Major depressive disorder (MDD) (American Psychiatric Association, 1994) is associated
with an increased symptom burden, greater disability, reduced quality of life and
poorer medical outcome (Katon, 1996), and occurs in a substantial proportion of cancer
patients (Lynch, 1995; McDaniel et al, 1995). There is some evidence for the efficacy
of antidepressant drugs (McDaniel et al, 1995) and for psychological therapies (Sheard
and Maguire, 1999). However, many patients do not receive any potentially effective
treatment (Lynch, 1995). We have therefore developed and piloted a cancer nurse-delivered
intervention. The aim of this study was to perform a preliminary evaluation of its
feasibility and efficacy in oncology outpatients.
MATERIALS AND METHODS
Patients and recruitment
We recruited patients with MDD from consecutive attenders at breast, gynaecological,
bladder, prostate, testicular and colorectal clinics at the Edinburgh Cancer Centre
between September 1999 and September 2000 using a screening procedure described in
the companion paper (Sharpe et al, 2003).
Patients were excluded if: (a) the oncologist predicted that they would not survive
to follow-up or if they had (b) a complicating and uncontrolled medical problem, (c)
a complicating major psychiatric diagnosis, (d) a history of continuous depression
for more than 1 year prior to cancer diagnosis, (e) difficulty in communicating and
(f) were currently receiving active specialist treatment from a psychologist or psychiatrist.
When patients were excluded, their doctors were told of their diagnosis of MDD.
Design and power
The study was a nonrandomised comparison of the outcome of two sequentially recruited
cohorts. To detect a difference in the proportions of patients still meeting the criteria
for MDD of the magnitude size previously reported in a similar study in primary-care
patients (35%) (Katon et al, 1996) using a paired analysis, approximately 56 cases
(28 in each of the treatment and usual care groups) are required (80% power and significance
level of 0.05).
MEASURES
Baseline measures
Demographic and cancer data: These were collected from medical records.
Structured Clinical Interview for DSM-IV (SCID)
The presence of MDD and depressive symptoms was determined during telephone interview
using the SCID (First et al, 1999). All symptoms counted toward the diagnosis and
no judgements were made about their aetiology. Telephone SCID has good agreement with
a face-to-face interview (Cacciola et al, 1999), and is acceptable to patients (Allen
et al, 2003).
Hospital Anxiety and Depression Scale (HADS) (Zigmond and Snaith, 1983): Anxiety and
depressive symptoms were assessed with this 14-item self-rated scale designed for
use in the medically ill (see companion paper Sharpe et al, 2003).
Manchester Concerns Checklist (Harrison et al, 1994): Patient's concerns were rated
using this 14-item checklist, each concern being rated on a five-point scale from
‘not a worry’ to ‘extremely worried’.
Outcome measures
The primary outcome measure was the presence of MDD according to DSM-IV criteria as
assessed by the SCID interview and determined from audiotapes and/or notes of the
interviews by a consultant psychiatrist (MS) blind to the patient's treatment status.
The number of MDD symptoms on the SCID and self-rated scales listed above were secondary
outcome measures.
Definition of adequate dose of antidepressant drugs
We defined the adequacy of the dose of antidepressant drugs as that specified in the
British National Formulary (www.bnf.org), but accepting 75 mg as effective for tricyclic
antidepressants (Furukawa et al, 2002).
Treatment conditions
Usual care alone
We told the GP, oncologist and the patient about the diagnosis of MDD and the GP was
asked to ‘manage the patient as they normally would’.
Usual care plus the experimental intervention
These patients also received the nurse-delivered intervention, which comprised:
Education about depression (e.g. that the symptoms of depression were a separate problem
from the cancer and of the probable effectiveness of treatment).
Up to ten 30-min sessions of problem-solving therapy intended to help patients to
take a positive and systematic approach to tackling their problems (Wood and Mynors-Wallis,
1997).
Patients were encouraged, within the context of problem solving, to consider seeing
their GP to discuss antidepressant therapy. Although prescribing was left to the GP,
the nurse ensured that if taken, a therapeutic dose of antidepressant was attained
and adhered to.
Coordinating and monitoring the patient's treatment with respect to the MDD.
The cancer nurse received 6 months training in the intervention and was rated as competent
on the basis of videotape recordings of treatment. She received weekly supervision
from a consultant psychiatrist during the trial. Treatment sessions took place weekly
in the hospital or where necessary at home or by telephone. After treatment, patients
were told that they could contact the nurse for ‘booster’ sessions.
Procedure
All participating patients gave written consent.
Allocation to treatment
We assigned patients recruited between 1999 and February 2000 to usual care only and
those recruited from March 2000 to August 2000 to the additional intervention.
Follow-up
Outcome assessments were at 3 and 6 months by telephone interview and postal self-report
questionnaires. At the end of the study period, GPs were notified if their patient
still had MDD.
Statistical analysis
Matching of the groups was by individual baseline variables in the following order:
sex, age (10-year bands), presence of active disease and cancer site. The statistical
analysis was appropriate for matched pairs. The McNemar test was used to compare proportions
and paired t-tests to compare means. All tests were two-tailed.
Ethical approval
Lothian Research Ethics Committee approved the study.
RESULTS
Patients and recruitment
We identified 196 patients with MDD by screening. Seven refused further assessment
and 39 were ineligible (20 because of chronic depression and 19 for other reasons).
Nonparticipation among those approached was 31of 83 (37%) for usual care and 34 of
64 (53%) for the additional intervention. The reasons given were time, distance and
a preference not to discuss emotional matters. The participating clinicians were positive
about the intervention.
Matching of groups
After matching 30 usual care only patients to the 30 receiving the intervention, there
were no substantial or statistically significant differences between groups on demographic,
cancer or psychological variables (see Tables 1
Table 1
Demographic and characteristics of depression of the matched groups at baseline
Number (percentage) unless otherwise specified
Intervention (n=30)
Usual care (n=30)
Demographics
Mean age in years (standard deviation)
58 (10.6)
56 (10.5)
Female
28 (93.3)
28 (93.3)
Depression
Median duration (months) of episode (range)
7 (1–120)
7 (1–96)
Depression onset in relation to cancer
With diagnosis
7 (23.3)
10 (33.3)
With recurrence
3 (10)
2 (6.7)
After diagnosis/recurrence
20 (66.7)
18 (60)
Self reported previous depression
No previous episodes
15 (50)
17 (56.7)
Prescribed antidepressant agent for this episode
15 (50)
5 (16.7)
Currently taking a therapeutic dose of an antidepressant agenta
5 (16.7)
3 (10)
Previously received psychological therapyb
5 (16.7)
1 (3.3)
Previously used other support servicesc
3 (10)
3 (10)
Cancer
Median time (years) since diagnosis (range)
4 (0–19)
3 (0–29)
Site
Breastd
26 (87)
27 (90)
Disease state
No active disease
24 (80)
24 (80)
Local disease
2 (7)
2 (7)
Metastases
4 (13)
4 (13)
Treatment stage
Active treatmente
8 (27)
2 (7)
a
Defined in methods.
b
Consulted a psychiatrist/psychologist.
c
Other supportive services – breast care nurse, occupational health-care nurse, counsellor,
faith-healer and non-NHS charitably funded cancer support centre.
d
ther sites were the bladder, prostate, colorectal, thyroid and ovary.
e
Long-term hormonal-based therapies such as tamoxifen not included as active treatment.
and 2
Table 2
Primary and secondary outcome variables at baseline 3 and 6 months
Time
No. pairs
Intervention
Usual care only
Mean difference (95% CI)
t
Sig. (P-value)
Interview (SCID)
No MDD*
Baseline
30
0
0
3 months
28
71 (20)
32 (9)
39.3 (7.9–56)
0.01
6 months
26
81 (22)
42 (11)
38.5 (5.4–57)
0.02
Number of MDD symptoms
Baseline
30
6.4 (1.2)
6.5 (1.3)
0 (−0.7–0.5)
0.3
0.74
3 months
28
3.1 (2.4)
5.5 (2.2)
2.3 (−3.6–−1.1)
3.8
0.001
6 months
26
2.6 (2.3)
4.9 (2.2)
2.2 (−3.8––0.7)
3.0
0.006
Self-Rated Scales
HADS anxiety
Baseline
30
12.9 (3.1)
12.8 (3.6)
0 (−1.9–2.0)
0.04
0.97
3 months
27
7.7 (4.1)
12.6 (3.6)
4.8 (−7.1–−2.6)
4.3
0.000
6 months
26
7.9 (4.7)
11.7 (3.7)
3.8 (−6.6–−0.9)
2.7
0.012
HADS depression
Baseline
30
10.4 (3.6)
10.3 (4.0)
0 (−1.8–2.0)
0.71
0.94
3 months
27
7.0 (4.4)
10.6 (3.7)
3.5 (−5.9–−1.1)
3.02
0.006
6 months
26
7.0 (4.1)
9.6 (4.7)
2.7 (−5.5–0.1)
1.96
0.061
Number of concerns
Baseline
30
6.7 (3.5)
6.7 (3.1)
0 (−1.7–1.6)
0.04
0.97
3 months
28
3.9 (4.1)
6.0 (3.7)
2.4 (−4.5–−0.2)
2.3
0.03
6 months
25
3.3 (3.9)
5.7 (4.1)
2.2 (−4.7–0.34)
1.8
0.09
Outcomes expressed as percentages and percentage differences for pairs, and means
and mean differences for pairs, with confidence intervals. Statistical significance
by paired t-tests and McNemar test*. [2]All means and (s.d.) except*, which are percentages
(numbers). CI=confidence intervals; SCID=Structured Clinical Interview for DSM-IV;
MDD=major depressive disorder; HADS=Hospital Anxiety and Depression Scale.
). Most had breast cancer and were in a postacute treatment phase. A greater number
of patients in the intervention group had received antidepressant drugs prior to recruitment,
but only a very small and similar number were taking a therapeutic dose.
Missing outcome data
Data on the principal outcome was available on 28 pairs at 3 months and 26 pairs at
6 months (four patients died and two were lost to follow-up). There was a small amount
of additional missing data on secondary measures due to noncompletion of questionnaires.
Intervention received
Problem-solving therapy
Every patient in the intervention group had an initial assessment, plus between 1
and 13 weekly problem-solving sessions (mean 7.3, s.d. 2.0) of approximately 30 min
duration. The duration of treatment ranged from 2 to 16 weeks. Only six patients requested
post-treatment ‘booster’ sessions. Only four sessions were conducted at the patients'
home and very few by telephone. The treating nurse spent a mean of 6 h with each patient
and an additional 4 h on administration, calls to GPs, travel and supervision. The
psychiatrist provided 1 h of supervision per week and attended treatment sessions
on four occasions. The total time spent per patient treated was therefore approximately
10 h for the nurse and 1 h for the psychiatrist.
Antidepressant medication
During the 6-month study period, most (27 of 30; 90%) of the patients in the intervention
group were prescribed an antidepressant by their GP, although only 16 (53%) attained
a therapeutic dose, largely because of the poor tolerance of side effects. In comparison,
only half (16 of 30; 53%) of the patients in the usual care only group were prescribed
an antidepressant drug and only (23%) attained a therapeutic dose.
Other treatments received
One patient in the treatment group and four patients in the usual care only group
saw a psychologist or psychiatrist during the study period. A small number of patients
in each group saw other counsellors.
Outcome data
Principal outcome
Table 2 shows the percentage of patients who no longer met the criteria for MDD at
3 and 6 months and the number of symptoms of MDD elicited on the SCID interview. There
was a substantially and statistically significantly greater improvement in the intervention
group at both time points.
Secondary outcomes
Table 2 also shows the substantial and statistically significantly greater reductions
in the self-rated secondary outcomes, which were greatest at 3 months and largely
but not entirely maintained at 6 months.
DISCUSSION
Main findings
This preliminary comparison of the nurse-delivered intervention with usual care suggests
that it is feasible to train a nurse, to deliver the intervention (although with a
high patient refusal rate – see below) and to gain the cooperation of clinicians.
It also produces a substantially better outcome for patients. The beneficial effect
is apparent at the end of the active treatment phase (3 months) and is largely maintained
at the follow-up point (6 months).
Limitations
Nonrandomised comparisons can overestimate the differences between treatments (Altman
and Bland, 1999). There was a relatively low participation rate, although surprisingly,
this was not much higher in those offered usual care only than in those asked to participate
in the much more time-consuming treatment intervention. The main reason for this is
probably that patients were recruited by screening rather than referral. An intervention
study for depression after myocardial infarction reported similar findings (Frasure-Smith
et al, 1997). Participants were predominantly females with inactive breast cancer,
limiting the generalisability of the findings. The sample was small leading to wide
confidence intervals around the results. Finally, as a single nurse administered the
intervention, we cannot conclude that cancer nurses in general could necessarily be
trained to deliver the treatment effectively.
Other studies
Oncologists miss many cases of depression (Fallowfield et al, 2001). However, simply
feeding back the findings of screening does not seem to help (McLachlan et al, 2001).
We therefore need to not only improve the identification of depression but also the
provision of treatment. Specialist psychiatrists and psychologists are in short supply.
One potential solution that requires further evaluation is for the medical and nursing
oncology staff to play a greater role (Stiefel et al, 2001). It is therefore surprising
that there have been few trials of cancer nurse delivered interventions for depression.
Early studies found that simple counselling by specialist nurses did not prevent depression,
but that better recognition and subsequent treatment by a psychiatrist improved outcome
(Maguire et al, 1980; Maguire et al, 1985). We are not aware of any previous studies
of the management of established MDD comorbid with cancer by oncology nurses or other
oncology clinic staff.
Implications
The results of this preliminary study indicate that depression management systems
that combine screening and intervention are worthy of further development and evaluation
in randomised trials.
FUNDING
The NHS Research and Development/Cancer Research Campaign (now Cancer Research UK)
Cancer Research Programme funded this study.