Psychosomatic Medicine
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bair, M. J.
Right arrow Articles by Kroenke, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bair, M. J.
Right arrow Articles by Kroenke, K.
Related Collections
Right arrow Pain
Right arrow Depression
Right arrow Psychophysiology
Psychosomatic Medicine 66:17-22 (2004)
© 2004 American Psychosomatic Society

ORIGINAL ARTICLES

Impact of Pain on Depression Treatment Response in Primary Care

Matthew J. Bair, MD, MS, Rebecca L. Robinson, MS, George J. Eckert, MAS, Paul E. Stang, PhD, Thomas W. Croghan, MD and Kurt Kroenke, MD

From the Regenstrief Institute and the Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana (M.J.B., G.J.E., T.W.C., K.K.); Eli Lilly and Co., Indianapolis, Indiana (R.L.R.); Rand Health, Arlington, Virginia (T.W.C.); and Galt Associates Adjunct and the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (P.E.S.).

Matthew J. Bair, MD, Regenstrief Institute, Inc., RG-6, 1050 Wishard Blvd., Indianapolis, IN 46202. E-mail: mbair{at}regenstrief.org


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
OBJECTIVE: Pain commonly coexists with depression, but its impact on treatment outcomes has not been well studied. Therefore, we prospectively evaluated the impact of comorbid pain on depression treatment response and health-related quality of life.

METHODS: We analyzed data from the ARTIST study, a randomized controlled trial with naturalistic follow-up conducted in 37 primary care clinics. Participants were 573 clinically depressed patients randomized to one of three selective serotonin reuptake inhibitor (SSRI) antidepressants: fluoxetine, paroxetine, or sertraline. Depression as assessed by the Symptom Checklist-20 (SCL-20) was the primary outcome. Secondary outcomes included pain and health-related quality of life.

RESULTS: Pain was reported by more than two thirds of depressed patients at baseline, with the severity of pain mild in 25% of patients, moderate in 30%, and severe in 14%. After 3 months of antidepressant therapy, 24% of patients had a poor depression treatment response (ie, SCL-20 >1.3). Multivariate odds ratios for poor treatment response were 1.5 (95% confidence interval, 0.8–3.2) for mild pain, 2.0 (1.1–4.0) for moderate pain, and 4.1 (1.9–8.8) for severe pain compared with those without pain. Increasing pain severity also had an adverse impact on outcomes in multiple domains of health-related quality of life.

CONCLUSIONS: Pain is present in two thirds of depressed primary care patients begun on antidepressant therapy, and the severity of pain is a strong predictor of poor depression and health-related quality of life outcomes at 3 months. Better recognition, assessment, and treatment of comorbid pain may enhance outcomes of depression therapy.

Key Words: depression, • pain, • treatment response, • primary care.

Abbreviations: ARTIST = A Randomized Trial Investigating SSRI Treatment;; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th Edition;; HRQL = health-related quality of life;; PHQ-15 = Patient Health Questionnaire somatic symptom severity scale-15;; PRIME-MD = Primary Care Evaluation of Mental Disorders;; SCL-20 = Symptom Checklist-20;; SF-36 = Medical Outcomes Study Short Form-36;; SSRI = selective serotonin reuptake inhibitor.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Improving outcomes for depressed patients depends in part on understanding the predictors of treatment response. Despite advances in antidepressant treatment, including the emergence of selective serotonin reuptake inhibitors (SSRIs) and other newer agents, treatment response remains suboptimal. Between 50% and 70% of depressed patients experience a partial response to medications, and only 30% of patients achieve complete resolution of their depressive symptoms (1,2). Incomplete recovery has been shown to predict a significantly more severe and chronic course of depression (3).

Patients with depressive disorders often manifest multiple complaints, including an overlapping constellation of emotional and physical symptoms. Physical symptoms (eg, fatigue, insomnia, pain) are more numerous in depressed patients, frequently nonspecific (4,5), often unrelated to a known organic disease process (6), and lead to greater health care utilization. More than 50% of depressed patients report physical complaints only (7–9), and at least 60% of these complaints are pain-related (10–12). Physical symptoms, especially pain, negatively impact recognition of depression (7,8), adherence to medication (13), and adequate therapy (14). As a result, poor depression treatment outcomes are likely (eg, failure to achieve remission). Patients who fail to achieve remission after antidepressant therapy are more likely to suffer residual pain and other physical symptoms compared with the patients that remit (15).

Impairments in social function (16), work function (17), and functional limitations (eg, limited mobility, restricted activity) are exaggerated when depression and pain coexist (18). Furthermore, pain severity and frequency, pain-related functional impairment, and diffuse pain are all associated with more depressive symptoms and more severe depression (19,20). What is not clear is whether patients with depression and pain are less responsive to usual depression management than patients with depression alone. Therefore, we sought to determine whether the presence and severity of baseline pain is associated with poor depression treatment response and health-related quality of life (HRQL) outcomes in a cohort of depressed primary care patients started on SSRI antidepressant therapy.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Data Source
The source of data was A Randomized Trial Investigating SSRI Treatment (ARTIST) (21), a naturalistic (ie, real world), randomized trial designed to compare the effectiveness of three SSRIs (fluoxetine, paroxetine, sertraline) in clinically depressed patients. To emulate typical clinical practice, physicians were allowed to alter patient treatment strategies (eg, switch to any other antidepressant, titrate the starting dose, augment with other antidepressants) if the patient did not adequately respond to or tolerate the initial SSRI. Patients were followed regardless of their treatment patterns. Pharmacy benefit cards that covered the costs of all antidepressants were provided to patients to reduce the financial and access barriers associated with medication adherence. All patients in ARTIST were 18 years of age or older and had a home telephone, and a SSRI was deemed appropriate for depression treatment by their primary care physician. Exclusion criteria included (1) cognitive impairment; (2) bipolar depression; (3) active substance abuse; (4) terminal illness; (5) residence in a nursing home; (6) pregnancy, planned pregnancy, or breastfeeding; (7) inability to communicate in English; (8) active suicidal ideation; (9) current or recent use of SSRIs; (10) other antidepressant use at higher than low doses (eg, >50 mg of amitriptyline or its equivalent) either for depression or for a nondepressive disorder (eg, insomnia); or (11) ineligibility for starting doses of fluoxetine (20 mg/d), paroxetine (20 mg/d), or sertraline (50 mg/d).

A total of 573 patients from two US primary care research networks, including 37 clinics, were randomized to one of the SSRI antidepressants and evaluated with a battery of depression, social and work functioning, and other HRQL measures. Patients were screened and randomized during a visit to the primary care provider. Computer-assisted telephone interviews were used to collect baseline data and outcomes at 1, 3, 6, and 9 months. Treatment effectiveness was evaluated by the change in depression and psychological measures at each interval and compared across treatment groups. As originally reported, the three SSRIs demonstrated similar effectiveness for depressive symptoms and all HRQL and secondary outcomes over the entire 9 months of the trial (21). For the present article, baseline and 3-month data were analyzed because the focus was on acute-phase (ie, 3-month) depression response as opposed to maintenance treatment response. A total of 504 patients (88% response rate) participated in the 3-month interview, and complete data were available for 501.

Study Measures
The primary outcome was the Symptom Checklist-20 (SCL-20) depression severity scale, a modified subscale of the Hopkins Symptom Checklist and Brief Symptom Inventory. This scale has been used extensively to assess depression outcomes in primary care trials (22–25). The 20 items are scored from 0 to 4 and averaged to provide a measure of overall severity from 0 to 4, with higher scores representing more severe depression. The Primary Care Evaluation of Mental Disorders (PRIME-MD) depression module (26) was used to classify patients according to DSM-IV diagnostic subgroups of major depression, dysthymia, and minor depression.

Health-related quality of life outcomes were assessed at baseline and 3-month follow-up by the Medical Outcomes Study Short Form-36 (SF-36) subscales: general health, mental health, physical functioning, role functioning—physical, role functioning—emotional, social functioning, and vitality (27). The SF-36 bodily pain subscale was included as an independent variable (instead of an outcome variable) as described below.

Two different pain scales were used. The SF-36 bodily pain subscale provides a composite score ranging from 0 (worst) to 100 (best) health status. The scale consists of two items that were also analyzed separately to address the individual contributions of pain severity and pain interference (ie, how much pain interferes with a person’s function at work or at home). The Patient Health Questionnaire somatic symptom severity scale-15 (PHQ-15) measures how much a patient is bothered by 15 different physical symptoms in the last month (28). The PHQ-15 assesses the bothersomeness of five specific pain symptoms: headaches, back pain, limb or joint pain, abdominal pain, and chest pain. The five pain items are summed to provide a composite pain score ranging from 0 to 10, with higher scores indicating more pain. Additionally, each of the pain symptoms were analyzed separately. For analysis purposes, we operationalized pain items from both the SF-36 and the PHQ-15 scales into four pain severity classes. The SF-36 pain severity item responses were categorized as follows: "none" or "very mild" = none, "mild" = mild, "moderate" = moderate, and "severe" or "very severe" = severe pain. PHQ-15 pain scale scores were likewise categorized as none (0–2), mild (3–4), moderate (5–6), and severe (7–10). Finally, the PHQ-15 also assesses 10 nonpain somatic symptoms, producing a severity score of 0 to 20.

Data Analysis
Data were analyzed using SAS Version 8.2 (SAS Institute, Cary, NC). Multivariate logistic and linear regression modeling were used to assess the independent effect of baseline pain on depression outcomes and, secondarily, HRQL outcomes. To account for possible correlations between patients seen by the same physician or by different physicians in the same clinic, we included physician and clinic as random effects in the models.

For logistic regression, the SCL-20 depression score at 3 months was dichotomized at a cutpoint of 1.3. Patients with scores greater than 1.3 (ie, more severe depression) were defined as poor depression treatment responders. This SCL-20 cutpoint was chosen for three reasons: (1) it is a cutpoint used in a previous primary care depression trial (23); (2) improvements to this level by 3 months represented an average effect size of less than 0.5, a minimal threshold for categorizing health status changes as at least moderate in magnitude (29); and (3) it defined the upper quartile (ie, most severe depression) of patients at 3-month follow-up. For the secondary outcomes, we defined poor HRQL at 3 months as being within the lowest 25th percentile for each domain. Separate models were run for each of the seven SF-36 subscales (excluding bodily pain), with the dependent variable being the specific SF-36 domain and the predictor variable being baseline pain severity as measured by the SF-36 pain severity item and categorized as none, mild, moderate, or severe pain. Odds ratios and 95% confidence intervals were computed while controlling for age, gender, race, initial SSRI assignment (intent to treat with fluoxetine, paroxetine, or sertraline), clinic site, treating physician, nonpain somatic symptom severity, and baseline score of the dependent variable (ie, depression or relevant HRQL domain).

In linear regression models, the dependent variable was the change in SCL-20 depression score from baseline to 3-month follow-up. The predictor variable tested was again baseline SF-36 bodily pain, controlling for the same covariates. Finally, the consistency of our results was examined by creating additional models with the same depression and HRQL outcomes and covariates, but replacing the pain predictor variable with our secondary pain measures: the PHQ-15 pain subscale, the individual SF-36 items of pain severity and pain interference, and the severity of each of the five specific PHQ-15 pain symptoms.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
The 573 study patients had a mean age of 46 years, were 79% women, and had a racial distribution of 84% white, 13% black, and 3% other. Baseline and 3-month depression, pain, and HRQL measures are shown in Table 1. Mean SCL-20 depression score was 1.66 at baseline, representing moderately severe depression and consistent with SCL-20 scores reported in previous primary care depression trials (23,30). On average, patients responded well, improving to a mean SCL-20 of 0.9 by 3 months. However, 24% had persistently elevated scores (ie, SCL-20 scores >1.3) at 3 months and were defined as poor responders. Nearly three fourths (73%) of the patients met DSM-IV criteria for major depression at baseline (most of the rest had dysthymia), whereas the proportion with major depression declined to 32% by 3 months.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Depression, Pain, and HRQL at Baseline and 3 Months
 
Over two thirds (69%) of patients reported some degree of pain on the baseline SF-36 pain severity item, with the distribution of mild, moderate, and severe pain 25%, 30%, and 14%, respectively. By 3 months, the overall proportion with pain had declined slightly to 58%. For individual PHQ-15 pain symptoms, the proportion of patients who reported being "bothered a lot" ranged from 7% for chest pain to 33% for headache. Table 2 illustrates the strong baseline relationship between increasing pain severity and worse depression and poorer HRQL across all domains. A similar relationship was found when using the PHQ-15 pain scale to classify baseline pain severity. Because older age and female gender also had a modest association with increased pain severity, these were included as covariates in all analyses.


View this table:
[in this window]
[in a new window]
  		TABLE 2. Relation Between Baseline Pain Severity and Patient Characteristics
 
Baseline pain severity was a strong predictor of depression treatment outcomes, whether measuring pain with the SF-36 or PHQ-15 (Figure 1). In particular, the odds of a poor depression treatment response were twice as high in patients with moderate pain at baseline and three to four times as high in those with severe pain. These logistic regression models used patients without pain as the reference group and controlled for demographics (age, gender, and race) and other covariates (SSRI type, clinic site, treating physician, nonpain somatic symptoms, and baseline SCL-20 depression score). The strongest predictor in this model was baseline depression severity. A similar relation between increased baseline pain severity and worse 3-month HRQL outcomes was demonstrated across all SF-36 domains (Figure 2). The effect was most pronounced for the general health scale, but for most HRQL domains, each incremental increase in pain severity typically doubles the odds of a poor HRQL outcome.



View larger version (31K):
[in this window]
[in a new window]
  		Fig. 1. Increased risk of poor depression treatment response at 3 months according to baseline pain severity. Odds ratios were estimated by logistic regression models using patients without pain as the reference group and are statistically significant for moderate and severe pain.

 


View larger version (22K):
[in this window]
[in a new window]
  		Fig. 2. Increased risk of poor health-related quality of life outcomes at 3 months, defined as the lowest quartile for each SF-36 scale. Odds ratios were estimated by logistic regression models as described in Figure 1.

 
Depression outcome was also examined as a continuous variable (ie, change in SCL-20 score) in linear regression models, controlling for the same demographics and covariates used in the logistic models. As shown in Table 3, increased baseline pain severity, measured in a variety of ways, and less improvement in pain over a period of 3 months were strongly associated with worse depression treatment outcomes. Other predictors of worse depression outcome included baseline depression severity, older age, and the severity of nonpain somatic symptoms.


View this table:
[in this window]
[in a new window]
  		TABLE 3. Predictors of Worse Depression Treatment Response at 3 Months Measured as a Continuous Variablea
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
ACKNOWLEDGMENTS
 REFERENCES
 
Our analysis of data from the ARTIST trial demonstrates the high prevalence of pain (69%) in depressed primary care patients beginning antidepressant therapy and the adverse impact of such pain on treatment response. Both depression and multiple HRQL outcomes are worse in patients with comorbid pain, and there is an incremental impact with increasing pain severity. These findings are consistent across a variety of ways of measuring pain and are demonstrable whether depression and pain are measured as categorical or as continuous variables.

Most studies demonstrating a high prevalence of pain symptoms in depressed patients have been conducted in psychiatric or other specialty (eg, pain clinic) settings (31–34). However, a few studies situated in primary care settings have reported a 43% to 65% prevalence of pain symptoms in depressed patients (10,35,36). The fact that depressed patients in the ARTIST trial were all judged to have depression severe enough to warrant antidepressant therapy may account for a pain prevalence in the upper range.

In addition, the specific complaints of headache, back pain, abdominal pain, joint pain, and chest pain are frequently endorsed by depressed patients in primary care settings (11,12). The common co-occurrence of depression and pain symptoms is one reason that depression is frequently unrecognized and therefore untreated in primary care. The somatic symptoms often predominate and may distract attention from comorbid depressive symptoms. The new emphasis on pain as the "fifth vital sign" by both the Joint Commission on Accreditation of Healthcare Organizations and the Veterans Health Administration provides an opportunity for better recognizing and understanding the interaction between depression and pain.

Most depression and pain studies have either been cross-sectional or have assessed the adverse impact of comorbid depression on pain outcomes. Relatively fewer studies have addressed the converse: how the presence of pain affects depression response and other secondary outcomes such as functional status, quality of life, and health care costs and utilization. In this regard, several studies by Von Korff et al. (19) have been informative. They found that the presence of as many as five different pain complaints (abdominal pain, headache, back pain, chest pain, and facial pain) is associated with increased depressive symptoms. Similar to our findings, the findings of Von Korff et al. (18) showed that progressive baseline pain severity was associated with more severe depression. Additionally, they demonstrated that increased pain severity was related to more pain-related functional limitations, worse self-rated health, higher unemployment rates, more frequent use of opiate analgesics, and more pain-related doctor visits (at baseline and 1 year follow-up) (18).

A sample of depressed patients experienced pain on more than half the days over a 3-month period and produced 16 days when usual activities were curtailed, 4 days missed from school or work, and at least one visit with a physician or clinical nurse (37). Pain that interferes with daily activities, the number of days in pain (within a 6-month period), and the diffuseness of pain (or number of pain sites) all predict depression severity (20). Depression is associated with failure of back pain to improve at both short-term (7 weeks) and long-term (2 years) follow-up (18,38,39). Additionally, depressive symptoms may improve substantially with a reduction in pain (19).

A few studies have suggested that depressed patients with comorbid chronic low back pain respond just as well (ie, fewer depression symptoms) to antidepressants and cognitive behavioral therapy as depressed patients without back pain (40,41). In contrast, our data from a large randomized clinical trial suggest that baseline pain reduces the benefits of antidepressant therapy at 3 months, both in terms of depression and HRQL outcomes.

Some study limitations warrant mention. For one, we cannot infer a direct cause and effect relation between pain and poor depression outcomes. The ARTIST trial was designed primarily to test the relative effectiveness of three SSRI antidepressants on a variety of depression, HRQL, work, and social functioning outcomes. Our findings regarding the impact of pain on treatment response arise from secondary analysis of this trial and should be confirmed in further studies. Second, we did not measure other variables that may enrich our understanding, such as duration of pain, pain medication use, and which symptoms arose first—depression or pain.

Nonetheless, our study demonstrates the substantial co-occurrence of depression and pain symptoms and the impact of the latter on depression treatment response. We believe a treatment model that incorporates assessment and treatment of both depression and pain is desirable. However, more research is needed to determine whether alleviation of pain helps the patients’ depressive symptoms and, likewise, whether relief of depressive symptoms improves pain and its related morbidity or whether a common third factor is related to the severity and response of both pain and depression. In the future, dual therapy trials are needed to assess whether adequate treatment of both depression and pain, rather than an exclusive focus on one or the other, improves patient outcomes.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
REFERENCES
 
The authors gratefully acknowledge the efforts of the ARTIST study investigators, whose names are detailed in the original report (21). This research was supported in part by Grant T-32 PE15001 from the Health Resources and Service Administration and by funding from Eli Lilly and Co., Indianapolis, Indiana. This study was sponsored through a grant from Eli Lilly and Co. Two researchers (R.L.R., T.W.C.) employed by Eli Lilly and Co. were members of the group that designed the study. Data analysis was conducted by a statistician at Indiana University (G.J.E.), not the sponsor. The research contract permitted the investigators to publish the data without mandatory approval by the sponsor. The sponsor did have as long as 60 days to review the manuscript and provide feedback. However, the sponsor accomplished this review in less than 30 days and had no modifications to suggest for the manuscript.

Received for publication May 14, 2003.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 

  1. Fawcett J. Antidepressants: partial response in chronic depression. Br J Psychiatry Suppl 1994; 26: 37–41.
  2. O’Reardon JR. Treatment-resistant depression: progress and limitations. Psychiatric Ann 1998; 28: 633–40.
  3. Judd LL, Paulus MJ, Schettler PJ, Akiskal HS, Endicott J, Leon AC, Maser JD, Mueller T, Solomon DA, Keller MB. Does incomplete recovery from first lifetime major depressive episode herald a chronic course of illness? Am J Psychiatry 2000; 157: 1501–4.[Abstract/Free Full Text]
  4. Kirmayer LJ, Robbins JM. Three forms of somatization in primary care: prevalence, co-occurrence, and sociodemographic characteristics. J Nerv Ment Dis 1991; 179: 647–55.[Medline]
  5. Pearson SD, Katzelnick DJ, Simon GE, Manning WG, Helstad CP, Henk HJ. Depression among high utilizers of medical care. J Gen Intern Med 1999; 14: 461–8.[CrossRef][Medline]
  6. Kroenke K. Studying symptoms: sampling and measurement issues. Ann Intern Med 2001; 134: 844–53.[Abstract/Free Full Text]
  7. Bridges KW, Goldberg DP. Somatic presentation of DSM III psychiatric disorders in primary care. J Psychosom Res 1985; 29: 563–9.[CrossRef][Medline]
  8. Kirmayer LJ, Robbins JM, Dworkind M, Yaffe MJ. Somatization and the recognition of depression and anxiety in primary care. Am J Psychiatry 1993; 150: 734–41.[Abstract/Free Full Text]
  9. Simon GE, VonKorff M, Piccinelli M, Fullerton C, Ormel J. An international study of the relation between somatic symptoms and depression. N Engl J Med 1999; 341: 1329–35.[Abstract/Free Full Text]
  10. Hollifield M, Katon W, Morojele N. Anxiety and depression in an outpatient clinic in Lesotho, Africa. Int J Psychiatry Med 1994; 24: 179–88.[Medline]
  11. Mathew RJ, Weinman ML, Mirabi M. Physical symptoms of depression. Br J Psychiatry 1981; 139: 293–6.[Abstract/Free Full Text]
  12. Kroenke K, Spitzer RL, Williams JBW, Linzer M, Hahn SR, deGruy IIIFV, Brody D. Physical symptoms in primary care: predictors of psychiatric disorders and functional impairment. Arch Fam Med 1994; 3: 774–9.[Abstract/Free Full Text]
  13. Keeley R, Smith M, Miller J. Somatoform symptoms and treatment nonadherence in depressed family medicine outpatients. Arch Fam Med 2000; 9: 46–54.[Abstract/Free Full Text]
  14. Fritzsche K, Sandholzer H, Brucks U, Cierpka M, Deter H-C, Härter M, Höger C, Richter R, Schmidt B, Larisch A, Wirsching M. Psychosocial care by general practitioners—where are the problems? results of a demonstration project on quality management in psychosocial primary care. Int J Psychiatry Med 1999; 29: 395–409.[CrossRef][Medline]
  15. Paykel ES, Ramana R, Cooper Z, Hayhurst H, Kerr J, Barocka A. Residual symptoms after partial remission: an important outcome in depression. Psychol Med 1995; 25: 1171–80.[Medline]
  16. Holroyd KA, Stensland M, Lipchik GL, Hill KR, O’Donnell FS, Cordingley G. Psychosocial correlates and impact of chronic tension-type headaches. Headache 2000; 40: 3–16.[CrossRef][Medline]
  17. Dolce JJ, Crocker MF, Doleys DM. Prediction of outcome among chronic pain patients. Behav Res Ther 1986; 24: 313–9.[CrossRef][Medline]
  18. Von Korff M, Ormel J, Katon W, Lin EH. Disability and depression among high utilizers of health care: a longitudinal analysis. Arch Gen Psychiatry 1992; 49: 91–100.[Abstract/Free Full Text]
  19. Von Korff M, Dworkin SF, Le Resche L, Kruger A. An epidemiologic comparison of pain complaints. Pain 1988; 32: 173–83.[CrossRef][Medline]
  20. Von Korff M, Simon G. The relationship between pain and depression. Br J Psychiatry Suppl 1996; 30: 101–8.
  21. Kroenke K, West SL, Swindle R, Gilsenan A, Eckert GJ, Dolor R, Stang P, Zhou X-H, Hays R, Weinberger M. Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. JAMA 2001; 286: 2947–55.[Abstract/Free Full Text]
  22. Katon W, Robinson P, Von Korff M, Lin E, Bush T, Evette L, Simon G, Walker E. A multifaceted intervention to improve treatment of depression in primary care. Arch Gen Psychiatry 1996; 53: 924–32.[Abstract/Free Full Text]
  23. Katon W, Von Korff M, Lin E, Walker E, Simon GE, Bush T, Robinson P, Russo J. Collaborative management to achieve treatment guidelines: impact on depression in primary care. JAMA 1995; 273: 1026–31.[Abstract/Free Full Text]
  24. Simon GE, Revicki D, VonKorff M. Telephone assessment of depression severity. J Psychiatr Res 1993; 27: 247–52.[CrossRef][Medline]
  25. Unützer J, Katon W, Callahan CM, Williams , JrJW, Hunkeler E, Harpole L, Hoffing M, Della Penna RD, Hitchcock-Noël P, Lin EHB, Areán PA, Hegel MT, Tang L, Belin TR, Oishi S, Langston C. Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial. JAMA 2002; 288: 2836–45.[Abstract/Free Full Text]
  26. Spitzer RL, Williams JBW, Kroenke K, Linzer M, deGruy IIIFV, Hahn SR, Brody D, Johnson JG. Utility of a new procedure for diagnosing mental disorders in primary care: the PRIME-MD 1000 study. JAMA 1994; 272: 1749–56.[Abstract/Free Full Text]
  27. Ware JE Jr. SF-36 Health Survey: Manual and Interpretation Guide. Boston: Health Institute, New England Medical Center; 1993.
  28. Kroenke K, Spitzer RL, Williams JB. The PHQ-15: validity of a new measure for evaluating the severity of somatic symptoms. Psychosom Med 2002; 64: 258–66.[Abstract/Free Full Text]
  29. Kazis LE, Anderson JJ, Meenan RF. Effect sizes for interpreting changes in health status. Med Care 1989; 27: S178–89.
  30. Lin EHB, Simon GE, Katon WJ, Russo JE, Von Korff M, Bush TM, Ludman EJ, Walker EA. Can enhanced acute-phase treatment of depression improve long-term outcomes? a report of randomized trials in primary care. Am J Psychiatry 1999; 156: 643–5.[Abstract/Free Full Text]
  31. Delaplaine R, Ifabumuyi OI, Merskey H, Zarfas J. Significance of pain in psychiatric hospital patients. Pain 1978; 4: 361–6.[CrossRef][Medline]
  32. Merskey H, Spear FG. The concept of pain. J Psychosom Res 1967; 11: 59–67.[CrossRef][Medline]
  33. Diamond S. Depressive headaches. Headache 1964;October: 255–9.
  34. von Knorring L, Perris C, Eisemann M, Eriksson U, Perris H. Pain as a symptom in depressive disorders, I: relationship to diagnostic subgroup and depressive symptomatology. Pain 1983; 15: 19–26.
  35. Lindsay PG, Wyckoff M. The depression-pain syndrome and its response to antidepressants. Psychosomatics 1981; 22: 571–3.[Abstract/Free Full Text]
  36. Vaeroy H, Merskey H. The prevalence of current major depression and dysthymia in a Norwegian general practice. Acta Psychiatr Scand 1997; 95: 324–8.[Medline]
  37. Russo J, Katon W, Lin E, Von Korff M, Bush T, Simon G, Walker E. Neuroticism and extraversion as predictors of health outcomes in depressed primary care patients. Psychosomatics 1997; 38: 339–48.[Abstract/Free Full Text]
  38. Cherkin DC, Deyo RA, Street JH, Barlow W. Predicting poor outcomes for back pain seen in primary care using patients’ own criteria. Spine 1996; 21: 2900–7.[CrossRef][Medline]
  39. Von Korff M, Deyo RA, Cherkin D, Barlow W. Back pain in primary care: outcomes at 1 year. Spine 1993; 18: 855–62.[Medline]
  40. Rickels K, Smith WT, Glaudin V, Amsterdam JB, Weise C, Settle GP. Comparison of two dosage regimens of fluoxetine in major depression. J Clin Psychiatry 1985; 46: 38–41.[Medline]
  41. Elkin I, Shea MT, Watkins JT, Imber SD, Sotsky SM, Collins JF, Glass DR, Pilkonis PA, Leber WR, Docherty JP. National Institute of Mental Health Treatment of Depression Collaborative Research Program. General effectiveness of treatments. Arch Gen Psychiatry 1989; 46: 971–82.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 PsychosomaticsHome page
C. Han, C.-U. Pae, A. A. Patkar, P. S. Masand, K. W. Kim, S.-H. Joe, and I.-K. Jung
Psychometric Properties of the Patient Health Questionnaire-15 (PHQ-15) for Measuring the Somatic Symptoms of Psychiatric Outpatients
Psychosomatics, November 1, 2009; 50(6): 580 - 585.
[Abstract] [Full Text] [PDF]

Home page
 JBJSHome page
A.-M. Vranceanu, A. Barsky, and D. Ring
Psychosocial Aspects of Disabling Musculoskeletal Pain
J. Bone Joint Surg. Am., August 1, 2009; 91(8): 2014 - 2018.
[Abstract] [Full Text] [PDF]

Home page
 FocusHome page
J. F. Karp and C. F. Reynolds III
Depression, Pain, and Aging
Focus, January 1, 2009; 7(1): 17 - 27.
[Abstract] [Full Text] [PDF]

Home page
 PsychosomaticsHome page
L. Caballero, E. Aragones, J. Garcia-Campayo, F. Rodriguez-Artalejo, J. L. Ayuso-Mateos, P. Polavieja, E. Gomez-Utrero, I. Romera, and I. Gilaberte
Prevalence, Characteristics, and Attribution of Somatic Symptoms in Spanish Patients With Major Depressive Disorder Seeking Primary Health Care
Psychosomatics, November 1, 2008; 49(6): 520 - 529.
[Abstract] [Full Text] [PDF]

Home page
 Psychosom. Med.Home page
M. J. Bair, J. Wu, T. M. Damush, J. M. Sutherland, and K. Kroenke
Association of Depression and Anxiety Alone and in Combination With Chronic Musculoskeletal Pain in Primary Care Patients
Psychosom Med, October 1, 2008; 70(8): 890 - 897.
[Abstract] [Full Text] [PDF]

Home page
 J PsychopharmacolHome page
I. Anderson, I. Ferrier, R. Baldwin, P. Cowen, L Howard, G Lewis, K Matthews, R. McAllister-Williams, R. Peveler, J Scott, et al.
Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2000 British Association for Psychopharmacology guidelines
J Psychopharmacol, June 1, 2008; 22(4): 343 - 396.
[Abstract] [PDF]

Home page
 PsychosomaticsHome page
E. E. Krebs, B. N. Gaynes, G. Gartlehner, R. A. Hansen, P. Thieda, L. C. Morgan, A. DeVeaugh-Geiss, and K. N. Lohr
Treating the Physical Symptoms of Depression With Second-Generation Antidepressants: A Systematic Review and Metaanalysis
Psychosomatics, May 1, 2008; 49(3): 191 - 198.
[Abstract] [Full Text] [PDF]

Home page
 Home Health Care Management PracticeHome page
W. M. Marcil
The Hospice Nurse and Occupational Therapist: A Marriage of Expedience
Home Health Care Management Practice, December 1, 2006; 19(1): 26 - 30.
[Abstract] [PDF]

Home page
 Psychosom. Med.Home page
B. A. Arnow, E. M. Hunkeler, C. M. Blasey, J. Lee, M. J. Constantino, B. Fireman, H. C. Kraemer, R. Dea, R. Robinson, and C. Hayward
Comorbid depression, chronic pain, and disability in primary care.
Psychosom Med, March 1, 2006; 68(2): 262 - 268.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. PsychiatryHome page
R. PEVELER, C. KATONA, S. WESSELY, and C. DOWRICK
Painful symptoms in depression: under-recognised and under-treated?
The British Journal of Psychiatry, March 1, 2006; 188(3): 202 - 203.
[Abstract] [Full Text] [PDF]

Home page
 CephalalgiaHome page
C-I Hung, C-Y Liu, J-L Fuh, Y-Y Juang, and S-J Wang
Comorbid Migraine is Associated with a Negative Impact on Quality of Life in Patients with Major Depression
Cephalalgia, January 1, 2006; 26(1): 26 - 32.
[Abstract] [Full Text] [PDF]

Home page
 BMJHome page
Minerva
BMJ, February 21, 2004; 328(7437): 472 - 472.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bair, M. J.
Right arrow Articles by Kroenke, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bair, M. J.
Right arrow Articles by Kroenke, K.
Related Collections
Right arrow Pain
Right arrow Depression
Right arrow Psychophysiology

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS