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JAMA. Author manuscript; available in PMC 2010 June 14.
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JAMA. 2009 May 27; 301(20): 20992110. doi:10.1001/jama.2009.723.
Optimized Antidepressant Therapy and Pain Self-Management in

Primary Care Patients with Depression and Musculoskeletal
Pain: A Randomized Controlled Trial
Kurt Kroenke, MD, Matthew J. Bair, MD, MS, Teresa M. Damush, PhD, Jingwei Wu, MS,
Shawn Hoke, BA, Jason Sutherland, PhD, and Wanzhu Tu, PhD
Indiana University Divisions of General Internal Medicine and Geriatrics (Drs Kroenke, Bair, and
Damush) and Biostatistics (Dr. Tu and Mr. Wu), Indiana University School of Medicine,
Indianapolis, IN; VA HSRD Center of Excellence on Implementation of Evidence-Based
Practices, Roudebush VAMC, Indianapolis, IN (Drs. Bair and Damush and Mr Hoke); Regenstrief
Institute Inc, Indianapolis, IN (Drs Kroenke, Bair, and Damush, and Mr Hoke); and the Dartmouth
Institute for Health Policy and Clinical Practice, Hanover, NH (Dr. Sutherland)
Abstract
ContextPain and depression are the most common physical and psychological symptoms in
primary care, respectively. Moreover, they co-occur 30-50% of the time and have adverse
reciprocal effects on quality of life, disability, and health care costs.
ObjectivesTo determine if a combined pharmacological and behavioral intervention improves
both depression and pain in primary care patients with musculoskeletal pain and comorbid
depression.
Design, Setting, and PatientsRandomized controlled trial conducted at 6 community-based
clinics of 1 university primary care system and 5 general medicine clinics of 1 Department of
Veterans Affairs Medical Center. Recruitment occurred from January 2005 to June 2007 and
follow-up concluded in June 2008. The 250 patients had low back, hip or knee pain for 3
months and at least moderate depression severity (Patient Health Questionnaire-9 score 10).
InterventionPatients were randomly assigned to the intervention (n=123) or to usual care
(n=127). The intervention consisted of 12 weeks of optimized antidepressant therapy (step 1)
Corresponding author: Kurt Kroenke, MD, Regenstrief Institute, 6th Floor, 1050 Wishard Blvd, Indianapolis, IN 46202. Ph
317-630-7447 FAX 317-630-6611. kkroenke@regenstrief.org.
Trial Registration clinicaltrials.gov Identifier: NCT00118430
Author Contributions: Drs. Kroenke had full access to all of the data in the study and takes responsibility for the integrity of the data
and the accuracy of the data analysis.
Study concept and design: Kroenke, Bair, Damush, Sutherland
Acquisition of data: Kroenke, Bair, Damush, Hoke
Analysis and interpretation of data: Kroenke, Bair, Damush, Wu, Sutherland, Tu
Drafting of the manuscript: Kroenke, Wu, Hoke
Critical revision of the manuscript for important intellectual content: Kroenke, Bair, Damush, Wu, Sutherland, Tu
Statistical analysis: Kroenke, Wu, Sutherland, Tu.
Obtained funding: Kroenke.
Administrative, technical, or material support: Kroenke, Bair, Damush, Hoke.
Study supervision: Kroenke, Bair, Damush, Hoke
Financial Disclosures. Dr. Kroenke has received research funding from Eli Lilly, Pfizer, and Wyeth, and honoraria as a speaker,
consultant, or advisory board member from Eli Lilly, Pfizer, Wyeth, Astra-Zeneca and Forest Laboratories. Dr. Bair has received onetime consultant fees from Wyeth, Abbott, and Cephalon. No other authors reported disclosures.
Kroenke et al.
Page 2
followed by 6 sessions of a pain self-management (PSM) program over 12 weeks (step 2) and,
lastly, a continuation phase of therapy for 6 months (step 3).
Main Outcome MeasuresAssessments at baseline, 1, 3, 6, and 12 months for depression

(20-item Hopkins Symptom Checklist [HSCL-20]), pain severity and interference (Brief Pain
Inventory [BPI]) and global improvement in pain.
ResultsAt 12 months, 46 (37.4%) of the 123 intervention patients had a 50% or greater
reduction in depression severity from baseline compared with 21 (16.5%) of 127 usual care
patients (relative risk [RR], 2.3; 95% CI, 1.5 to 3.2), corresponding to a much lower number with
major depression (50 [40.7%] vs. 87 [68.5%]; RR, 0.6; 95% CI, 0.4-0.6). Also, a clinically
significant ( 30%) reduction in pain was much more likely in intervention patients (51 [41.5%]
vs. 22 [17.3%]; RR, 2.4; 95% CI, 1.6-3.2), as was global improvement in pain (58 [47.2%] vs. 16
[12.6%]; RR 3.7, 95% CI, 2.3-6.1). More intervention patients also experienced benefits in terms
of our primary outcome, which was a combined improvement in both depression and pain (32
[26.0%] vs. 10 [7.9%]; RR = 3.3; 95% CI, 1.8 to 5.4).
ConclusionOptimized antidepressant therapy followed by a pain self-management program
resulted in substantial improvement in depression as well as moderate reductions in pain severity
and disability.
Pain is the most common presenting somatic symptom in medical outpatients,1 and
depression is the most common mental disorder.2 Pain complaints account for more than
40% of all symptom-related outpatient visits3, and depression is present in 10-15% of all
patients attending primary care. Two-thirds of pain-related outpatient visits are due to
musculoskeletal pain, accounting for nearly 70 million outpatient visits in the US each year.3
Back and joint pain result in an estimated 200 million lost work days per year.4 Moreover,
pain and depression frequently coexist (30-50% co-occurrence) and have an additive effect
on adverse health outcomes and treatment responsiveness of one another.5
Two types of treatment one pharmacological and the other behavioral could prove
synergistic in the treatment of comorbid musculoskeletal pain and depression.
Antidepressants are a well-established therapy for depression, and there is also evidence for
at least moderate efficacy in pain which may vary by type of painful disorder and
antidepressant class.6,7 Pain self-management (PSM) programs have proven efficacious for
both low back pain and osteoarthritis (most commonly located in the hip and/or knee),8,9
with possible secondary benefits in reducing psychological distress.10-12 While literature
syntheses have suggested that self-management programs may have a smaller effect on
outcomes in musculoskeletal conditions than in other diseases such as diabetes, hypertension
and asthma13,14, others argue that outcomes such as pain and function are more complex as
are the components or PSM targeting painful conditions.15,16
The Stepped Care for Affective disorders and Musculoskeletal Pain (SCAMP) study was a
randomized clinical trial consisting of 12 weeks of optimized antidepressant therapy (step 1)
followed by 6 sessions of a pain self-management program delivered over 12 weeks (step 2)
and finally a 6-month continuation phase in which symptoms were monitored and treatments
reinforced. The study population comprised primary care patients with chronic
musculoskeletal pain and comorbid depression. The co-primary outcomes were depression
and pain severity at 12 months.
Kroenke et al.
Page 3
Methods
Study Sample
Details of the SCAMP trial design, study population, and measures have been previously
described.17 Patients were recruited from two primary care clinical systems in Indianapolis:
the Indiana University Medical Group Primary Care system (6 community-based clinical
sites were used) and the Richard L Roudebush Veterans Administration Medical Center 5
general medicine clinics. The local institutional review board approved the study and all
enrolled patients gave written informed consent.
Briefly, potential participants were primary care patients with comorbid musculoskeletal
pain and depression The pain had to be: (a) located in the low back, hip or knee; (b)
persistent for 3 months or longer despite conventional analgesic treatment, defined as prior
use of at least two different analgesics; (c) at least moderate in severity, defined as a Brief
Pain Inventory score of 5 or greater.18,19 The depression had to be of at least moderate
severity, i.e., a PHQ-9 score 10 and endorsement of depressed mood and/or anhedonia.
More than 90% of patients fulfilling this PHQ-9 criterion have major depression and/or
dysthymia, and the remaining patients have clinically significant depression with substantial
functional impairment.20,21 Patients on antidepressants who still met the entry criterion for
clinical depression were eligible if they had been on an adequate dose of the antidepressant
for at least 12 weeks.22,23. Excluded were individuals with severe cognitive impairment,
bipolar disorder, substance use disorder, schizophrenia, a pain-related disability claim
currently under adjudication, plans to become pregnant in the next year, a life expectancy
less than 12 months, or inability to speak English. This trial was approved by the Indiana
University Institutional Review Board and was monitored by a local independent Data
Safety Monitoring Committee.
Figure 1 outlines the participant enrollment and follow-up in SCAMP. Of 2050 patients
screened, 1294 were not eligible, most often because they were either not depressed (n =
500) or had pain that was minimal, of short duration, or did not require analgesics (n = 137).
Of the 756 eligible patients, 250 (33%) enrolled in the trial by providing informed consent
and completing a baseline interview after which they were randomized to one of the two
study groups.
Randomization and Blinding
Participants were randomized to intervention vs. usual care groups with randomization
stratified by pain location (back vs. leg) and clinic site (university vs. VA). Randomization
lists were computer-generated and treatment assignments were supplied in sealed opaque
envelopes. The nurse care manager consented individuals and revealed the randomization
assignment for each participant by opening the next envelope in the sequence after
completion of baseline assessment. All baseline and follow-up outcome assessments were
conducted by a research assistant blinded to treatment allocation and uninvolved in care
management of participants.
Outcome Assessment
Depression diagnoses were established with the PRIME-MD, which categorizes individuals
into 3 DSM-IV diagnostic subgroups: major depression, dysthymia, and other depression.24
Depression severity was assessed, as a primary outcome, with the 20-item Hopkins
Symptom Checklist (HSCL-20) which has established sensitivity to change25 and is widely
used in effectiveness trials of depression in primary care.21-23,26,27 Pain outcomes included
core domains recommended by IMMPACT guidelines for chronic pain clinical trials.28 The
Brief Pain Inventory (BPI) was the primary pain outcome.29 The BPI includes a 4-item
Kroenke et al.
Page 4
severity scale (current pain and worst, least, and average pain in past week) and a 7-item
interference scale (the degree to which pain interferes with general activity, mood, walking,
work, sleep, relations with other people, and enjoyment of life. Global change in pain was
assessed with a 7-point scale with the options being worse, the same, or a little, somewhat,
moderately, a lot, or completely better. Secondary measures of pain included the Graded
Chronic Pain Scale (GCPS) and Roland Disability Scale. In addition to its pain severity and
pain disability scales, the GCPS also asks how many days in the past 3 months usual
activities have been limited by pain.30 The Roland Disability Scale is a 24-item pain-specific
measure of physical disability validated in patients with back pain31 and chronic noncancer
pain.32
Several scales or items from the SF-36 33,34 assessed social functioning, vitality, bodily
pain, and a single general health perceptions item that has shown to predict long-term health
outcomes.35 Anxiety was assessed by the GAD-7, a screening and severity measure
validated for the four most common anxiety disorders: generalized anxiety, panic, social
anxiety, and posttraumatic stress disorder.36,37 Because pain treatment and pain outcomes
may vary by race or ethnicity,38 race/ethnicity (identified by the patient from preselected
options) was also included as a demographic characteristic.
Medication refill (i.e., antidepressants and analgesics) and health care use data was extracted
from electronic medical records for all participants for the 12-month study period following
their enrollment interview. The one exception was that antidepressant use in the intervention
group was extracted from care manager logs since intervention participants were provided
antidepressants by the study rather than through a prescription. Most patients receive all or
most of their medications from the pharmacies inputting prescription information into these
EMRs. To assess additional co-interventions, a treatment survey asked participants about
any treatments they received for pain and depression during the preceding 3 months at
baseline and at the 3, 6, and 12-month follow-up interviews.
Intervention
The intervention model in SCAMP is based upon a depression care management team
consisting of a nurse care manager (NCM) supervised by a physician depression specialist
and proven effective in multiple primary care depression trials.39 The first 3 months
consisted of optimized antidepressant therapy actively managed by the NCM (step1),
followed by six sessions of a pain self-management program delivered every other week
during the second 3 months (step 2). The final 6 months of the study was a continuation
phase focused on relapse prevention. The protocol called for 5 in-person contacts (baseline,
6, 12, 16, and 20 weeks) and 8 telephone contacts (1, 3, 9, 14, 18 and 22 weeks; 8 and 10
months). Extra contacts could occur depending upon treatment changes or patient's clinical
needs.
Step 1: Optimized Antidepressant Therapy (Weeks 1-12)For intervention
patients already on an antidepressant at baseline, dose adjustments or medication changes
were considered since, despite antidepressant therapy, the patients remain clinically
depressed. For patients not on an antidepressant or requiring antidepressant changes, the
Appendix outlines the antidepressant algorithm for SCAMP, the rationale for which has
been previously described.17 Since there is no evidence that one antidepressant is superior to
another in terms of efficacy.40,41, SCAMP was not designed to test any particular
antidepressant but, instead, optimal medication management that is both effective and
tolerated in an individual patient. An SNRI was offered first in the algorithm because of
evidence suggesting that norepinephrine reuptake inhibition (which occurs to a greater
degree with tricyclic or SNRI than with SSRI antidepressants) may be particularly important
Kroenke et al.
Page 5
in descending inhibitory pathways related to pain.7 Venlafaxine was selected for SCAMP
because it was the most commonly used SNRI at the beginning of the trial and was also
scheduled to become generic by the time of study completion.
Clinical response was assessed at 3 weeks and, if there was not a clinically meaningful
response defined as a 5 point drop in the PHQ-925 -- a dose increase occurred. Participants
who failed to achieve a PHQ-9 <10 and a 50% reduction in PHQ-9 score at 6 weeks were
switched to a different antidepressant. Of note, depression rather than pain response dictated
antidepressant adjustments. The target PHQ-9 was a score < 5 which approximates
depression remission.42
Patients randomized to usual care were informed they had depressive symptoms and that
they should seek advice about treatment. There were no other attempts by study personnel to
influence depression or pain management unless a psychiatric emergency (e.g., suicidal
ideation) arose.
Step 2: Pain Self-Management (PSM) Program (Weeks 13-26)The PSM sessions

were modeled after the successful Stanford self-management program8,9,43 and based on
social-cognitive theory44 focusing on increasing self-efficacy and social support to selfmanage low back pain or arthritis symptoms. Participants learn to modify their behavior
through use and discussion of behavioral plans and problem-solving techniques to sustain
behavioral change. The nurse care manager conducted the PSM sessions using a
standardized, written protocol adapted from our previous work with musculoskeletal pain.
45,46 Details of the PSM program including care manager training and procedures to assure
fidelity are detailed elsewhere.17 Briefly, patients learn about chronic pain including triggers
and flare-ups; coping with fear and other negative emotions; and strategies for physical
activity, muscle relaxation, deep breathing, distraction, sleep hygiene, and working with
providers and employers. Each session, the nurse care manager introduces new strategies for
patient self-management, assists the patient in choosing strategies, and supervises the patient
as he/she practices the chosen strategy. To promote perceived self-efficacy, patients receive
individualized feedback about their progress.
Step 3: Continuation Phase (Weeks 27-52)Intervention patients received scheduled

nurse care manager calls at 8 and 10 months to assess symptoms and to evaluate
antidepressant and PSM adherence. The care manager assessed current self-management
strategies and assisted patients with new behavioral plans. Subjects with a PHQ-9 score 5
could have their antidepressant dose increased or be switched to a different antidepressant if
they had not yet had trials of 2 different antidepressants. Those failing 2 different
antidepressant trials were offered a referral to psychiatry. Only those refusing referral to
psychiatry could have trials of several more antidepressants during the 12-month study. If
antidepressant changes did occur, additional nurse care manager calls were scheduled as in
Step 1.
Analysis
Analyses were based on intention-to-treat in all randomized participants. Our primary
outcome was a composite depression-pain response at 12 months defined as both a 50%
improvement in depression and 30% improvement in pain, the standard thresholds for
moderate improvement in depression and pain clinical trials.47,48 This composite outcome
used the HSCL-20 and BPI total scores; the latter was the average of the 4 BPI severity and
the 7 BPI interference items, since both dimensions are considered essential in assessing
outcomes of chronic pain therapy.28 The internal reliabilities of the BPI total, severity, and
interference scores were similar in our sample (Cronbach's alpha = 0.89, 0.88, and 0.83,
Kroenke et al.
Page 6
respectively). With 97 subjects per group, we projected 80% power to detect a 20% absolute
difference in response rates with two-tailed < .05. Enrolling 250 subjects allowed up to a
25% attrition rate. The resulting sample size also provided 80% power to detect a moderate
treatment effect size of 0.4 SD on depression or pain as individual outcomes. While our prespecified analysis was to compare groups primarily at 12 months and secondarily at
intermediate time points, we also conducted repeated measures analyses on the primary
depression (HSCL-20) and pain (BPI) outcomes using mixed-effects regression models.
Analyses were not adjusted for multiple comparisons. This does not affect interpretation of
our primary outcomes, but findings for secondary outcomes should be interpreted cautiously
unless they are highly significant (P < .001). Analyses were performed using SAS Version
9.1 (SAS Institute, Cary, North Carolina).
Baseline characteristics were reported and comparisons were made between the two
treatment groups. Categorical data were reported as frequencies (%); and differences
between groups were compared with chi-square tests. Continuous data were reported as the
mean and standard deviation (SD), and the difference between groups were tested using
two-sample t-tests.
There was no difference in the magnitude of missing data between the treatment groups.
Further, logistic regression models showed that intervention and control participants for
which 12-month data was missing did not differ in terms of age, gender, pain location, clinic
site, depression or pain severity. Missing outcomes during the follow-up period were
imputed using the last-observation-carried-forward (LOCF) method. To assess the
robustness of the analytical results under alternative imputation methods, we repeated
analyses on all outcomes using multiple regression imputation as well as available data only
(no imputation). Results did not differ between these 2 methods and LOCF; thus, we report
the results from LOCF because it is the most conservative imputation strategy and also
allows straightforward imputation of categorical as well as continuous variables.
Using the 1, 3, 6, and 12-month follow-up data, between-group differences were reported as
mean (95% CI) differences for continuous variables and relative risks (95% CI) for
categorical variables.49 For key pain and depression continuous outcomes, standardized
effect sizes were calculated as the mean group difference divided by the pooled standard
deviation for the measure at baseline. For key binary outcomes, the number needed to treat
(NNT) was calculated as the reciprocal of the difference in the response rates.50
Results
Baseline Characteristics of Study Sample
As shown in Table 1, there were no significant baseline differences between the intervention
and usual care groups. Overall, the mean age of the 250 participants was 55.5 years; 52.8%
were women; 60.4% were white, 36.4% black, and 3.2% other. Work status was 25.6%
employed, 31.6% unemployed or unable to work, and 42.8% retired. The site of pain was
the back in 60.4% of subjects and the hip or knee in 39.6%.
As shown in Table 2, intervention and usual care patients were also similar in terms of
baseline depression and pain measures. In terms of depression diagnoses, 74.8% of the
sample met DSM-IV criteria for major depression, 20.8% for dysthymia only, and 4.4% for
minor depression. The mean HSCL-20 score of 1.89 (on a 0-4 scale) represents moderately
severe depressive symptoms. Likewise, the mean BPI severity and interference scores of
6.15 and 6.97 (on a 0-10 scale) respectively represent moderately severe pain. This level of
disability is confirmed by a Roland disability score of 17.4 (on a 0-24 scale, where a higher
Kroenke et al.
Page 7
score indicates greater pain-related disability) and an SF-36 bodily pain score of 26.8 (on a 0
to 100 scale, where 0 represents the worst pain-related impairment).
Clinical Outcomes
As shown in Table 2, the intervention group had significantly better HSCL-20 depression
outcomes; the difference between groups at baseline and 12 months was -0.11 and -0.55,
respectively. Accounting for baseline differences, this resulted in a net between-group
difference of - 0.44 (95% CI, -0.62 to -0.26). This equates to a standardized treatment effect
size of 0.67 (0.44 divided by the pooled SD for the HSCL-20 at baseline of 0.653). Figure 2
illustrates the substantial intervention effect that occurred by 1 month and was sustained
over the 12-month trial. The intervention group also was much more likely to experience
depression response (46 [37.4%] of the 123 intervention patients vs. 21 [16.5%] of the 127
patients; RR = 2.3, 95% CI, 1.5-3.2) and complete remission (22 [17.9%] vs. 6 [4.7%]; RR =
3.8, 95% CI, 1.6-7.6) at 12 months, corresponding to a much lower number with major
depression (50 [40.7%] vs. 87 [68.5%]; RR = 0.6, 95% CI, 0.4-0.8). The number needed to
treat (NNT) for depression response was 1/(.374 - .165), or 4.8 (95% CI, 3.4-8.3)
Table 2 also shows the effectiveness of the intervention on pain outcomes. The intervention
group had significantly better BPI severity (net between-group difference of -0.98; 95% CI,
-1.48 to -0.47) and BPI interference (net between-group difference of -1.27; 95% CI, -1.88
to -0.66) scores at 12 months. This represented standardized effect sizes of 0.54 for BPI
severity and 0.62 for BPI interference. Figure 3 illustrates the significant intervention effect
on BPI interference (Figure 3A) and BPI severity (Figure 3B) occurring by 1 month and
sustained over the 12-month trial. Though both dimensions of pain improved significantly,
the reductions in pain interference were even greater than in pain severity The intervention
group was also much more likely to experience a 30% reduction in pain at 12 months (51
[41.5%] vs. 22 [17.3%]; RR = 2.4, 95% CI, 1.6-3.2). This corresponds to a NNT of 4.1 (95%
CI, 3.0-6.5)
In terms of our trial's primary and most conservative outcome, the intervention group was
significantly more likely to experience a composite response, defined a priori as a 50%
reduction in depression and a 30% reduction in pain. This difference in composite
response rates was significant at both 6 months (23.6% vs. 7.9%; RR = 3.0, 95% CI, 1.6-5.1)
and 12 months (32 [26.0%] vs. 10 [7.9%]; RR = 3.3, 95% CI, 1.8-5.4). This corresponds to a
NNT of 5.5 (95% CI, 3.7-10.9). Finally, the statistical significance of the intervention effect
was similar when fitting mixed effects regression models for our repeatedly measured
primary outcomes, i.e., HSCL-20 depression score, BPI severity, and BPI interference.
Intervention patients were much more likely than those in usual care to report overall
improvement in their pain at 6 months (61 [49.6%] vs. 19 [15.0%]; RR, 3.3; 95% CI,
2.2-5.2) which was sustained at 12 months (58 [47.2%] vs. 16 [12.6%; RR, 3.7; 95% CI,
2.3-6.1]. Correspondingly, there were fewer patients in the intervention group who were
worse (15 vs. 44) and unchanged (50 vs. 67) at 12 months. Of the 58 intervention
participants whose pain was better at 12 months, 8 were a little better, 21 were somewhat or
moderately better, and 29 were a lot or completely better. In contrast, only 16 usual care
participants reported improved pain at 12 months, of whom 3 were a little better, 6 were
somewhat or moderately better, and 7 were a lot or completely better.
Table 3 compares the groups in terms of other pain and quality of life outcomes. The
intervention group had better outcomes in terms of secondary pain measures (i.e., Roland
pain disability, GCPS pain scores, and SF-36 bodily pain), less severe anxiety (GAD-7), and
better health-related quality life (SF-36 vitality and general health perception scores).
Kroenke et al.
Page 8
Care Manager Contacts and Antidepressants Used in the Intervention Group
The intervention protocol called for 5 in-person care manager contacts and 8 telephone
contacts over 12 months, with extra contacts allowed depending upon treatment changes or
patient's clinical needs. The mean (SD) number of in-person contacts that actually occurred
was 2.5 (1.3), and the mean (SD) number of telephone contacts was 11.5 (5.1). Thus, the
average intervention patient had 14 contacts over the 12-month study, 82% of which were
by phone. The variability was due to early dropout by some intervention patients, extra
contacts required for others, and substitution of telephone contacts when an in-person
contact was not feasible for the patient.
The antidepressant initiated or continued at baseline was venlafaxine in 75 (61%) of the

intervention patients, an SSRI in 39 (32%), or another antidepressant including
combinations in 9 (7%). At 12 months, there were 26 (21%) intervention patients on
venlafaxine, 36 (29%) on an SSRI, 22 (18%) on other antidepressants including
combinations, 16 (13%) on no antidepressant, and 23 (19%) for which the information was
not known. Of the 100 intervention subjects whose antidepressant status was known at 12
months, 41% had continued their initial antidepressant, 43% had switched to a different
antidepressant (n = 38) or combination pharmacotherapy (n = 5), and 16% were on no
antidepressant. Thus, we know that, at a minimum, 43 (35%) of the 123 patients in the
intervention group had an antidepressant switched or added during the study. The mean dose
for the 79 patients known to be on antidepressant monotherapy at 12 months was 147 mg for
venlafaxine (n = 26), 140 mg for sertraline (n = 24), 295 mg for buproprion (n = 10), 36 mg
for mirtazapine (n = 7), 27 mg for fluoxetine (n = 6), 40 mg for citalopram (n = 4), and 15
mg for paroxetine (n = 2).
12-Month Medication and Health Care Use
Table 4 summarizes the antidepressant and analgesic refill information as well as health care
use for all intervention and usual care participants during the 12 month study period
following their enrollment interview. All data was derived from the electronic medical
records, except antidepressant use in the intervention participants since they were provided
antidepressants free of charge as part of the study. Compared to the usual care, those in the
intervention group were on antidepressants during the 12-month study for a much longer
period of time (9.3 vs. 2.0 months, P < .0001). Notably, 83 of the participants in the
intervention group were on antidepressants all 12 months of the study compared to only 5 in
the usual care group (67.5% vs. 3.9%). Of the 52 usual care participants for whom there was
EMR data showing any antidepressant use, only 9 (17%) had EMR evidence of an
antidepressant being switched or added during their 12 months in the study. There were no
significant group differences in terms of low-dose tricyclic, opioid, or non-opioid analgesic
use.
Intervention participants had slightly more mental health visits, emergency department visits
and hospital days and slightly fewer medical specialty visits. Removing extreme outliers
from the analyses did not change the results. Although statistically significant, the absolute
magnitude of these differences was small.
Patient-Reported Co-Interventions
Participants were asked to report treatments received for pain or depression since their last
interview at 3 timepoints: 3, 6, and 12 months. Patients were classified as having each type
of treatment either not at all or at least once during the 12-month period. Intervention
patients were slightly less likely than usual care patients to report changes in their pain
medicine (52% vs. 63%, P =.016) but did not differ significantly in their likelihood of
visiting a pain clinic (34% vs. 28%) or having pain-related emergency department visits
Kroenke et al.
Page 9
(22% vs. 30%), hospitalizations (10% vs. 8%), X-rays (41% vs. 49%), or laboratory tests
(20% vs. 31%, P = .06). There were also no differences in visits to a psychiatrist,
psychologist or counselor (11% vs. 13%) or to specialists for pain such as physical
therapists, orthopedists, rheumatologists, neurologists, or complementary medicine
providers. Intervention and usual care participants were also equally likely (50% vs. 49%) to
report a change in their medication for mood, nerves or depression.
Discussion
The SCAMP trial has several important findings. First, optimized antidepressant therapy
coupled with a pain self-management program produced substantial reductions in depression
severity as well as enhanced response and remission rates. Second, the intervention also
resulted in moderate reductions in both pain severity and pain-related disability. Third, the
benefits on both depression and pain outcomes were sustained over the 12 months of the
trial, including the 6-month continuation phase.
The effect size of the SCAMP intervention on depression outcomes was similar to that seen
in patient populations without chronic pain. In a systematic review of 28 randomized
controlled trials of multi-component interventions for primary care patients receiving acutephase treatment for depression, Williams et al found an 18.4% median absolute increase in
patients with a 50% improvement in symptoms (range, 8.346%) and a median absolute
increase of 16.7% (range, 10.640%) in remission from depression.39 The median absolute
increases in SCAMP were 20.9% for a 50% response (i.e., 37.4% response in the
intervention group vs. 16.5% in the usual care group) and 13.2% for remission (17.9% vs.
4.7%). Also, the number needed to treat (NNT) of 4.8 to achieve a treatment response for
depression is similar to the NNT of 4 in a Cochrane review of antidepressants compared
with placebo or no treatment in medically ill adults.51
Some of the reasons for improved depression outcomes in SCAMP may be that intervention
patients were on antidepressants more months than usual care patients (9.3 vs. 2.0 months),
were more likely to be on an antidepressant all 12 months of the study (67.5% vs. 3.9%),
and more likely to have an antidepressant switched or added during the study (35% vs.
17%). Continuing an antidepressant at least 6-12 months is known to enhance depression
outcomes, and STAR*D and other trials have taught us that an inadequate response to the
initial antidepressant is not uncommon and may require a change in medication.39,52 The
assessment of antidepressant use may have been more accurate in intervention patients
whose medication was provided by the nurse care manager and documented in the study
logs, while antidepressant use in usual care patients depended entirely on refill information
in the electronic medical record. However, it is unlikely that group differences as large as we
found for antidepressant usage are entirely due to ascertainment bias.
The effect size of the SCAMP intervention on pain outcomes 0.54 for pain severity and
0.62 for pain interference was notable. Chronic pain is difficult to treat and a 30% reduction
is typically judged a clinical response as determined by patient-rated quality of life and
perceptions of analgesic efficacy53 in contrast to the 50% reduction required for
depression. Using this threshold, a clinical response in pain was much more likely in the
intervention compared to the control group (41.5% vs. 17.3%, or a NNT of 4.1).
Impressively, when rating overall change in pain, 47.2% of intervention patients reported
improvement at 12 months, compared to only 12.6% of control patients. Thus, the SCAMP
intervention showed benefits in terms of 3 pain outcomes considered relevant in clinical
trials: pain severity, pain interference, and global pain improvement. It is possible that pain
improvement in our trial reflected a main effect of improved mood (i.e., an antidepressant
effect on mood rather than an analgesic effect), and that as depression lifts, patients may
Kroenke et al.
Page 10
experience pain as being less intense and less disabling. Conversely, it is also possible that
the improvement in depression was mediated by an improvement in pain (i.e., as pain
improves, patients feel less depressed) or that both depression and pain lessened as a result
of treatment effects on a common pathway.
The largest reductions in depression and pain were seen early (i.e., during the first month of
optimized antidepressant therapy) and were sustained during the remainder of the trial.
Thus, the added value of the pain self-management program cannot be ascertained in
SCAMP. We had postulated that improvements in pain that might occur with optimized
antidepressant therapy would be further enhanced with a behavioral intervention designed to
improve pain coping and other self-management skills. It is possible that, without the pain
self-management program, patients whose pain initially improved might have suffered a
relapse. However, it is also possible that antidepressant continuation, as occurred in
SCAMP, is sufficient. To test whether pain self-management provides any benefits beyond
optimized antidepressant therapy would require a parallel group or factorial trial design
rather than the sequential approach used in the current study.
While the between-group differences (i.e., treatment effect) were similar to previous
depression trials, the absolute response and remission rates in both intervention and control
groups were low compared to other depression care management studies.39,54 and closer to
that seen in populations with more medical comorbidity.22,51 Indeed, secondary analyses of
two collaborative care interventions found that high baseline pain reduces depression
improvement rates.55,56 A secondary analysis of patients with comorbid pain in a geriatric
depression trial57 found a much more modest ES for pain outcomes than for depression.
Thus, additional interventions to co-manage pain (e.g., optimized analgesic management)
may be necessary to further improve response and remission rates. For example, Dobscha
and colleagues recently found that a collaborative care intervention for chronic pain that
included clinician education, patient education and activation, symptom monitoring,
feedback and recommendations to clinicians, and facilitation of specialty care produced
modest improvement in both pain and depression outcomes.58
In addition to improving depression and pain outcomes, the SCAMP intervention also
demonstrated benefits in terms of secondary measures such as anxiety, functional
impairment, and quality of life. There was also a nonsignificant trend towards fewer painrelated disability days. Since pain and depression are among the two leading causes of
decreased work productivity59,60, interventions that improve both of these symptoms as well
as their adverse impact on functional status might be particularly desirable from not only the
patient but also the employer and societal perspectives.
SCAMP used an antidepressant algorithm rather than a single antidepressant, and more than
half of the patients discontinued or switched from their initial antidepressant by 12 months.
Therefore, the superiority of one antidepressant over another in comorbid depression and
pain cannot be determined. Studies to date have failed to establish differential efficacy
among antidepressants in terms of depression outcomes.21,52 For pain, tricyclic
antidepressants (TCAs) may be somewhat more effective than SSRI antidepressants.6,61,62
However, head-to-head comparisons are few, previous trials are short in duration, and many
trials have used lower doses of TCAs than are normally required for an optimal effect on
depression. Several SNRI antidepressants now have FDA indications for treating
neuropathic pain and fibromyalgia7 but their efficacy in the painful conditions studied in our
SCAMP trial (low back pain and osteoarthritis of the hip and knee) requires further research.
Also their relative superiority compared to other antidepressants in terms of improving pain
is less certain63 and would require active comparator trials. Notably, all antidepressants used
in our SCAMP trial are now available in generic formulations.
Kroenke et al.
Page 11
Neither data from electronic medical records nor patient self-report suggested that group
differences were significantly confounded by co-interventions. The average intervention
patient averaged slightly more than one care manager contact per month over the 12-month
study, with most of these (82%) occurring by telephone. Health care use was slightly higher
for intervention patients in a few categories of visits, but these differences did not appear
clinically significant. Though we did not design our single-site study to conduct a formal
cost-effectiveness analysis, the care manager contacts together with greater antidepressant
use and no decrease in health care use certainly indicates there was some added cost to
achieve the improved depression and pain outcomes in the intervention group. This is
consistent with many other primary care trials comparing enhanced depression care to usual
care,64,65. However, a recent multi-center trial with sophisticated cost analyses found that
the cost per quality-adjusted life year for enhanced depression care compared favorably with
many other medical interventions66 and it is possible that increased costs incurred during the
first year may be recouped with cost savings in subsequent years.67
Our study has several limitations. First, since patients were enrolled from urban underserved
and veteran clinics, the generalizability of our results to other primary care populations
needs to be demonstrated. However, adverse socioeconomic factors more prevalent in our
sample tend to make treatment of depression and pain more difficult, so the substantial
effects we observed are noteworthy. Second, since only one-third of eligible patients agreed
to enroll, the extent to which the benefits we found are generalizable to patients not desiring
participation in a trial is uncertain. Third, SCAMP is a multi-component effectiveness trial.
Therefore, to what degree benefits can be specifically attributed to the antidepressantbehavioral intervention vs. the nonspecific effects of care manager contacts cannot be
precisely determined. Also, the lack of blinding in an effectiveness design may inflate
somewhat the benefits specifically attributable to the intervention. However, a recent
literature synthesis of depression care management trials showed that, like our SCAMP
study, an effectiveness trial with a usual care control group has been the most common study
design.39 Also, a number of patients in the usual care group received antidepressants which
might tend to reduce the effect size of the intervention. Importantly, the two treatment
groups did not differ in terms of self-reported pain or depression co-interventions over the
12-month trial.
In summary, SCAMP showed that optimized antidepressant therapy coupled with pain selfmanagement in patients with comorbid pain and depression can produce substantial
improvements in both depression and pain. At the same time, additional interventions may
be needed to produce larger improvements in pain and higher depression response and
remission rates. Strategies might include optimized analgesic management, cognitivebehavioral therapy6,68, or augmentation strategies.41 While numerous trials have shown that
enhanced care for depression is equally or more cost-effective than the treatment of chronic
medical diseases, the lack of parity for mental disorders leads some payers to insist that
depression care must be cost-neutral or even cost-savings.64,65 A recent trial demonstrated
that depression care management improved workplace as well as clinical outcomes.69 Since
pain and depression are among the leading causes of decreased work productivity, an
intervention that is effective for both conditions may further strengthen the business case.
Also, an intervention that allows a care manager to cover several conditions rather than a
single disorder may enhance its implementation and cost-effectiveness. Given the
prevalence, morbidity, disability, and costs of the pain-depression dyad, the SCAMP results
have important implications.
Kroenke et al.
Page 12
Acknowledgments
The authors gratefully acknowledgement the care management provided by Carol Kempf and Gloria Nicholas and
the research assistance provided by Monica Huffman.
Funding/Support: This work was supported by grant R01 MH-071268 from the National Institute of Mental
Health, National Institutes of Health. Dr. Kroenke was the principal investigator.
Role of the Sponsor: The sponsor provided financial support for the study only and had no role in the design and
conduct of the study; the collection, management, analysis, and interpretation of the study; or in the preparation,
review, or approval of the manuscript.
Funding: This study was supported by a grant from the National Institute of Mental Health to Dr. Kroenke
(MH-071268)
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Figure 1.
Flowchart of participants in the SCAMP trial
Kroenke et al.
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Figure 2.
Mean HSCL-20 depression scores in the intervention (solid line) and usual care (dashed
line) groups. HSCL-20 scores can range from 0 to 4. Error bars indicate SEs. All study
participants are included in each time period since last-observation carried forward
imputation is used.

Kroenke et al.
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Figure 3.
Mean BPI pain interference (3A) and pain severity (3B) scores in the intervention (solid
line) and usual care (dashed line) groups. BPI scores can range from 0 to 10. Error bars
indicate SEs. All study participants are included in each time period since last-observation
carried forward imputation is used.

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Table 1
Baseline Characteristics of the 250 Participants in the SCAMP Trial
Baseline Patient Characteristic

Mean (SD) age, yr
Women, n (%)
Intervention Group (N=123)
Usual Care Group (N=127)
P Value
55.2 (12.6)
55.8 (11.1)
.70
69 (56)
63 (50)
.30
Race, n (%)
.29
White
75 (61)
76 (60)
Black
42 (34)
49 (39)
Other
6 (5)
2 (2)
Education, n (%)
.65
Less than High school
28 (23)
32 (25)
High school
54 (44)
48 (38)
At least some college or trade school
41 (33)
46 (37)
48 (39)
44 (35)
Employed
36 (29)
28 (22)
Unemployed or unable to work
39 (32)
40 (32)
Retired
48 (39)
59 (47)
Back
76 (62)
75 (59)
Hip or knee
47 (38)
52 (41)
Married, n (%)
Employment status, n (%)
.47
.35
Pain location, n (%)
.66
Clinical site, n (%)
.96
Veteran administration (VA)
50 (41)
52 (41)
University clinics
73 (59)
75 (59)
Median duration of pain, yr (interquartile range) *
8 (3-21)
10 (4-20)
.81
Mean (SD) no. of medical diseases
2.7 (1.6)
2.7 (1.4)
.62
Opioid analgesics
63 (52)
49 (42)
.12
Non-opioid analgesics
88 (72)
85 (72)
.99
Tricyclic (TCA) antidepressants
29 (24)
16 (14)
.04
Non-TCA antidepressants
Baseline medications, n (%)
28 (23)
17 (14)
.09
Nonpharmacological treatments for pain
31 (25)
28 (22)
.56
Have seen mental health specialist
51 (41)
59 (46)
.43
Middle 50% range of values, i.e., difference between 1st and 3rd quartiles (25th-75th percentiles)
Baseline medication data was available for 122 (99%) of stepped care and 118 (93%) of usual care subjects. These numbers were used as the
denominators for calculating the proportion of patients on various medications.
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Table 2
Primary Depression and Pain Outcomes (Last-Observation Carried Forward)
Clinical Outcome
Intervention (123)
Usual Care (127)
Between-Group Difference or
Relative Risk (95% CI)
P value
Baseline
1.83 (0.66)
1.94 (0.65)
-0.11 (-0.27 to 0.06)
.20
6-Month follow-up
1.16 (0.77)
1.64 (0.70)
-0.47 (-0.66 to -0.29)
<.0001
12-Month follow-up
1.14 (0.69)
1.69 (0.74)
-0.55 (-0.73 to -0.37)
<.0001
Baseline
90 (73.2)
97 (76.4)
0.9 (0.8 to 1.1)
.56
12-Month follow-up
50 (40.7)
87 (68.5)
0.6 (0.4 to 0.8)
<.0001
6-Month follow-up
47 (38.2)
18 (14.2)
2.7 (1.8 to 3.8)
<.0001
12-Month follow-up
46 (37.4)
21 (16.5)
2.3 (1.5 to 3.2)
.0002
Baseline
6.16 (1.76)
6.14 (1.78)
0.02 (-0.42 to 0.46)
6-Month follow-up
5.24 (2.51)
5.86 (2.20)
-0.63 (-1.22 to -0.04)
.0361
12-Month follow-up
5.08 (2.54)
6.03 (2.08)
-0.95 (-1.53 to -0.38)
.0014
Baseline
6.84 (2.15)
7.09 (1.97)
-0.25 (-0.76 to 0.26)
.34
6-Month follow-up
5.05 (2.84)
6.30 (2.53)
-1.25 (-1.92 to -0.58)
.0003
12-Month follow-up
4.96 (2.75)
6.48 (2.43)
-1.52 (-2.16 to -0.87)
<.0001
Baseline
6.62 (1.85)
6.77 (1.74)
-0.15 (-0.60 to 0.30)
.51
6-Month follow-up
5.04 (2.57)
6.14 (2.31)
-1.11 (-1.72 to -0.50)
.0004
12-Month follow-up
4.94 (2.54)
6.33 (2.18)
-1.39 (-1.98 to -0.80)
<.0001
6-Month follow-up
47 (38.2)
22 (17.3)
2.2 (1.4 to 3.0)
.0002
12-Month follow-up
51 (41.5)
22 (17.3)
2.4 (1.6 to 3.2)
<.0001
6-Month follow-up
29 (23.6)
10 (7.9)
3.0 (1.6 to 5.1)
.0006
12-Month follow-up
32 (26.0)
10 (7.9)
3.3 (1.8 to 5.4)
.0001
Depression outcomes
SCL-20 depression (range, 0-4)
Major depressive disorder, n (%)
Depression responder ( 50% decrease in

SCL-20 from baseline), n (%)
Pain outcomes
Brief Pain Inventory severity (range, 0-10)
.92
Brief Pain Inventory interference (range, 0-10)
Brief Pain Inventory total (range, 0-10) *
Pain responder ( 30% decrease in BPI total

from baseline), n (%)
Composite outcome
Composite responder ( 50% decrease in
SCL-20 and 30% decrease in BPI total from
baseline), n (%)
BPI total is the average of the 11 items of the BPI severity (4 items) and BPI interference (7 items) scales.
Kroenke et al.
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Table 3
Secondary Pain and Quality of Life Outcomes (Last-Observation Carried Forward)
Clinical Outcome
Intervention (123)
Usual Care (127)
Between-Group Difference
(95% CI)
P value
Baseline
17.3 (4.5)
17.6 (4.1)
-0.3 (-1.4 to 0.8)
.57
12-Month follow-up
14.0 (6.5)
17.2 (5.3)
-3.2 (-4.7 to -1.8)
<.0001
Baseline
72.7 (17.7)
72.8 (15.4)
-0.1 (-4.2 to 4.1)
.97
12-Month follow-up
67.8 (22.8)
74.7 (17.2)
-6.9 (-12.0 to -1.9)
.007
Baseline
67.8 (25.0)
70.2 (24.8)
-2.4 (-8.6 to 3.8)
.45
12-Month follow-up
52.5 (31.6)
66.1 (27.3)
-13.6 (-20.9 to -6.2)
Baseline
34.9 (33.4)
38.0 (33.1)
-3.1 (-11.4 to 5.2)
.46
3-Month follow-up
33.2 (32.3)
41.5 (33.2)
-8.3 (-16.5 to -0.1)
.046
6-Month follow-up
28.2 (31.5)
31.1 (30.9)
-2.8 (-10.6 to 5.0)
.47
12-Month follow-up
31.4 (33.2)
38.1 (31.8)
-6.8 (-14.9 to 1.3)
.10
Baseline
8.7 (4.5)
9.1 (4.4)
-0.4 (-1.5 to 0.7)
.48
12-Month follow-up
5.8 (5.0)
8.0 (5.1)
-2.2 (-3.5 to -0.9)
.0007
Baseline
33.1 (27.9)
28.4 (26.6)
4.7 (-2.1 to 11.5)
.18
12-Month follow-up
35.2 (29.7)
24.2 (25.5)
11.1 (4.2 to 18.0)
.002
Baseline
38.0 (25.2)
40.5 (26.2)
-2.5 (-8.9 to 4.0)
.45
12-Month follow-up
53.1 (30.9)
47.0 (28.5)
6.1 (-1.3 to 13.5)
.11
Baseline
26.5 (16.0)
27.2 (14.1)
-0.7 (-4.5 to 3.0)
.70
12-Month follow-up
37.3 (21.1)
28.8 (16.9)
8.5 (3.8 to 19.1)
.0005
Baseline
25.8 (16.6)
24.6 (17.3)
1.2 (-3.0 to 5.4)
.57
12-Month follow-up
36.6 (22.7)
27.8 (18.9)
8.8 (3.6 to 14.0)
.001
Roland pain disability (range, 0-24)
Graded chronic pain scale (GCPS)

GCPS severity score (range, 0 to 100)
GCPS disability score (range, 0 to 100)
.0003
GCPS disability days from pain in past 3

months (range, 0 to 90)
GAD-7 anxiety score (range, 0-21)
SF functioning/quality of life (range, 0-100)

General health perceptions
Social functioning
Bodily pain
Vitality
2.6 (3.1)
1.3 (3.3)
Other
1.5 (5.8)
1.6 (7.9)
Mental health
1.8 (3.4)
2.7 (4.0)
Surgical specialty
Hospital days
1.3 (2.3)
Medical specialty
Emergency dept visits
6.4 (5.8)
Primary care
Outpatient visits
Health care use, number
3.5 (4.6)
0.7 (2.2)
Other psychotropics
Other analgesics
1.2 (2.7)
Opioid analgesics
9.3 (4.2)
Tricyclics
Mean (SD)
Antidepressants
Medication use, months
0 (0-49)
1 (0-27)
0 (0-23)
0 (0-82)
1 (0-24)
0 (0-16)
5 (0-35)
1 (0-12)
1 (0-12)
0 (0-12)
0 (0-12)
12 (0-12)
Median (Range)
Intervention (123)
0.8 (2.5)
1.2 (2.1)
1.3 (2.6)
0.7 (2.9)
2.4 (3.5)
1.6 (2.9)
5.8 (5.4)
2.8 (3.4)
3.0 (4.2)
0.7 (2.3)
1.2 (2.6)
2.0 (3.2)
Mean (SD)
0 (0-15)
0 (0-14)
0 (0-18)
0 (0-24)
1 (0-26)
0 (0-19)
4 (0-33)
1 (0-12)
1 (0-12)
0 (0-12)
0 (0-12)
0 (0-12)
Median (Range)
Usual Care (127)
< .0001
< .0001
.89
< .0001
.11
.02
.11
.57
.40
.93
.99
< .0001
P value *
The use of other analgesics may be underestimated since simple analgesics are often obtained without a prescription and would not be captured by electronic prescribing data.
Typically low-dose (< 100 mg amitriptyline or equivalent) rather than antidepressant dose level
Group differences on medication use were tested using t-test and on health care use using Poisson modeling.
Variable

Table 4

Kroenke et al.
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74 (60)
45 (37)
Other
25 (20)
31 (25)
Mental health
Time in hospital, d
77 (63)
Surgical specialty
61 (50)
52 (42)
Medical specialty
Emergency dept visits
115 (94)
Primary care
Outpatient visits
Health care use, No.
67 (54)
20 (16)
Other psychotropics
Other analgesics c
32 (26)
Tricyclics b
Opioid analgesics
121 (98)
Antidepressants
Medication use, mo
Intervention Group (n = 123)
18 (14)
59 (46)
53 (42)
21 (17)
86 (68)
53 (42)
119 (94)
82 (66)
67 (53)
16 (13)
35 (28)
54 (43)
Usual Care Group (n = 127)
No (%) of Patients with Any Use Over 12 Months
1.5 (5.9); 0 (0-49)
1.8 (3.5); 0 (0-27)
1.4 (3.4); 0 (0-23)
1.6 (7.9); (0-82)
2.7(4.0); 1 (0-24)
1.3 (2.3); 0 (0-16)
6.3 (5.8) 5 (0-35)
2.5 (3.1); 1 (0-12)
3.5 (4.6); 1 (0-12)
0.7 (2.2); 0 (0-12)
1.2 (2.7); 0 (0-12)
9.2 (4.2); 12 (0-12)
Intervention Group (n = 123)
c
The use of other analgesics may be underestimated since simple analgesics are often obtained without a prescription and would not be captured by electronic prescribing data.
Typically low-dose (< 100 mg amitriptyline or equivalent) rather than antidepressant dose level
0.8 (2.5); 0 (0-15)
1.2 (2.1); 0 (0-14)
1.2 (2.4); 0 (0-18)
0.7 (2.9); 0 (0-24)
2.4 (3.5); 1 (0-26)
1.6 (2.8); 0 (0-19)
5.9 (5.3); 4 (0-33)
2.8 (3.4); 1 (0-12)
3.0 (4.2); 1 (0-12)
0.7 (2.2); 0 (0-12)
1.2 (2.6); 0 (0-12)
2.0 (3.3); 0 (0-12)
Usual Care Group (n = 127)
Amount of Use in Entire Sample Over 12 Months Mean (SD); Median (Range)
Differences between group means were compared using t-test for amount of medication use and Poisson modeling for amount of health care use
Variable

Table 5
< .001
< .001
.16
< .001
.10
.03
.16
.44
.35
.89
.98
< .001
P Value a

Kroenke et al.
Page 23
Avoid if cardiovascular disease, abnormal ECG, or hypertension not well controlled
SSRI of choice
SSRI of choice if cardiovascular disease
If failed first SSRI (fluoxetine or sertraline)
If obese or weight gain/sexual side effects
If insomnia a problem. Avoid if obese.
Avoid if cardiovascular disease, abnormal ECG, or hypertension not well controlled
TCA
Other
SSRI
SNRI
Nortriptyline
Mirtazapine
Bupropion
Citalopram
Sertraline
Fluoxetine
Venlafaxine
Drug
25
15
200
20
50
20
75
50, 75
30, 45
300, 400
30, 40
100, 150
30, 40
150, 225
Dose Increases
Dose (in mg)

Initial
SNRI = serotonin-norepinephrine reuptake inhibitor. SSRI = selective serotonin reuptake inhibitor. TCA = tricyclic antidepressant.
Indications and Precautions
Class*
Priority
Appendix. Antidepressant Selection and Dosing Details in SCAMP

Kroenke et al.
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Optimized Antidepressant Therapy and Pain Self-Management in

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Main Outcome MeasuresAssessments at baseline, 1, 3, 6, and 12 months for depression

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Step 2: Pain Self-Management (PSM) Program (Weeks 13-26)The PSM sessions

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Step 3: Continuation Phase (Weeks 27-52)Intervention patients received scheduled

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Care Manager Contacts and Antidepressants Used in the Intervention Group

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The antidepressant initiated or continued at baseline was venlafaxine in 75 (61%) of the

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