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 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. 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 I mproving outcomes for depressed patients depends in part on understanding the predictors of treatment response. De- spite advances in antidepressant treatment, including the emergence of selective serotonin reuptake inhibitors (SSRIs) and other newer agents, treatment response remains subopti- mal. 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 sig- nificantly more severe and chronic course of depression (3). Patients with depressive disorders often manifest multiple complaints, including an overlapping constellation of emo- tional and physical symptoms. Physical symptoms (eg, fa- tigue, insomnia, pain) are more numerous in depressed pa- tients, 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 phys- ical complaints only (7–9), and at least 60% of these com- plaints are pain-related (10 –12). Physical symptoms, espe- cially 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 ac- tivity) are exaggerated when depression and pain coexist (18). Furthermore, pain severity and frequency, pain-related func- tional 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 antidepres- sant therapy. METHODS 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, physi- cians 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 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, Ar- lington, 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@regenstrief.org Received for publication May 14, 2003. 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 ac- complished this review in less than 30 days and had no modifications to suggest for the manuscript. DOI: 10.1097/01.PSY.0000106883.94059.C5 17 Psychosomatic Medicine 66:17–22 (2004) 0033-3174/04/6601-0017 Copyright © 2004 by the American Psychosomatic Society