Original Article

Longitudinal observation of anxiety and depression among

palliative care cancer patients
Corinna Sewtz1, Wiebke Muscheites1, Christina Grosse-Thie1, Ursula Kriesen1, Malte Leithaeuser1,2,
Dietrich Glaeser1,3, Philipp Hansen1, Guenther Kundt4, Georg Fuellen4, Christian Junghanss1
1
Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany; 2Internal
Medicine Private Practice, Rostock, Germany; 3Medical Clinic III, Hematology, Oncology, Hemostaseology, Palliative Care and Complementary
Medicine, Rostock Südstadt Hospital, Germany; 4Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University
Medical Center, Germany
Contributions: (I) Conception and design: C Junghanss, C Sewtz, W Muscheites; (II) Administrative support: U Kriesen, C Grosse-Thie, D Glaeser;
(III) Provision of study materials or patients: U Kriesen, C Grosse-Thie; (IV) Collection and assembly of data: C Sewtz, W Muscheites; (V) Data
analysis and interpretation: C Junghanss, C Sewtz, G Kundt; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
Correspondence to: Dr. med. Corinna Sewtz. Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University
Medical Center, Ernst-Heydemann-Strasse 6, 18057 Rostock, Germany. Email: corinna.sewtz@uni-rostock.de.

Background: Anxiety and depressive symptoms are commonly reported to have a high prevalence in
advanced cancer patients. However, whether the severity of the symptoms change during a stay in a palliative
care unit (PCU) and after discharge home has not been studied thus far. This prospective, longitudinal,
single-center study screened for anxiety and depression as measured on the German version of Hospital
Anxiety and Depression Scale (HADS-D) in a palliative care (PC) cancer cohort at three different time
points.
Methods: Consecutive patients (N=206) admitted to a PCU were evaluated of whom N=102 could be
enrolled. Patients were screened for anxiety and depression using the HADS-D questionnaire: 24 h after
admittance (P1), within 24 h before discharge (P2) and 2 weeks after discharge (P3). Longitudinal changes
and influencing factors were determined.
Results: Nearly 80% of all patients had at least at one time point a HADS score ≥8 indicating a clinically
meaningful symptom burden. The P1 mean scores were 7.1±3.3 (anxiety) and 8.9±4.6 (depression).
Depression was associated with underlying cancer type (P<0.05). Anxiety and depression stabilized during
hospitalization (P2). However, a significant deterioration after discharge (P3) was observed (anxiety P=0.046;
depression P=0.003), in particular in older patients (>65 years) and higher ECOG status (≥3). Patients with a
short time since first diagnosis (<1 year) had significantly higher symptom burden compared to patients with
a longer disease course. Participation was 50% emphasizing the difficulty to study PC patients. Most patients
had advanced cancers (99%). Underlying cancer types consisted of a broad variety of solid tumors including
15% hematological cases. Median survival was 1.1 months.
Conclusions: The high prevalence of anxiety and depressive symptoms points to the need for
psychological support. All PC patients should be screened for psychological distress to identify those in need
of further assessment and treatment. The deterioration at home suggests the need for improved outpatient
management, including home-based psychological support. Caregivers should be aware of the psychological
vulnerability of newly diagnosed cancer patients, patients with lower functional status and higher age.

Keywords: Palliative care (PC); advanced cancer patients; anxiety and depression; HADS questionnaire

Submitted Jun 30, 2020. Accepted for publication Dec 14, 2020.
doi: 10.21037/apm-20-1346
View this article at: http://dx.doi.org/10.21037/apm-20-1346

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(4):3836-3846 | http://dx.doi.org/10.21037/apm-20-1346
Annals of Palliative Medicine, Vol 10, No 4 April 2021 3837

Introduction in many ways and often include, but are not restricted to
“anxiety disorder” and “major depression” as defined by
For cancer patients entering into a palliative care (PC)
DSM IV-criteria. In the present study the term “anxiety and
setting, their quality of life (QOL) can be influenced
depressive symptoms” is used in a broad sense of the word.
by uncertainty, leading to psychological distress. This
As described, psychological distress in terminally ill
often causes additional suffering at the end of life (1).
patients is a serious problem with high prevalence in
Psychological distress can progress with physical decline
those showing symptoms of anxiety and depression. The
and worsening of symptoms (2,3). Anxiety and depressive
objectives of this study presented were (I) to screen for
symptoms are commonly reported to have a high
anxiety and depression using the validated German version
prevalence in advanced cancer patients. The prevalence
of the HADS (HADS-D) (21) in PC patients at admission
of depressive symptoms differs remarkably in different
to our palliative care unit (PCU), (II) to detect changes in
studies from 8% to 77% (1,4-9). About 50% of patients
anxiety and depression levels measured by the HADS-D
with advanced cancer meet the criteria for a psychiatric
at discharge from PCU as well as two weeks afterward at
disorder, the most common being adjustment disorders
home, and (III) to detect differences in the presence of
(11–35%) and major depression (5–26%) (10). Important
anxiety and depressive symptoms with respect to socio-
risk factors for the development of depression in cancer
demographic and clinical characteristics.
patients are previous depressive episodes in past medical
We present the following article in accordance with the
or family history (11), missing social support (12), younger
STROBE reporting checklist (available at http://dx.doi.
age, advanced disease at first diagnosis, bad functional
org/10.21037/apm-20-1346) (22).
status (13), or bad symptom control (14). Risk factors for
depression in PC patients are mostly unclear, but might
be similar. The end of life is often associated with worries Methods
and anxiety. The prevalence of anxiety in advanced cancer
Study design
patients ranges in different studies from 11% to 63% (4-9).
In addition, anxiety and depression have been shown to The PaRoLi study (Palliative Care in Rostock: Focus on
adversely affect QOL (8,9). Depression even has been Quality of Life) was conducted in a German PC cohort
found to be an independent predictor of poor survival in to screen for anxiety and depressive symptoms. The study
patients with advanced cancer (15). Nevertheless, low rates was designed as a prospective, longitudinal, cohort survey
of detection and treatment of psychological distress is still for consecutive patients in the interdisciplinary PCU of
a crucial problem in PC (16). In treatment of advanced Rostock University Medical Center and conducted in
cancer patients, both psychosocial and pharmacological accordance with the Declaration of Helsinki (as revised in
treatments are effective for anxiety and depression (10). 2013). The study was approved by the institutional ethics
Consequently, treating psychiatric conditions improves board of Rostock University Medical Center, Germany
QOL in these patients (10). Taking all this into account, (No.: A 2013-0028) and informed consent was taken from
screening for psychological distress should be an integral all the patients. The study design is displayed in Figure 1.
part of PC. To date, a variety of screening tools to Anxiety and depressive symptoms were assessed until 24 h
identify psychological morbidity in patients with somatic after admission (P1), within 24 h before discharge (P2) and
complaints are used. The Hospital Anxiety and Depression two weeks after discharge (P3) using the HADS-D.
Scale (HADS) is the most widely used instrument (7,17,18).
The HADS has been validated for many different patient
Patients
populations, as well as for PC patients (19,20). Professional
associations highly recommend the HADS based on From 5/2013 to 12/2013 consecutive PC patients were
objectivity, validity and reliability, including guidelines used enrolled. The last follow-up and closure of the database
for various somatic groups (21). A particular advantage was in 1/2015. All patients admitted to the PCU were
of this questionnaire is the relatively short length (2– screened. Patients eligible for study participation included
6 minutes) (18). those who were at least 18 years old and received PC. A
It should be noted that the terms “anxiety” and further eligibility criterion was the capability to understand
“depression” in these above mentioned studies are used and respond to study questionnaires in German. Exclusion

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(4):3836-3846 | http://dx.doi.org/10.21037/apm-20-1346
3838 Sewtz et al. Screening for anxiety and depression in PC cancer patients

Admission Assessed for eligibility Enrolled P1 (N=94) P2 (N=53) Discharge from PC unit P3 (N=29)
to PC unit (N=206) (N=102) admission + max. 24 h 24 h before discharge (N=72) discharge +14 d

Excluded from P2 (N=41) Excluded from P3 (N=43)

Excluded (N=104) Excluded from P1 (N=8) 29 died 18 no feedback
86 ineligible to participate 7 “14-day limit” 5 too ill 12 died
18 declined to participate 1 too ill 5 sudden transfer/discharge 5 too ill
1 withdrew consent 5 other
1 not completed 2 withdrew consent
1 no contact information

Figure 1 Study design of PaRoLi study. Anxiety and depression were assessed at three different time points: within 24 h after admission (P1),
within 24 h before discharge (P2) and two weeks after discharge (P3) using the HADS-D.

criteria were very bad general health condition, cognitive and specificity regarding a cut-off of ≥8 seems to be most
impairment without orientation, and a “14-day limit” for favorable for both scales (24). For better comparison with
interviews. The “14-day limit” was defined for re-admittances other studies, the cut-off ≥11 was also investigated. Besides,
within the study period: at least 14 days should lie between summing up of the anxiety and depression subscales, to
two interviews to reduce the burden of study participation. a global score, can be evaluated for unspecific screening
The questionnaires were completed either self-employed and progress, as anxiety and depressive symptoms develop,
or in a structured interview by the study team. For patients through common negative basic emotions. It can be used as
with minor cognitive impairment matching the inclusion a measure of the general mental distress in PC patients (19).
criteria, a form with all answer options in large writing was According to the original authors, a global score ≥16 is
provided. connected to a pronounced mental abnormality (17).

Data collection Statistical analysis

Age, sex, main diagnosis, type of cancer, time since Statistical evaluation was performed using IBM SPSS
diagnosis, symptoms and ECOG performance status at Statistics 22 for Windows. Results were obtained using
admission, length of stay, and place and time of death were descriptive statistics [frequency, mean value (MV), standard
recorded for each patient. Type of discharge (classified into deviation (SD) and median]. All quantitative characteristics
home, hospice, nursing home, other wards/hospital) as well were found to be non-normally distributed by the results
as concomitant specialized outpatient PC after discharge of Kolmogorov-Smirnov tests. In addition, survival time
was documented. analyses according to Kaplan-Meier were performed.
Survival was calculated between study inclusion and death
of the patient or closure of the database in 01/2015. The
Anxiety and depression (HADS-D)
test results of the HADS-D were calculated according
The 14-item questionnaire comprises of two seven-item to the instructions in the HADS-D manual (21). In the
subscales, measuring anxiety and depressive symptoms Kolmogorov-Smirnov test and Shapiro-Wilk test for normal
during the previous week (17), each item consisting of a distribution, all subscales and global scores were normally
4-point Likert scale. Total scores for each subscale were distributed except for the responses of the anxiety scale at
calculated. They can range from 0 to 21, with higher the first and second time points. Depending on the scales
scores indicating greater distress. Scores exceeding 10 on Wilcoxon signed rank test and paired t-test were applied to
each subscale constitute a case definition for psychological detect longitudinal changes. To identify factors influencing
morbidity, scores of 8–10 indicate sub-clinical caseness, the HADS-D results bivariate analyses (t-test or Mann-
and scores <8 represent non-cases respective to the original Whitney U test) were performed. To detect an influence of
authors (17). In PC studies different cut-off values are used the diagnosis the least significant difference (LSD) test was
(4,7,23). The following definition was applied: a score ≥8 applied. Concerning missing data we omitted those cases
indicates clinically meaningful anxiety or depression [9] with the missing data and analyzed the remaining. All P
as it has been shown that the balance between sensitivity values resulted from two-sided statistical tests and values of

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(4):3836-3846 | http://dx.doi.org/10.21037/apm-20-1346
Annals of Palliative Medicine, Vol 10, No 4 April 2021 3839

P<0.05 were considered to be statistically significant (22). depression scores) were completed during the study period.
Both, anxiety and depression screening scores were high
in the analyzed cohort. Seventy-eight point seven percent
Results
of all patients had at least once a significant level of anxiety
Study participation or depression (≥8) in one of the interviews, 50.0% at a
cut-off value of 11 respectively. As displayed in Figure 2
In the study period, 206 consecutive patients were screened
both mean sum scores showed little improvement during
for eligibility. One hundred and two patients were eligible
hospitalization (P=n.s.) but significant deterioration
and consented to take part in the study (see Figure 1), thus
between discharge and two weeks afterward [anxiety
the enrollment rate was 49.5%. Reasons for non-attendance
(P=0.046), depression (P=0.003)]. Overall, both sum scores
were death during the stay, rejection of consent, bad general
at P3 were higher than at P1 and P2 corresponding to
health condition, or sudden discharge.
an aggravation of anxiety and depressive symptoms. The
The phases of the study and reasons for non-participation
global score revealed the same trend (Table S1). In a further
are displayed in Figure 1. The actual participation rate for longitudinal analysis only patients for whom questionnaires
the first interview was 45.6% due to quick worsening of the were available for all three time points were analyzed
medical condition. Fifty-two percent of study patients took (Table 2). Results confirmed a similar symptom burden
part in the second interview. Of 41 sent questionnaires for overtime as the analysis of the total cohort at each time
the third interview, 29 were sent back (70.7%). In 78.2% point (Table S1). Overall, anxiety and depressive symptoms
inpatient surveys were performed in the form of structured were stable during the inpatient stay, but worsened
interviews, the other patients filled out the questionnaires significantly at home after two weeks. This was true for all
independently. patients as well as for those patients having completed all
three surveys as scheduled.
Patient characteristics and clinical course

Patient characteristics and data of the patients’ clinical Degree of anxiety and depressive symptoms
course are summarized in Table 1. The average age was Overall, anxiety (52.1%) was less prevalent than depression
expectedly high with a range from middle to high age. (73.4%), regarding (≥8) in one of the interviews. At
Most study patients had a cancer diagnosis. As time since baseline, as measured on the HADS-D anxiety was present
diagnosis might influence anxiety and depressive symptoms, in 40.9%, with depression in 56.7% of the patients. These
this variable was calculated. Patients knew their cancer rates increased over time with a relevant anxiety level in
diagnosis on average for two years. ECOG performance 44.8% and a clinically meaningful depression in 72.4% of
status was high: 65.7% of study participants had an ECOG the patients after discharge at home (Table S2). Hence,
3 or 4 when admitted to PCU. The mean stay was 8 days the proportion of conspicuous scores on both subscales
with a wide range. On average, patients were 3 days longer increased from P1 to P3. It can also be stated that the
in hospital than in PCU. In the study period, nearly a third proportion of abnormal values was higher in the outpatient
of the patients died in PCU, two thirds could be discharged than in the inpatient setting.
most commonly into home. After discharge about a third To identify factors potentially influencing anxiety
(21/72) received specialized outpatient palliative care and depressive symptoms, subsequent analyses were
(SOPC), for patients in home care the percentage was performed. Underlying cancer had no significant influence
37.5%. Mean survival after admission was 3.1 months, on the degree of anxiety (P1, P2, P3) and depression (P2,
median survival after admission was 1.1 months. As to be P3), although numbers were low (Table S3). However,
expected, 92.2% of patients deceased within follow-up. depression values on admission were heterogeneous based
Patients were most frequently married or in a partnership on the cancer type (P<0.05). As displayed in Figure 3
(65.5%), 57.6% were living at home with their family. abnormal depression scale values were more pronounced
in patients suffering from gastrointestinal and urogenital
cancers than patients with hematological or head-neck-
Anxiety and depression (HADS-D)
cancers. Age, gender, SOPC, or survival from admittance to
In total, 176 HADS-D questionnaires (174 anxiety, 176 the PCU did not influence the subscales in further analyses.

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(4):3836-3846 | http://dx.doi.org/10.21037/apm-20-1346
3840 Sewtz et al. Screening for anxiety and depression in PC cancer patients

Table 1 Demographic characteristics and clinical course of patients

Variable Number (N=102)

Sex (female), No. (%) 46 (45.2)

Mean age, yrs±SD 68.6±11.7

Median (min – max), yrs 71 [44–89]

Cancer, No. (%) 101 (99.0)

Urogenital 17 (16.8)

Hematological 15 (14.9)

Gastrointestinal 15 (14.9)

Hepatobiliary tract 13 (12.9)

Head-neck 10 (9.9)

Pulmonary 7 (6.9)

Pancreatic 6 (5.9)

Gynecological 6 (5.9)

Others 12 (11.9)

Mean time since first diagnosis, mths±SD (min. – max.) 23.8±31.4 (0.5–146.5)

ECOG at admission, No. (%)

ECOG 1 13 (12.7)

ECOG 2 22 (21.6)

ECOG 3 46 (45.1)

ECOG 4 21 (20.6)

Mean length of stay PCU, days±SD (min. – max.) 8±5 [1–22]

Death during current stay in PCU, No. (%) 30 (29.4)

Discharge from PCU, No. (%) 72 (70.6)

Type of discharge, No. (%)

Home 48 (66.7)

Hospice 10 (13.9)

Care facility 8 (11.1)

Other ward/hospital 6 (8.3)

Mean survival after admission, mths±SD (min. – max.) 3.1±4.8 (0.0–19.3)

Deceased within follow-up, No. (%) 94 (92.2)

In particular cancer patients knowing only shortly their symptoms, the length of stay was analyzed accordingly
cancer diagnosis benefited from inpatient PC. Patients with (Table S4). Patients who stayed one week or less in PCU
first diagnosis less than 365 days ago had higher anxiety and had significantly higher depression scores (P=0.032)
depression scores at admission and at home (P<0.05, both). at home. Accordingly, a longer stay on PCU was non-
The MVs are displayed in Table 3. significantly associated with less anxiety and depressive
Based on the assumption that longer stays in a PCU symptoms two weeks afterward.
might influence the degree of anxiety and depressive There was no significant difference between the results

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Annals of Palliative Medicine, Vol 10, No 4 April 2021 3841

P1 P2 P3
20 20 20
MV ± SD =7.11±3.32 MV ± SD =6.96±3.88 MV ± SD =8.00±4.57
18 N=9 18 N=52 18 N=29

16 16 16
14 14 14
12 12 12
Frequency

Frequency

Frequency
Anxiety 10 10 10
8 8 8
6 6 6
4 4 4
2 2 2
0 0 0
0 5 10 15 20 0 5 10 15 20 0 5 10 15 20
Anxiety score Anxiety score Anxiety score

P=0.679 P=0.046

20 20 20
MV ± SD =8.94±4.63 MV ± SD =8.98±4.64 MV ± SD =10.90±5.43
18 N=94 18 N=53 18 N=29

16 16 16
14 14 14
12 12 12
Frequency

Frequency

Frequency
Depression 10 10 10
8 8 8
6 6 6
4 4 4
2 2 2
0 0 0
0 5 10 15 20 0 5 10 15 20 0 5 10 15 20
Depression score Depression score Depression score

P=0.790 P=0.003

Figure 2 HADS-D sum scores according to time points. The HADS-D consists of two subscales, one for symptoms of anxiety and one
for symptoms of depression. Subscale scores range from 0, indicating no distress, to 21, indicating maximum distress; a score ≥8 indicates
clinically meaningful anxiety or depression. Numbers for each score are displayed. Significance analyses between time points (P1 vs. P2; P2
vs. P3) are shown.

Table 2 Longitudinal comparison: mean values of HADS-D subscales

P1–P2 P2–P3
Score P1 P2 P3
P value P value
Anxiety (N) 27 27 27
MV±SD 6.29±2.89 6.33±3.35 7.85±4.61 0.871 0.046

Median (min – max) 6 [2–12] 6 [0–14] 7 [1–17]

Depression (N) 27 27 27
MV±SD 8.32±4.48 8.54±4.52 11.11±5.46 0.779 0.003
Median (min – max) 8.5 [1–19] 8.5 [1–18] 10 [1–21]

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(4):3836-3846 | http://dx.doi.org/10.21037/apm-20-1346
3842 Sewtz et al. Screening for anxiety and depression in PC cancer patients

21
20
19
18
15
14
13
12
Depression score

11
10
9
8
7
6
5
4
3
2
1
0
Head-neck Hematological Gastrointestinal Urogenita
Cancer type

Figure 3 Depression scale (HADS-D/D) at admission. Individual depression scores on admission to PCU are shown according to the
underlying cancer type. The mean values (solid bars) and the HADS cut-off (dashed line) are displayed. PCU, palliative care unit.

Table 3 Mean values of HADS-D for cancer patients depending on time from initial diagnosis
P1 P2 P3 P1–P2 P2–P3
Score
MV ± SD MV ± SD MV ± SD P value P value

Anxiety

≥365 days 6.26±3.10 6.92±3.50 6.54±3.41 0.878 0.607

<365 days 7.95±3.42 8.06±4.35 10.00±4.97 0.900 0.172

P value 0.031 0.114 0.060

Depression

≥365 days 8.05±4.47 8.56±4.47 8.92±5.25 0.382 0.022

<365 days 10.16±4.75 10.67±4.86 13.60±4.79 0.732 0.256

P value 0.036 0.141 0.037

Global score

≥365 days 14.26±5.88 15.42±7.25 15.46±8.38 0.455 0.169

<365 days 18.12±7.06 18.72±8.01 23.60±9.41 0.891 0.128

P value 0.008 0.162 0.040

≥ initial diagnosis 365 days ago or longer (P1: N=43. P2: N=27. P3: N=13); < initial diagnosis less than 365 days ago (P1: N=43. P2: N=18.
P3: N=10).

of younger and older patients. However, the significant scores (Table S5).
deterioration from discharge to two weeks afterward was The same findings were made regarding the ECOG
only found among patients with higher age (>65). This was performance status. A higher ECOG score at admission
true for anxiety (P=0.021) and for depression (P=0.010) led to a more likely deterioration of anxiety (P=0.047)

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(4):3836-3846 | http://dx.doi.org/10.21037/apm-20-1346
Annals of Palliative Medicine, Vol 10, No 4 April 2021 3843

and depression (P=0.006) at home (Table S6). However, a that there is a high prevalence of anxiety and depressive
high ECOG score did not correlate with higher age >65 symptoms in men with prostate cancer (27) pointing as well
(P=0.268). at the need for support of these patients.
At discharge, anxiety levels had slightly improved and
depression scores remained at the same high level. These
Discussion
data indicate that anxiety and depressive symptoms can be
Here, we present the first study screening longitudinally for stabilized during a PCU visit. In contrast, Bužgová et al.
anxiety and depressive symptoms in a German PC cancer measured a significant deterioration in advanced cancer
patient cohort at three different time points: at admission to patients overtime during inpatient stay. This study was
a PCU, at discharge, and two weeks after discharge. Using conducted in an oncology department whereas our study
the HADS-D scores, it was demonstrated that anxiety took place in a PCU. In interventional studies, depression
and depressive symptoms were prevalent in this cohort scores could be improved by integrated inpatient PC
at unrecognized high levels. Very importantly we could (additional to transplant care) and aromatherapy massage in
identify that anxiety and depressive symptoms worsened a hospice setting (28,29).
shortly after discharge. To our knowledge no other study One of the most important findings of PaRoLi study
has measured this effect thus far. is the fact that following discharge anxiety and depressive
At admission to PCU 41% of the 94 patients had symptoms deteriorate significantly after short period of
clinically meaningful anxiety and 57% had relevant time. Studies by Lloyd-Williams et al. have shown that
depression scores, demonstrating the high prevalence. in an outpatient setting PC cancer patient depression
Consequently, anxiety levels were lower than depression scores remain largely stable (15,30). Other outpatient PC
levels. These results are in line with other studies: Holtom studies showed lower HADS scores (4,23,31). However,
and Barraclough [2000] state that in PC patients, anxiety these patients were mostly early PC patients. To our
is less frequent than depression. They found depression knowledge, no other non-interventional study has analyzed
in 56% of patients, of whom 28% had relevant anxiety psychological distress in a PC cohort longitudinally after
levels (18). Renom-Guiteras et al. screened prospectively discharge home. Whereas for cancer patients no specialized
in 61 PC cancer inpatients and showed a depression level outpatient teams exist, this is the case for PC. In Germany,
of 62% and an anxiety level of 54% (25). Another study specialized outpatient PC teams exist consisting of nurses
of Teunissen et al. showed possible depression in 56% and and doctors visiting patients at home to alleviate symptom
possible anxiety in 34% of 79 hospitalized advanced cancer burden. Our study was not powered to detect beneficial
patients (6). Bužgová et al. studied 225 cancer patients effects of SOPC and due to low numbers we couldn’t
receiving PC in an oncology department and found anxiety detect differences in patients receiving SOPC. Other
to be present in 34% and depression in 48% of patients (9). studies showed beneficial effects of SOPC (not focusing on
In contrast, Austin et al. [2011] found anxiety and depression) (32). More research is needed to study the effect
depression in only 20% of PC patients without significant of SOPC on psychological distress.
difference between PC inpatients and those receiving PC Performing studies in a PC patient cohort is very
at home (4). difficult due to the medical conditions of the patients in
Of note, underlying cancer disease significantly this situation. The recruitment of study individuals from
influenced depression scores. Whereas hematological and a limited number of often severely burdened patients in
head-neck cancer patients had lower depression scores, end of life care is a major challenge. Almost 15% of the
gastrointestinal and urogenital cancer patients had higher palliative patients died within 24 hours after admission.
depression scores, at least at admission. There were no Due to this vulnerability, we decided to screen only
differences in regards to anxiety, although patient numbers with HADS-D for anxiety and depression. The PaRoLi
were low. It can be stated that each patient population study was a non-randomized, single-center prospective
has specific needs. This has been shown in a randomized study. Nevertheless, a large, consecutive patient number
clinical trial by Temel et al. (26) amongst other studies. In was screened—representing an unselected PC inpatient
their study, early integrated PC improved QOL and mood cohort. Participants of our study were almost exclusively
in patients with incurable cancers but patient outcomes advanced cancer patients. This corresponds to other
varied by cancer type. In addition, a meta-analysis revealed PC studies (4,18,25). Moreover, data from the German

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(4):3836-3846 | http://dx.doi.org/10.21037/apm-20-1346
3844 Sewtz et al. Screening for anxiety and depression in PC cancer patients

Hospice and Palliative Care Evaluation, a national long- Footnote

term quality assurance project providing information on
Reporting Checklist: The authors have completed the
PC patients, showed that 92% of PC patients in Germany
STROBE reporting checklist. Available at http://dx.doi.
suffer from cancer (33). So, our study cohort can be seen as
org/10.21037/apm-20-1346
representative for a German PC cohort.
The overall participation rate was 49.5%. Other
Data Sharing Statement: Available at http://dx.doi.
prospective studies in PC report participation rates ranging
org/10.21037/apm-20-1346
from 28% to 74% (25,34-36). As expected, participation
decreased over time due to quickly deteriorating functional
Conflicts of Interest: All authors have completed the ICMJE
status, pointing at the difficulties to perform longitudinal
uniform disclosure form (available at http://dx.doi.
studies in a PC cohort. About one third of the patients
org/10.21037/apm-20-1346). CJ serves as an unpaid
died during PC stay. A limitation is the selection bias.
editorial board member of Annals of Palliative Medicine from
Many patients stopped participating or refused initially to
Jan 2019 to Dec 2021. The other authors have no conflicts
participate due to fatigue or pain. There was no assessment,
of interest to declare.
when these patients got better during inpatient stay, because
later enrollment was not part of the protocol. Thus, the Ethical Statement: The authors are accountable for all
overall picture may even be too positive. This bias may be aspects of the work in ensuring that questions related
circumvented by multiple study enrollments in subsequent to the accuracy or integrity of any part of the work are
studies. appropriately investigated and resolved. The study was
conducted in accordance with the Declaration of Helsinki (as
Conclusions revised in 2013). The study was approved by institutional
ethics board of Rostock University Medical Center,
In essence, our study points out that discharge and the time Germany (No.: A 2013-0028) and informed consent was
after discharge are crucial for the patients and interventions taken from all the patients.
may have to be explored. This observation was particularly
pronounced in patients with recent cancer diagnosis being Open Access Statement: This is an Open Access article
probably still in the process of coping. Other negatively distributed in accordance with the Creative Commons
influencing factors were poor performance score and higher Attribution-NonCommercial-NoDerivs 4.0 International
age. Our results integrate into existing data and demonstrate License (CC BY-NC-ND 4.0), which permits the non-
that patients with progressed disease often suffer from commercial replication and distribution of the article with
anxiety and depressive symptoms. the strict proviso that no changes or edits are made and the
In conclusion, the PaRoLi study adds important aspects original work is properly cited (including links to both the
of incurable cancer patient care. Anxiety and depressive formal publication through the relevant DOI and the license).
symptoms should be screened for regularly in all PC See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
patients, in particular after discharge from an inpatient
setting. Future studies will have to address the potential
References
beneficial effects of discharge.
1. Block SD. Assessing and managing depression in the
terminally ill patient. ACP-ASIM End-of-Life Care
Acknowledgments
Consensus Panel. American College of Physicians -
First and foremost, we thank the patients who participated American Society of Internal Medicine. Ann Intern Med
in this study. Moreover, we would like to express our 2000;132:209-18.
gratitude to all staff of the palliative care unit of Rostock 2. Morasso G, Capelli M, Viterbori P, et al. Psychological
University Medical Center for their dedicated work and and symptom distress in terminal cancer patients with met
their ongoing willingness to help within this project. and unmet needs. J Pain Symptom Manage 1999;17:402-9.
Funding: None. 3. Gruneir A, Smith TF, Hirdes J, et al. Depression in

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(4):3836-3846 | http://dx.doi.org/10.21037/apm-20-1346
Annals of Palliative Medicine, Vol 10, No 4 April 2021 3845

patients with advanced illness: an examination of Ontario 17. Zigmond AS, Snaith RP. The Hospital Anxiety and
complex continuing care using the Minimum Data Set 2.0. Depression Scale. Acta Psychiatr Scand 1983;67:361-70.
Palliat Support Care 2005;3:99-105. 18. Holtom N, Barraclough J. Is the Hospital Anxiety and
4. Austin P, Wiley S, McEvoy PM, et al. Depression and Depression Scale (HADS) useful in assessing depression in
anxiety in palliative care inpatients compared with those palliative care? Palliat Med 2000;14:219-20.
receiving palliative care at home. Palliat Support Care 19. Lloyd-Williams M. Screening for depression in palliative
2011;9:393-400. care patients: a review. Eur J Cancer Care (Engl)
5. Delgado-Guay M, Parsons HA, Li Z, et al. Symptom 2001;10:31-5.
distress in advanced cancer patients with anxiety and 20. Mitchell AJ, Meader N, Symonds P. Diagnostic validity
depression in the palliative care setting. Support Care of the Hospital Anxiety and Depression Scale (HADS)
Cancer 2009;17:573-9. in cancer and palliative settings: a meta-analysis. J Affect
6. Teunissen SCCM, Graeff A, Voest EE, et al. Are anxiety Disord 2010;126:335-48.
and depressed mood related to physical symptom burden? 21. Herrmann-Lingen C, Buss U, Snaith RP. Hospital Anxiety
A study in hospitalized advanced cancer patients. Palliat and Depression Scale - Deutsche Version (HADS-D) (3.,
Med 2007;21:341-6. aktualisierte und neu normierte Aufl.). Bern: Verlag Hans
7. Hotopf M, Chidgey J, Addington-Hall J, et al. Depression Huber, 2011.
in advanced disease: A systematic review. Part 1: Prevalence 22. von Elm E, Altman DG, Egger M, et al. The
and case finding. Palliat Med 2002;16:81-97. Strengthening the Reporting of Observational Studies
8. Smith EM, Gomm SA, Dickens CM. Assessing the in Epidemiology (STROBE) statement: guidelines
independent contribution to quality of life from anxiety for reporting observational studies. J Clin Epidemiol
and depression in patients with advanced cancer. Palliat 2008;61:344-9.
Med 2003;17:509-13. 23. Temel JS, Greer JA, Muzikansky A, et al. Early palliative
9. Bužgová R, Jarošová D, Hajnová E. Assessing anxiety and care for patients with metastatic non-small-cell lung
depression with respect to the quality of life in cancer cancer. N Engl J Med 2010;363:733-42.
inpatients receiving palliative care. Eur J Oncol Nurs 24. Bjelland I, Dahl AA, Haug TT, et al. The validity of
2015;19:667-72. the Hospital Anxiety and Depression Scale. An updated
10. Miovic M, Block S. Psychiatric disorders in advanced literature review. J Psychosom Res 2002;52:69-77.
cancer. Cancer 2007;110:1665-76. 25. Renom-Guiteras A, Planas J, Farriols C, et al. Insomnia
11. Burcusa SL, Iacono WG. Risk for recurrence in among patients with advanced disease during admission in
depression. Clin Psychol Rev 2007;27:959-85. a Palliative Care Unit: a prospective observational study on
12. Rodin G, Walsh A, Zimmermann C, et al. The its frequency and association with psychological, physical
contribution of attachment security and social support to and environmental factors. BMC Palliat Care 2014;13:40.
depressive symptoms in patients with metastatic cancer. 26. Temel JS, Greer JA, El-Jawahri A, et al. Effects of Early
Psychooncology 2007;16:1080-91. Integrated Palliative Care in Patients With Lung and
13. Lo C, Zimmermann C, Rydall A, et al. Longitudinal GI Cancer: A Randomized Clinical Trial. J Clin Oncol
study of depressive symptoms in patients with 2017;35:834-41.
metastatic gastrointestinal and lung cancer. J Clin Oncol 27. Watts S, Leydon G, Birch B, et al. Depression and anxiety
2010;28:3084-9. in prostate cancer: a systematic review and meta-analysis
14. Rayner L, Lee W, Price A, et al. The clinical epidemiology of prevalence rates. BMJ Open 2014;4:e003901.
of depression in palliative care and the predictive value of 28. El-Jawahri A, Traeger L, Greer JA, et al. Effect of
somatic symptoms: cross-sectional survey with four-week Inpatient Palliative Care During Hematopoietic Stem-
follow-up. Palliat Med 2011;25:229-41. Cell Transplant on Psychological Distress 6 Months After
15. Lloyd-Williams M, Shiels C, Taylor F, et al. Depression- Transplant: Results of a Randomized Clinical Trial. J Clin
-an independent predictor of early death in patients with Oncol 2017;35:3714-21.
advanced cancer. J Affect Disord 2009;113:127-32. 29. Soden K, Vincent K, Craske S, et al. A randomized
16. Irwin SA, Rao S, Bower K, et al. Psychiatric issues in controlled trial of aromatherapy massage in a hospice
palliative care: recognition of depression in patients setting. Palliat Med 2004;18:87-92.
enrolled in hospice care. J Palliat Med 2008;11:158-63. 30. Lloyd-Williams M, Riddleston H. The Stability of

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(4):3836-3846 | http://dx.doi.org/10.21037/apm-20-1346
3846 Sewtz et al. Screening for anxiety and depression in PC cancer patients

Depression Scores in Patients Who Are Receiving 34. Minagawa H, Uchitomi Y, Yamawaki S, et al. Psychiatric
Palliative Care. J Pain Symptom Manage 2002;24:593-7. morbidity in terminally ill cancer patients: a prospective
31. Götze H, Brähler E, Gansera L, et al. Psychological study. Cancer 1996;78:1131-7.
distress and quality of life of palliative cancer patients and 35. Le Fevre P, Devereux J, Lawrie SM, et al. Screening for
their caring relatives during home care. Support Care psychiatric illness in the palliative care inpatient setting: a
Cancer 2014;22:2775-82. comparison between the Hospital Anxiety and Depression
32. Groh G, Vyhnalek B, Feddersen B, et al. Effectiveness of a Scale and the General Health Questionnaire-12. Palliat
specialized outpatient palliative care service as experienced Med 1999;13:399-407.
by patients and caregivers. J Palliat Med 2013;16:848-56. 36. Bakitas M, Lyons KD, Hegel MT, et al. Effects of a
33. Hess S, Stiel S, Hofmann S, et al. Trends in specialized palliative care intervention on clinical outcomes in patients
palliative care for non-cancer patients in Germany--data with advanced cancer: the Project ENABLE II randomized
from the national hospice and palliative care evaluation controlled trial. JAMA 2009;302:741-9.
(HOPE). Eur J Intern Med 2014;25:187-92.

Cite this article as: Sewtz C, Muscheites W, Grosse-Thie C,

Kriesen U, Leithaeuser M, Glaeser D, Hansen P, Kundt G,
Fuellen G, Junghanss C. Longitudinal observation of anxiety
and depression among palliative care cancer patients. Ann
Palliat Med 2021;10(4):3836-3846. doi: 10.21037/apm-20-1346

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2021;10(4):3836-3846 | http://dx.doi.org/10.21037/apm-20-1346
 Supplementary

Table S1 Longitudinal comparison: mean values of HADS-D subscales (all questionnaires)

P1 P2 P3 P1–P2 P2–P3
Score
MV ± SD MV ± SD MV ± SD P-value P-value

Anxiety (N) (93) (52) (29)

MV ± SD 7.11 ± 3.32 6.96 ± 3.88 8.00 ± 4.57 0.679 0.046

median (min – max) 7 (0 - 15) 6 (0 - 19) 7 (1 - 17)

Depression (N) (94) (53) (29)

MV ± SD 8.94 ± 4.63 8.98 ± 4.64 10.90 ± 5.43 0.790 0.003

Median (min– max) 9 (0 – 21) 9 (1 – 21) 10 (1 - 21)

Global score (N) (93) (52) (29)

MV ± SD 16.03 ± 6.64 15.92 ± 7.67 18.90 ± 9.66 0.950 0.005

Median (min– max) 16 (3 – 34) 16 (3 – 37) 17 (2 – 38)

Table S2 Symptom burden at each time point

Score P1 P2 P3

Anxiety ≥ 11 – no. (%) 14 (15.1%) 9 (17.3%) 9 (31.0%)

Depression ≥ 11 – no. (%) 31 (33.0%) 18 (34.0%) 13 (44.8%)

Anxiety or depression ≥ 11 – no. (%) 34 (36.2%) 21 (39.6%) 13 (44.8%)

Anxiety ≥ 8 – no. (%) 38 (40.9%) 19 (36.5%) 13 (44.8%)

Depression ≥ 8 – no. (%) 56 (59.6%) 34 (64.2%) 21 (72.4%)

Anxiety or depression ≥ 8 – no. (%) 65 (69.1%) 36 (67.9%) 21 (72.4%)

Table S3 HADS-D depression scale according to cancer type

Cancer localization Number (N) Depression score at admission to PCU (MV ± SD)

Head-neck-cancer 10 6.00 ± 2.87

Hematological cancer 14 6.57 ± 4.82

Gastrointestinal cancer 15 9.93 ± 4.43

Urogenital cancer 17 10.06 ± 5.33

© Annals of Palliative Medicine. All rights reserved. http://dx.doi.org/10.21037/apm-20-1346

 Table S4 HADS-D scores depending on the length of stay in the PCU
P1 P2 P3 P1–P2 P2–P3
Score
MV ± SD MV ± SD MV ± SD P-value P-value

Anxiety

PCU ≤ 7 7.42 ± 3.17 6.57 ± 2.50 9.44 ± 4.50 0.277 0.059

PCU > 7 6.74 ± 3.48 7.28 ± 4.72 6.23 ± 4.15 0.688 0.372

P-value 0.310 0.956 0.059

Depression

PCU ≤ 7 8.90 ± 3.96 10.21 ± 3.82 12.81 ± 4.40 0.443 0.047

PCU > 7 8.98 ± 5.33 7.97 ± 5.05 8.54 ± 5.80 0.805 0.023

P-value 0.936 0.079 0.032

Global score

PCU ≤ 7 16.32 ± 5.97 16.78 ± 5.69 22.25 ± 8.59 0.867 0.033

PCU > 7 15.70 ± 7.40 15.24 ± 8.98 14.77 ± 9.53 0.959 0.090

P-value 0.655 0.477 0.038

≤ length of stay one week or less PCU (P1: N = 50. P2: N = 35. P3: N = 18); > length of stay more than one week PCU (P1: N = 43. P2: N =
29. P3: N = 13)

Table S5 HADS-D scores depending on age

P1 P2 P3 P1–P2 P2–P3
Score
MV ± SD MV ± SD MV ± SD P-value P-value

Anxiety

≤ 65 7.63 ± 3.28 7.68 ± 3.42 7.82 ± 4.58 0.429 0.865

> 65 6.75 ± 3.32 6.55 ± 4.12 8.11 ± 4.69 0.929 0.021

P-value 0.223 0.227 0.870

Depression

≤ 65 8.24 ± 4.68 8.85 ± 4.48 9.91 ± 6.46 0.593 0.169

> 65 9.41 ± 4.57 9.06 ± 4.80 11.50 ± 4.79 0.969 0.010

P-value 0.232 0.874 0.454

Global score

≤ 65 15.87 ± 6.56 16.47 ± 7.37 17.73 ± 10.77 0.884 0.556

> 65 16.15 ± 6.75 15.61 ± 7.94 19.61 ± 9.17 0.892 0.004

P-value 0.844 0.693 0.619

≤ 65 years or younger (P1: N = 38. P2: N = 19. P3: N = 11); > older than 65 years (P1: N = 55. P2: N = 33. P3: N = 18)

© Annals of Palliative Medicine. All rights reserved. http://dx.doi.org/10.21037/apm-20-1346

 Table S6 HADS-D scores depending on ECOG performance status
P1 P2 P3 P1–P2 P2–P3
Score
MV ± SD MV ± SD MV ± SD P-value P-value

Anxiety

ECOG 1-2 6.41 ± 3.00 6.38 ± 3.29 7.27 ± 4.41 0.526 0.473

ECOG 3-4 7.48 ± 3.43 7.35 ± 4.24 8.44 ± 4.73 0.241 0.047

P-value 0.130 0.547 0.513

Depression

ECOG 1-2 8.53 ± 4.95 9.09 ± 4.59 9.00 ± 4.54 0.853 0.276

ECOG 3-4 9.15 ± 4.48 8.90 ± 4.74 12.06 ± 5.71 0.578 0.006

P-value 0.545 0.886 0.144

Global score

ECOG 1-2 14.94 ± 6.96 15.43 ± 6.93 16.27 ± 8.74 0.890 0.208

ECOG 3-4 16.61 ± 6.45 16.26 ± 8.23 20.50 ± 10.08 0.809 0.011

P-value 0.251 0.706 0.260

ECOG 1 or 2 (P1: N = 32. P2: N = 21. P3: N = 11); ECOG 3 or 4 (P1: N = 61. P2: N = 31. P3: N = 18)

© Annals of Palliative Medicine. All rights reserved. http://dx.doi.org/10.21037/apm-20-1346