (60) 276 (60) 50 (63) 868 (60) <0.001
Clinical specialist 154 (22) 97 (26) 19 (30) 270 (24)
Elderly care physician 146 (18) 60 (14) 5 (7) 211 (16)
Which caregivers were involved in the care of the patient during the last month before death (beside yourself)?
Pain specialist/palliative care consultant 105 (11) 66 (14) 20 (27) 191 (13) <0.001
Psychiatrist/psychologist 16 (2) 12 (3) 8 (11) 36 (3) <0.001
Spiritual caregiver 128 (15) 62 (15) 15 (22) 205 (15) <0.001
Volunteer 131 (15) 76 (17) 11 (15) 218 (15) <0.001
Data present the absolute number of patients; however, the percentages are weighted.
*Percentages presented are weighted to adjust for the sampling fraction, non-response and random sampling deviation, to make them representative of all
deaths in 2005.
†The attending physicians were general practitioners, clinical specialists or elderly care physicians.
‡The sample included 14 physicians with an unknown specialty.

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Research
Figure 1 Bar chart presenting physician-reported depressive
symptoms in patients with cancer during the last 24 h of life.
Percentages presented are weighted to adjust for the sampling
fraction, non-response and random sampling deviation, to make
them representative of all deaths in 2005.
were 80 years or older compared with patients in the
other two groups (30% vs 22% with mild/moderate
symptoms and 25% with severe/very severe depressive
symptoms). There was an uneven distribution of
patients categorised with severe/very severe, mild/
moderate or no depression across places of death
( p<0.001). Among the 713 patients who died at
home, 48% had severe/very severe depressive symp-
toms; however, patients who died in nursing homes
were less often categorised as having severe/very
severe depressive symptoms than patients with mild/
moderate or no depressive symptoms (7% vs 13%
and 17%). Patients with severe/very severe depressive
symptoms were less frequently attended to by elderly
care physicians than patients with mild/moderate or
no depressive symptoms (7% vs 14% and 18%).
Patients with severe/very severe depressive symptoms
more often had additional professionals involved in
their care than patients with mild/moderate or no
depressive symptoms: pain specialists or palliative care
consultants (27% vs 14% and 11%), psychiatrists or
psychologists (11% vs 3% and 2%) and spiritual care-
givers (22% vs 15% and 15%).
Other subjective symptoms
Pain was reported as being mild/moderate in 46% of
the patients, against severe/very severe in 33%.
Anxiety was mild/moderate in 47% and severe/very
severe in 14%, while 73% reported severe/very severe
fatigue (table 2). Physician-reported subjective symp-
toms differed across the three categories of intensity
of depressive symptoms. More severe/very severe
symptoms were observed in patients with severe/very
severe depressive symptoms as compared with patients
with mild/moderate or no depressive symptoms; for
example, 63% of the patients with severe/very severe
depression symptoms, 18% of patients with mild/
4 Janberidze E, et al. BMJ Supportive & Palliative Care 2015;0:1–9. doi:10.1136/bmjspcare-2014-000722
moderate depressive symptoms, and 8% of patients
without depression had severe/very severe anxiety.
Multinomial logistic regression analyses
Patients who were 80 years and older had a reduced
risk of having mild/moderate depressive symptoms
compared with those who were 17–65 years (OR 0.70,
95% CI 0.50 to 0.99) (table 3). Elderly care physicians
were more likely to assess patients with severe/very
severe depressive symptoms than patients with no
depressive symptoms (OR 4.18; 95% CI 1.48 to
11.76). Pain specialists or palliative care consultants
(OR 2.07; 95% CI 1.10 to 3.88) and especially psy-
chologists or psychiatrists (OR 4.83; 95% CI 1.59 to
14.70) were more likely to be involved in the care of
the patients with severe/very severe depressive symp-
toms than in the care of patients with no depressive
symptoms. Three symptoms fatigue (OR 1.83; 95% CI
1.36 to 2.46), anxiety (OR 1.92; 95% CI 1.33 to 2.77)
and confusion (OR 1.49; 95% CI 1.05 to 2.11)
occurred more frequently in patients with mild/moder-
ate depressive symptoms compared with patients with
no depressive symptoms. In addition, anxiety was asso-
ciated with reporting severe/very severe depressive
symptoms (OR 15.06; 95% CI 8.45 to 26.84).
DISCUSSION
This study applied data from a large population-based
study conducted in 2005 in the Netherlands to
examine depressive symptoms in patients with cancer
at the end of life. Attending physicians reported
depressive symptoms as being present in 37.6% of
patients, although only 5.8% were categorised as
severe/very severe. Patients who were 80 years and
older had a reduced risk of having mild/moderate
depressive symptoms compared with those aged 17–
65 years. Involvement of specialists in the care of the
patient during the last month before death was asso-
ciated with severe/very severe depressive symptoms.
Fatigue and confusion occurred more frequently in
patients categorised with mild/moderate depressive
symptoms, while anxiety was the only symptom asso-
ciated with both mild/moderate and severe/very severe
depressive symptoms.
The presented results should be interpreted with
caution. First, we used physicians as proxies for report-
ing symptoms in patients with cancer, which may have
led to an underestimation of symptom severity or fre-
quency, as physicians in general are likely to underesti-
mate the presence of symptoms when compared with
patient self-report.23–26 However, even if patients’ self-
report of subjective symptoms is considered to be the
gold standard in palliative care,4 the use of proxy
ratings may allow for inclusion of patients who would
otherwise not be able to participate due to, for
example, cognitive or physical impairment. Second,
the study was retrospective and the time interval
between death and mailing the questionnaire varied
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Research

Table 2 Association between depressive symptoms and other symptoms in patients during the last 24 h before death (n=1363)
Presence and absence of depressive symptoms in patients with cancer at the end of life
Mild/moderate Severe/very Total
No (n=855) (n=434) severe (n=74) (n=1363)
Symptoms (missing) N (%)* N (%)* N (%)* N (%)* p Value
Pain (12%)
No pain 199 (25) 66 (16) 9 (14) 274 (21) <0.001
Mild/moderate pain 388 (45) 29 (40) 627 (46)
Severe/very severe pain 265 (30) 155 (35) 35 (46) 455 (33)
Vomiting (13%)
No vomiting 629 (76) 64 (64) 38 (52) 931 (71) <0.001
Mild/moderate vomiting 147 (16) 119 (27) 21 (31) 287 (20)
Severe/very severe vomiting 73 (8) 21 (9) 12 (17) 127 (9)
Fatigue (12%)
No fatigue 65 (9) 6 (2) 2 (3) 73 (6) <0.001
Mild/moderate fatigue 189 (24) 70 (17) 11 (16) 270 (21)
Severe/very severe fatigue 590 (67) 354 (81) 61 (81) 1005 (73)
Dyspnoea (12%)
No dyspnoea 325 (38) 104 (23) 16 (20) 445 (32) <0.001
Mild/moderate dyspnoea 266 (31) 188 (43) 28 (38) 482 (35)
Severe/very severe dyspnoea 259 (31) 139 (34) 30 (42) 428(33)
Confusion (12%)
No confusion 510 (58) 122 (26) 14 (17) 646 (46) <0.001
Mild/moderate confusion 248 (30) 233 (55) 36 (51) 517 (39)
Severe/very severe confusion 94 (12) 76 (19) 23 (32) 193 (15)
Anxiety (11%)
No anxiety 470 (54) 73 (16) 2 (2) 545 (39) <0.001
Mild/moderate anxiety 311 (38) 283 (66) 26 (35) 620 (47)
Severe/very severe anxiety 72 (8) 75 (18) 46 (63) 193 (14)
Data present the absolute number of patients; however, the percentages are weighted.
*Percentages presented are weighted to adjust for the sampling fraction, non-response and random sampling deviation, to make them representative of all
deaths in 2005.

between 1 and 2 months, which may have caused a
recall error. Missing data on depressive symptoms
(10.4%) probably illustrate some difficulties that physi-
cians may have had in assessing depression or recalling
information and could engender bias. However, owing
to the large sample size, there are data on depressive
symptoms in 1363 patients, which increases the reli-
ability. Furthermore, the major group of attending phy-
sicians included general practitioners (60%) who had
been the patients’ family doctors for several years.
Thus, they did not only sign the death certificates or
attend patients during the last days of life but were also
familiar with the patient and relatives. Third, no stan-
dardised measure with validated cut-off scores was
used for reporting, and the physicians were not asked
if they assessed depression with any formal tools in the
last 24 h before death. We also lack information on the
use of medication such as antidepressants, other psy-
chotropic drugs and opioids which may have led to
fatigue, confusion or development of other distressing
symptoms at the end of life. However, from other
studies, we know that antidepressants are often pre-
scribed close to death and in fact so late that the
therapeutic effects may be questionable.27 28 Detailed
registration of interventions for depressive symptoms,
duration of receiving antidepressant medication, infor-
mation of when depression was first identified and dur-
ation of depressive symptoms would have been given
important information about depression and treatment
outcomes; however, this was beyond the scope of the
death certificate study. No control group was included
as the primary aim of the study was to describe the
existing practice of end-of-life care in the Netherlands.
The major strength of this study is related to the
sample size including 1363 patients with cancer at the
end of life. The study included information on
patients extracted from the death certificates in the
Netherlands, and involved different care settings
across the country, making the results representative
of the entire cancer population in the Netherlands.
Furthermore, the response to the questionnaire was
high (77.8%).
Prevalence rates of depressive symptoms
In general, a comparison of prevalence rates is chal-
lenging partly due to the different study designs,

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Research

Table 3 Variables associated with depressive symptoms in multinomial logistic regression analyses (N=1363)
Presence and absence of depressive symptoms in patients with cancer at the end of life

Mild/moderate (n=434) Severe/very severe (n=74)

Variable OR (95% CI) p Value OR (95% CI) p Value
Age
17–64 1.00 1.00
65–79 1.09 (0.83 to 1.44) 0.530 0.55 (0.84 to 2.89) 0.162
80 and older 0.70 (0.50 to 0.99) 0.043 1.52 (0.71 to 3.22) 0.277
Medical specialty of attending physician*
General practitioner 1.00 1.00
Clinical specialist 1.30 (0.96 to 1.76) 0.095 1.16 (0.62 to 2.18) 0.641
Elderly care physician 1.13 (0.78 to 1.62) 0.517 4.18 (1.48 to 11.76) 0.007
Which caregivers were involved in the care of the patient during the last month before death (beside yourself)?
Pain specialist/palliative care consultant
No 1.00 1.00
Yes 1.16 (0.82 to 1.64) 0.412 2.07 (1.10 to 3.88) 0.023
Psychiatrist/psychologist
No 1.00 1.00
Yes 1.37 (0.59 to 3.21) 0.467 4.83 (1.59 to 14.70) 0.006
Symptoms during the last 24 h before death
Fatigue
No 1.00 1.00
Yes 1.83 (1.36 to 2.46) <0.001 1.46 (0.73 to 2.91) 0.282
Anxiety
No 1.00 1.00
Yes 1.92 (1.33 to 2.77) <0.001 15.06 (8.45 to 26.84) <0.001
Confusion
No 1.00 1.00
Yes 1.49 (1.05 to 2.11) 0.025 1.48 (0.79 to 2.79) 0.223
No weighting procedure was conducted during multinomial logistic regression analysis. Bold numbers represent ORs and 95% CIs showing statistically
significant difference (ORs differs significantly from 1.00) between the categories of mild/moderate or severe/very severe depressive symptoms compared
with the group with no depressive symptoms (reference category).
The variables not reaching statistical significance in multinomial logistic regression were: spiritual caregiver involved in the care of the patient for the last
month before death, patients’ marital status, volunteer involved in the care of the patients for the last month before death, physical symptoms such as
pain, vomiting, dyspnoea and patients’ gender.
*The attending physicians were general practitioners, clinical specialists or elderly care physicians.

inclusion of patients with different survival time, and
use of different assessment or reporting methods (eg,
self-report vs diagnostic tools or proxy ratings). A pre-
vious study from the Netherlands examined primary
care patients with cancer at a median of 15 weeks
before death.29 Depressed mood was reported by
general practitioners using a scale from 1 (not
depressed) to 5 (very depressed). According to a
cut-off score of 2, the prevalence rate for depressive
symptoms was 14%, which corresponds with our
results (17%) when using the same threshold.
Diagnosing depression is challenging, especially in
patients with other somatic illnesses where symptoms
such as fatigue can be related to the cancer, its treat-
ment or interpreted as a sign of depression according
to the DSM-V criteria.17 Unsystematic assessment of
symptoms,30 lack of communication skills31 and insuffi-
cient training of healthcare providers to recognise
depressive symptoms at the end of life could be the
most important explanations.32 The attending
physicians reporting the present data were not specific-
ally trained to identify depression at the end of life, or
to distinguish this from, for example, fatigue or late
stage infirmity. On the other hand, initiation of psycho-
logical interventions near the end of life may some-
times be thought to be too late or symptoms could be
regarded as a normal part of the dying process.33
Sociodemographic and care characteristics
Our results regarding age were inconclusive and
cannot confirm results from other studies showing that
younger age may be associated with depression.11 The
association between severe/very severe depressive
symptoms and elderly care physicians might partly be
explained by the fact that patients in need of specialist
care have a higher symptom burden than patients not
requiring specialist care.34 Furthermore, specialists are
expected to have more experience with patients having
complex conditions and may thus identify patients
with cancer with depressive symptoms more easily

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than general practitioners would.35 Additional profes-
sional caregivers besides the responsible physician
involved in the management of patients with cancer in
the last month before death (eg, pain specialist) appear
to facilitate more precise patient identification in need
of symptom treatment. Specialists in general may tend
to systematically assess and be able to diagnose the
patients with complex conditions. However, our data
showed that additional specialists were involved only
in a minor group of the patient cohort.
Symptoms
Patients with advanced cancer often experience symp-
toms that are coexisting and interdependent, espe-
cially when facing the end of life.6 36 37 Studies show
an association between uncontrolled physical symp-
toms, such as pain, and depression,38 39 but the caus-
ality of this relationship is unclear.38 In this study, the
patients were reported to have a relatively high
symptom burden in the last 24 h of life; for example,
79% of the patients had pain (46% reported as mod-
erate and 33% as severe). In the univariate analyses,
an association between pain and depressive symptoms
was observed. However, unexpectedly, no such associ-
ation was found in the multinomial logistic regression.
In this study, there was an association between
involvement of pain specialists in patient treatment
and severe depressive symptoms. This may indicate
that patients with depressive symptoms have a
complex symptomatology and may need a multidiscip-
linary palliative care approach. Data on the actual
pain treatment were not available.
Fatigue is known to be more frequent and severe
among depressed than non-depressed patients.40
Diagnosis of depression according to the DSM-V cri-
teria17 is established if five of nine criteria symptoms are
present, with fatigue or loss of energy being one of
these. Our data showed that 73% of the patients were
experiencing severe/very severe fatigue in the final 24 h
before death. Healthcare providers may have inter-
preted fatigue as part of the dying process, a sign of
depression, or something that may have contributed to
the development of depression in patients with both
symptoms. In addition, anxiety was the only variable
associated with both mild/moderate and severe/very
severe depressive symptoms. This could be explained by
the interdependent nature of those two conditions.37
The seemingly high prevalence of symptoms in this
study, and of depressive symptoms in particular,
points to a need to increase awareness of thorough
symptom assessment throughout the cancer disease
trajectory. According to the WHO’s revised definition
of palliative care,41early integration of palliative care
in the management of patients with cancer is recom-
mended.42 Introducing palliative care early to the
patients with its systematic approach to symptom
assessment increases the awareness and attention to
symptoms at an earlier stage and results in better
Janberidze E, et al. BMJ Supportive & Palliative Care 2015;0:1–9. doi:10.1136/bmjspcare-2014-000722
Research
symptom control and quality of life, also at the end of
life.42–46 For example, in the well-known study by
Temel et al,42 patients with non-small cell lung cancer
who were randomised to palliative care had signifi-
cantly fewer depressive symptoms than those in the
standard group.
CONCLUSIONS
This study showed that more than one-third of
patients with cancer were rated as having mild/moder-
ate to severe/very severe depressive symptoms by the
attending physicians during the last 24 h of life.
Multiple symptoms, and especially depressive symp-
toms, in patients with cancer at the end of life still call
for special attention. Improved knowledge among
healthcare providers about assessment, classification
and treatment of depression and depressive symptoms
in patients with advanced cancer would be important
to optimise cancer patient care throughout the disease
trajectory.
Author affiliations
1
European Palliative Care Research Centre (PRC),
Department of Cancer Research and Molecular
Medicine, Faculty of Medicine, Norwegian University
of Science and Technology (NTNU), Trondheim,
Norway
2
Department of Oncology, St. Olavs Hospital,
Trondheim University Hospital, Trondheim, Norway
3
Department of Public and Occupational Health, VU
University Medical Center, and EMGO+ Institute
for Health and Care Research, VUmc Expertise
Center for Palliative Care, Amsterdam, Netherlands
4
Regional Centre for Excellence in Palliative Care,
South Eastern Norway, Oslo University Hospital,
Oslo, Norway
5
Department of Public Health, Erasmus Medical
Center, Rotterdam, The Netherlands
Acknowledgements The authors thank the following EURO
IMPACT collaborators for their contribution.
Collaborators This article is part of the European Intersectorial
and Multidisciplinary Palliative Care Research Training (EURO
IMPACT). EURO IMPACT is funded by the European Union
Seventh Framework Programme (FP7/2007–2013, under grant
agreement n° [264697]). EURO IMPACT aims to develop a
multidisciplinary, multi-professional and inter-sectorial
educational and research training framework for palliative care
research in Europe. EURO IMPACT is coordinated by Professor
Luc Deliens, Professor Lieve Van den Block, Zeger De Groote,
Joachim Cohen and Koen Pardon of the End-of-Life Care
Research Group, Ghent University & Vrije Universiteit Brussel,
Brussels, Belgium. Other partners are: Anneke Francke, Luc
Deliens and Roeline Pasman, VU University Medical Center,
EMGO Institute for health and care research, Amsterdam, The
Netherlands; Richard Harding and Irene J Higginson, King’s
College London, Cicely Saunders Institute, London, and Cicely
Saunders International, London; and Sarah Brearley and Sheila
Payne, International Observatory on End-of-Life Care,
Lancaster University, Lancaster, UK; Augusto Caraceni, EAPC
Research Network, Trondheim, Norway; and Fondazione
IRCCS Istituto Nazionale dei Tumori, Milan, Italy, and Guido
Miccinesi, Cancer Research and Prevention Institute, Florence,
7
 Downloaded from http://spcare.bmj.com/ on February 28, 2015 - Published by group.bmj.com
Research
Italy; Sophie Pautex, EUGMS European Union Geriatric
Medicine Society, Geneva, Switzerland; Karen Linden, Springer
Science and Business Media, Houten, The Netherlands.
Contributors BO-P and AVDH were responsible for the study
concept and devised the questionnaire. Statistics Netherlands
made the stratification analysis. EJ led the statistical analysis and
writing of the paper; all co-authors commented on the draft
and agree on the final content.
Funding This study was funded by the Netherlands
Organisation for Health Research and Development (ZonMw),
grant number 1151.0001, and the VU University Medical
Center, EMGO Institute for Health and Care Research,
Department of General Practice & Elderly Care medicine, and
the Department of Public and Occupational Health,
Amsterdam, The Netherlands.
Competing interests None.
Provenance and peer review Not commissioned; externally
peer reviewed.
Data sharing statement EJ, BOP and AVDH have access to the
full data set.
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Depressive symptoms in the last days of life

of patients with cancer: a nationwide
retrospective mortality study
Elene Janberidze, Sandra Martins Pereira, Marianne Jensen Hjermstad,
Anne Kari Knudsen, Stein Kaasa, Agnes van der Heide and Bregje
Onwuteaka-Philipsen

BMJ Support Palliat Care published online February 9, 2015

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