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General Hospital Psychiatry 25 (2003) 158 –168
Improving primary care treatment of depression among patients with
diabetes mellitus: the design of the Pathways Study
Wayne Katon, M.D. a, *, Michael Von Korff, ScD. b , Elizabeth Lin, M.D., M.P.H. b ,
Greg Simon, M.D., M.P.H. b , Evette Ludman, Ph.D. b , Terry Bush, Ph.D. b , Ed Walker, M.D. a ,
Paul Ciechanowski, M.D., M.P.H. a , Carolyn Rutter, Ph.D. b
a Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195– 6580, USA
b Center for Health Studies, Group Health Cooperative, Psychiatry Service, University Hospital, Seattle, WA 98195– 6580, USA
This paper describes the methodology of a population based study of primary care patients with diabetes mellitus enrolled in a health
maintenance organization. The first goal was to determine the prevalence and impact of depression in patients with diabetes. The second
goal was to randomize approximately 300 patients with diabetes and major depression and/or dysthymia in a trial to test the effectiveness
of a collaborative care intervention in improving quality of care and health outcomes among patients with diabetes and depression. © 2003
Elsevier Inc. All rights reserved.
1. Introduction
Both major depression and depressive symptoms have been
shown in most studies to be associated with glucose dysregu-
lation [6 – 8]. This may either be due to the adverse impact of
depression on diabetes self-care (i.e., diet, exercise, checking
blood glucose, and taking medications), [6 – 8] direct adverse
physiologic effects on glucose metabolism, [9] or a combina-
tion of these two mechanisms. Several studies have shown that
depression is associated with poor adherence to self-care reg-
imens such as checking blood glucose, following a special diet
and medication compliance, as well as less sensitivity to insu-
lin effects on lowering blood glucose [6,10].
Two small randomized trials have shown that nortripty-
line [11] and fluoxetine [12] were more efficacious in con-
trolling depressive symptoms than placebo in patients with
major depression and diabetes. One cognitive behavioral
trial also demonstrated enhanced efficacy compared to an
educational diabetes group [13]. One of these 3 trials found
that improved depression outcomes was associated with
improved HbA 1 C levels [13]. These three trials enrolled a
combined total of less than 180 patients and lacked power to
study key outcomes such as the effect of enhanced treatment
of depression on self-care regimens (diet, exercise, refilling
medication), disability, quality of life, and medical costs.
Whether enhanced treatment of depression improves glyce-
mic control is also an unanswered question.
The study that we describe has two arms: 1) a popula-
tion-based epidemiologic investigation of the prevalence
Diabetes is a common and costly condition that affects 16
million Americans [1]. Patients with diabetes are at increased
risk of kidney disease, peripheral vascular disease, heart dis-
ease, lower extremity ulcers and amputations, retinal disease,
neuropathy, infections, digestive disease and periodontal dis-
ease [2]. The prevalence is as high as 20% in patients who are
65 years and over with significantly higher rates in minority
group members (African Americans, Hispanics and Native
Americans) [3]. The total direct medical costs and indirect
costs in the United States due to diabetes have been estimated
at $102 billion per year [4]. Patients with diabetes appear to
have increased risk of major depression. Depression may ad-
versely affect self-care regimens as well as increase risk of
complications such as diabetic retinopathy [5–7].
Anderson and colleagues’ recent meta-analysis of the
prevalence of major depression or depressive symptoms in
patients with diabetes found a two-fold higher prevalence
rate of depression in diabetics compared to controls in 20
controlled studies [5]. Current major depression was ob-
served in 10 to 15% of diabetics with similar prevalence
rates in Type 1 and Type 2 cases [5].
* Corresponding author. Tel.: 1-206-543-7177; fax: 1-206-221-
E-mail address: (W.J. Katon).
0163-8343/03/$ – see front matter © 2003 Elsevier Inc. All rights reserved.
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W.J. Katon et al. / General Hospital Psychiatry 25 (2003) 158 –168
and impact of depression in patients with diabetes enrolled
in a health maintenance organization; and 2) a randomized
controlled trial to test the effectiveness of collaborative care
interventions in improving the quality of care and outcomes
of depression among patients with diabetes in primary care.
This paper describes the design of these research studies and
the rationale for key methodologic decisions. The first part
of the Methods section will describe the recruitment for the
epidemiologic phase of the study, and the second part the
design of the randomized controlled trial.
2.2. Sample recruitment
A major methodologic issue was how to best screen and
enroll a representative sample of diabetic patients with ma-
jor depression and dysthymia. The screening was facilitated
by Group Health’s prior development of a population-based
diabetes registry. Patients are added to the diabetes registry
based on: 1) currently taking any diabetic agent; or 2) a
fasting glucose
also confirmed by a second test within one year; or 4) a
hospital discharge diagnosis of diabetes at any time during
GHC enrollment or two outpatient diagnoses of diabetes
[15]. The goal of the epidemiologic survey was to success-
fully screen at least 4,500 primary care patients with diabe-
tes with approximately 630 expected to meet criteria for
major depression and/or dysthymia. The goal of the ran-
domized trial was to enroll approximately 300 depressed
patients in the randomized controlled trial. After consider-
ing mail versus telephone screening for depression, we
decided on mail screening as the most cost effective mech-
anism based on prior studies by members of our study group
that were able to attain 60 to 65% recruitment rates with
mail screening [7,16]. To potentially increase patient re-
sponse rates, we presented the study to each of the 9 clinics
and requested written permission from all primary care
physicians to use a stamp of their signature in the approach
letter describing the study. Among the 113 doctors, 101
(90%) agreed to allow us to use their signature stamp. For
physicians refusing to let us use their signature, we used the
name of the GHC Chief of endocrinology, Dr. David Mc-
Patients were screened by mail in sequential waves with
approximately 700 questionnaires sent per month. A $3 gift
certificate for a local store was included with the mailing to
encourage response. If the patient did not return a mailed
packet by 4 weeks, a second packet was sent. If this second
packet was not returned by 2 weeks, the patient received a
telephone reminder call. The first mail-screen had a re-
sponse rate of approximately 38%, the second mailing in-
creased the response rate to 47%, and the combination of the
telephone reminder and a last mailing 6 months after the
telephone reminder increased the final response rate to
61.7%. Figure 1 describes the recruitment and reasons for
ineligibility or refusal at each phase of the study. The study
team has received permission from the Group Health Co-
operative Institutional Review Board to collect aggregate
data on nonrespondents to ascertain whether there are dif-
ferences in demographic (age, gender) or clinical variables
(health care costs, medical comorbidity, type of diabetes or
depression treatment, and HbA 1 C levels) between respon-
dents and nonrespondents.
A major methodological question was: “What is the best
depression screening tool to use?” Ideally this screen should be
brief, easy to score and provide both a DSM-IV diagnosis and
depression severity score. We elected to use the Patient Health
2. Methods
The Pathways Study was developed by a multidisci-
plinary team in the Department of Psychiatry at the Univer-
sity of Washington and the Center for Health Studies at
Group Health Cooperative. Group Health is a nonprofit
health maintenance organization with 30 primary care clin-
ics in Western Washington State.
The study was funded by the National Institute of Mental
Health Services (NIMH) Division of Intervention and Ser-
vices Research. The randomized controlled trial proposed to
test the effectiveness of a collaborative care intervention
versus usual care. Collaborative care is a multimodal inter-
vention that includes integration of a “care manager” (often
a nurse or mental health specialist) into primary care. The
“care manager” works with both the patient and primary
care physician and helps with developing a shared definition
of the problem, providing patient education and support,
developing a shared focus on specific problems, targeting
goals and a specific action plan, offering support and prob-
lem-solving to optimize self-management, achieving closer
monitoring of adherence and outcomes, and facilitating ap-
pointments to the primary care physician or specialist for
patients with adverse outcomes or side-effects [14]. The
study protocol was reviewed and approved by institutional
review boards at the University of Washington and Group
Health Cooperative.
2.1. Study setting
Nine Group Health Cooperative primary care clinics in
western Washington were selected for the study. We se-
lected clinics based on 3 criteria: 1) clinics with the largest
number of diabetic patients (to save screening and interven-
tion costs; 2) clinics within a 40-mile geographic radius of
Seattle in order to decrease travel time for nurse “care
managers”; and 3) clinics with the highest percentage of
minority patients. Because minorities have higher rates of
diabetes, we were able to enroll substantial numbers of
minority patients even though the general population was
predominantly Caucasian.
126 confirmed by a second out-of-range
test within one year; or 3) a random plasma glucose
W.J. Katon et al. / General Hospital Psychiatry 25 (2003) 158 –168
Fig. 1. Recruitment of epidemiologic study and randomized controlled trial.* Eligibility criteria: PHQ 10 or greater.** Patients were categorized as
“Ineligible – Other” if: 1) they were enrolled in another study; 2) their spouse was enrolled in PATHWAYS; 3) they were high risk for self-harm or if they
refused a self-harm assessment; or 4) there were other special circumstances (i.e., – there was one case where the team deemed someone ineligible due to
a recent hospitalization for drug overdose).
Questionnaire (PHQ) based on this questionnaire’s ability to
provide both a dichotomous diagnosis of major depression as
well as a continuous severity score [17]. The PHQ diagnosis of
major depression has been found to have high agreement with
the diagnosis of major depression based on structure psychi-
atric interview [17]. Because we were also interested in the
DSM-IV diagnosis of dysthymia, which is not included in the
PHQ, we added questions from the NIMH Diagnostic Inter-
view Schedule [18] on dysthymia.
2.3. Methodology of the Pathways randomized controlled
10 on the
initial PHQ in the mail screen, which has been found to be
the optimal cut-point in screening for major depression [17]
We required patients to have a second screen by telephone
about two weeks after scoring 10 or greater on the PHQ. On
this second screen, patients were required to have persistent
Patients were required to have a score of
W.J. Katon et al. / General Hospital Psychiatry 25 (2003) 158 –168
1.1. Double-screening eliminates those with tran-
sient or spontaneously resolving depression. A total of 348
patients were excluded based on an SCL
on the intervention developed for the IMPACT Study,
which randomized 1801 elderly primary care depressed
patients to a nurse collaborative intervention or usual care
[21]. A key design question for the team was: “Would this
intervention be designed to enhance treatment of depression
only, or to improve quality of care for both depression and
diabetes?” We elected to design an intervention to improve
quality of care and outcomes of depression but to not di-
rectly intervene to improve diabetes education or care, ex-
cept to the extent that addressing diabetes care issues arose
in the context of treating depression. An example of a
diabetes issue that could have been addressed in problem
solving therapy would be if the patient chose lack of exer-
cise or having problems with diet as a problem she or he
wanted to work on. By improving depression care, we could
then test effects of improved depression outcomes on dia-
betes self-care (diet, exercise, medication adherence), and
glycemic control.
Efficacy studies often ask questions such as “Is this
antidepressant more effective than placebo?” The health
services question for this effectiveness study was: “Is an
innovative method to improve service delivery that provides
guideline level antidepressant treatment or brief psychother-
apy more effective than usual care?” In developing this
intervention, we tried to optimize patient recruitment and
retention by providing an initial choice based on patient
preference of either antidepressant medication or problem
solving therapy (PST). It is controversial whether providing
patient choice of treatment leads to better outcomes, [22]
but choice is more like “real world” treatment decisions that
physicians and patients negotiate. We expected choice to
enhance recruitment and retention of patients. Choice of
treatment is also consistent with the Institute of Medicine’s
emphasis on understanding patients’ beliefs and preferences
in negotiating a treatment plan [23]. Problem solving ther-
apy was chosen because it is patient-centered, brief and
well-accepted by primary care patients due to its psycho-
educational content. Problem solving therapy has been
found to be as effective in randomized trials in primary care
as antidepressants in improving depressive symptoms of
patients with major depression [24]. It was also easier to
train Depression Care Specialists in providing PST than
other forms of psychotherapy.
To recruit a representative sample, we had few medical
or psychiatric exclusions. We elected to include diabetics
who were already receiving antidepressant medication or
psychotherapy from nonpsychiatrist clinicians, but who still
had high depression scores. This decision was based on
prior findings that showed that many primary care patients
with depression are exposed to antidepressants at lower than
guideline-recommended dosage and duration [20]. Eligible
patients were ambulatory, English-speaking, with adequate
hearing to complete a telephone interview, and planned to
continue to be enrolled in GHC over the next year. Psychi-
atric exclusions were: 1) currently in care by, or scheduled
to see, a psychiatrist; 2) a diagnosis based on Group
Health’s automated diagnostic data of bipolar disorder or
schizophrenia; 3) use of antipsychotic or mood stabilizer
medication based on Group Health’s automated pharmacy
in the prior year; and 4) mental confusion on the interview
suggesting significant dementia (Fig. 1).
2.4. Randomization
After completion of the baseline telephone interview and
verbal informed consent, participants were informed that
they would be randomly assigned to the Intervention or
Usual Care group through a computer generated number.
Patients were told that if they were assigned to the Inter-
vention group a nurse would call them within one week to
set up an appointment. If they were assigned to the Usual
Care group they would receive a mailed written informed
consent for telephone follow-up calls and HbA 1 C blood
draws to sign and mail back, and the first telephone survey
call in three months.
After the baseline telephone call, the research assistant
handed a face sheet with a study identification number to the
project coordinator to put in an Access data base. The
Access data base then automatically generated a random
assignment number which indicated whether patients were
in the Intervention or Usual Care group. Randomization
allocation occurred in blocks of eight. For those patients in
the intervention group, the computer generated a face sheet
with a patient name and phone number that the project
coordinator delivered to the nurses. For both Intervention
and Usual Care patients the computer then added the patient
identification data to the telephone survey data base with the
specific dates for the series of follow-up interviews.
2.6. What type of professional should be trained as a
Depression Care Specialist (DCS)?
Given the need for the DCS to be proficient in medica-
tion management and PST, to have experience working with
patients with one or more chronic medical illnesses, and to
be comfortable working in a primary care setting, we chose
registered nurses to implement collaborative care treatment.
Registered nurses at GHC were already providing disease
management for diabetes and congestive heart failure.
Therefore, this model would have a greater chance to be
2.5. Intervention design
The intervention was an individualized, stepped care
depression treatment program provided by a Depression
Clinical Specialist (DCS) nurse in collaboration with the
primary care physician. This intervention design was based
symptoms by having an SCL-20 depression [19] mean item
score of
W.J. Katon et al. / General Hospital Psychiatry 25 (2003) 158 –168
integrated into the GHC plans for improving disease man-
agement of depression after the study.
We also required a registered nurse (R.N.) degree, not a
nurse practitioner (ARNP), since primary care physicians
would continue to prescribe and this level of training is
more generalizable and cost-effective.
We hired three half-time registered nurses. They each
covered two to four primary care clinics, that were geo-
graphically as far as 25 miles apart, with case loads of 40 to
65 patients each once the study was fully underway.
nurse had supervision twice a month with a team of a
psychiatrist, psychologist (on PST) and family physician to
review new cases and patient progress. Nurses interacted
regularly (via written notes and verbally) with the primary
care physician treating the patient. On alternative weeks,
nurses reviewed cases by telephone with the psychiatrist
supervisor. The psychiatrist supervisor regularly reviewed
choices and dosages of medication and clinical response,
and recommended changes, which the nurse discussed with
the primary care physician and patient.
A unique clinical monitoring system was developed us-
ing Pendragon software [28] for a hand-held organizer for
the nurses to enter tracking data after each patient contact
including initial PHQ score, initial date of intake, last date
seen and last PHQ score, whether the patient has had a 50%
decrease in PHQ score by 12 weeks, initial treatment (PST
or antidepressants), current treatment and number of outpa-
tient and telephone contacts. This monitoring system al-
lowed nurses and supervisors to easily check which patients
were due for telephone or in-person follow-up visits. Each
week these data were transferred to an Access file and an
updated printout of all cases was used in weekly supervi-
sion. This facilitated each supervisor’s review of the process
and outcomes of care for the large number of cases being
The printout included an asterisk for cases that had not
decreased 50% or more on the PHQ at 10 weeks. Supervi-
sion started on new cases, progressed to asterisked cases and
then to cases in initial phases of treatment.
2.7. Training
Nurses received an initial one-week training course on
diagnosis and pharmacotherapy and an introduction to prob-
lem solving treatment methods. A psychiatrist, primary care
physician and psychologist participated in training. An in-
tervention manual from the IMPACT trial [25] was used to
train nurses on collaborative care, stepped care principles,
pharmacology and problem solving approaches.
Nurses were also trained using the manual for PST-PC
[26] during a training period following the protocol de-
scribed by Hegel and colleagues [27]. Formal training in-
cluded didactics, role play, observation of a videotaped
demonstration, and review of the treatment manual. Each
nurse was required to treat at least 4 depressed patients with
6 sessions of PST-PC over a 2-month period. Each session
was audiotaped, and sessions 1, 3 and 5 were rated using
Hegel’s PST Adherence and Competency Rating Scale [27].
Nurses were required to meet the criteria of at least 3 tapes
from each of two different patients’ audiotaped treatment
sessions being rated satisfactory by the team psychologist
(Dr. Ludman). During the training period, the nurses met
weekly with the psychologist for review of the audiotaped
sessions. During the course of the study, the nurses met
regularly with the psychologist to review audiotapes and
specific clinical problems arising in PST sessions. Group
supervision sessions were held weekly or twice a month for
the first months of the study, reducing in frequency over
time. During the second year, group supervision occurred
monthly. Individual PST-PC supervision sessions with
nurses occurred on an as-needed basis for review of difficult
2.9. Stepped care algorithm
50% decrease in severity based on the PHQ)
10 to12 weeks after Step 1 level treatment with either PST
or antidepressant medication, they could either: a) switch to
a second antidepressant with a different mechanism or side-
effect profile; b) switch to the alternative treatment (from
PST to medication or vice versa); or c) receive augmenta-
tion of PST or antidepressant medication with the first
treatment they had received. This change in treatment at 10
to 12 weeks was labeled Step 2 care. Another option in Step
2 was a psychiatric consultation to evaluate treatment op-
tions. For patients who received one or more Step 2 inter-
ventions, persistent symptoms (
2.8. Collaborative care
A team of clinicians delivered the treatment for interven-
tion patients. Nurses carried out the majority of treatment
that included an initial one hour visit followed by twice a
month, half-hour appointments (telephone and in-person) in
the acute phase of treatment (0 to 12 weeks). The first
appointment included a semistructured biopsychosocial his-
tory, patient education, development of the therapeutic al-
liance, understanding the patient explanatory model of ill-
ness and negotiation whether to start treatment with an
antidepressant medication or problem solving therapy. Each
50% improvement) and
lack of patient and clinician satisfaction with outcome after
a second treatment (8 to 12 weeks) could lead to referral to
the Group Health Cooperative (GHC) mental health system
for longer term follow-up including management by a psy-
chiatrist (Step 3).
A stepped care approach was used in which different
patients received different intensity of services based on
their observed outcome (Table 1). Stepped care recognizes
that patients have marked differences in psychiatric and
medical comorbidity as well as differences in response to
antidepressant medication and/or psychotherapy [29]. In the
Pathways trial if patients still had persistent depressive
symptoms (
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