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The Association of Depression and Pain with Health-Related Quality of Life, Disability, and Health Care Use in Cancer Patients

Open AccessPublished:June 28, 2010DOI:https://doi.org/10.1016/j.jpainsymman.2009.12.023

      Abstract

      Context

      Pain and depression are two of the most prevalent and treatable cancer-related symptoms, each present in at least 20%–30% of oncology patients.

      Objective

      To determine the associations of pain and depression with health-related quality of life (HRQL), disability, and health care use in cancer patients.

      Methods

      The Indiana Cancer Pain and Depression study is a randomized clinical trial comparing telecare management vs. usual care for patients with cancer-related pain and/or clinically significant depression. In this article, baseline data on patients enrolled from 16 urban or rural community-based oncology practices are analyzed to test the associations of pain and depression with HRQL, disability, and health care use.

      Results

      Of the 405 participants, 32% had depression only, 24% pain only, and 44% both depression and pain. The average Hopkins Symptom Checklist 20-item depression score in the 309 depressed participants was 1.64 (on 0–4 scale), and the average Brief Pain Inventory (BPI) severity score in the 274 participants with pain was 5.2 (on 0–10 scale), representing at least moderate levels of symptom severity. Symptom-specific disability was high, with participants reporting an average of 16.8 of the past 28 days (i.e., 60% of their days in the past four weeks) in which they were either confined to bed (5.6 days) or had to reduce their usual activities by 50% (11.2 days) because of pain or depression. Moreover, 176 (43%) participants reported being unable to work because of health-related reasons. Depression and pain had both individual and additive adverse associations with quality of life. Most patients were currently not receiving care from a mental health or pain specialist.

      Conclusion

      Depression and pain are prevalent and disabling across a wide range of types and phases of cancer, commonly co-occur, and have additive adverse effects. Enhanced detection and management of this disabling symptom dyad is warranted.

      Key Words

      Introduction

      Pain and depression are two of the most common and potentially treatable symptoms in cancer patients. Pain is present in 14%–100% of cancer patients, depending on the setting, and the prevalence of major depressive disorder is 10%–25%, with a similar range for clinically depressive symptoms.
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      and up to half of cancer patients depressed at baseline remain depressed at one-year follow-up.
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      Management of cancer symptoms: Pain, depression, and fatigue.
      Likewise, cancer pain often is undertreated.
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      Pain and its treatment in outpatients with metastatic cancer.
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      Although there is considerable research on the prevalence and impact of pain and depression as individual symptoms in cancer patients, as well as their frequent co-occurrence, there have been fewer studies on the independent and additive effects of pain and depression on health-related quality of life (HRQL) in the same patient population. Moreover, these studies have been limited by highly selected cancer patients, small sample size, and focus on a single HRQL outcome. For example, three studies focused on a desire for hastened death in terminally ill cancer patients; this outcome was associated with both depression and pain in one study
      • Mystakidou K.
      • Parpa E.
      • Katsouda E.
      • Galanos A.
      • Vlahos L.
      The role of physical and psychological symptoms in desire for death: a study of terminally ill cancer patients.
      but only depression in the other two studies.
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      Three studies examined the individual associations of pain and depression with HRQL but did not examine their relative and combined effect.
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      Depression and quality of life in cancer patients with and without pain: the role of pain beliefs.
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      • Wilking N.
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      Health related quality of life in different states of breast cancer.
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      • Marsh G.
      • Ling W.M.
      • et al.
      The symptom cluster of fatigue, pain, anxiety, and depression and the effect on the quality of life of women receiving treatment for breast cancer: a multicenter study.
      A study of 115 cancer survivors found differential effects of pain, depression, and other symptoms on various domains of HRQL.
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      • Kimura M.
      • Teixeira M.J.
      • et al.
      Impact of cancer-related symptom synergisms on health-related quality of life and performance status.
      The Indiana Cancer Pain and Depression (INCPAD) study is a clinical trial enrolling patients from community-based oncology practices who suffer from depression and/or cancer-related pain and randomizing them to telecare management or usual care. INCPAD is, therefore, a good study in which to study the individual and combined effects of pain and depression. Our primary hypothesis for this article is that pain and depression in patients with cancer have independent and synergistic associations with both increased disability and poorer HRQL in domains not directly related to pain and mental health. Secondarily, we hypothesize that pain and depression are associated with increased health care use.

      Methods

      Screening and Eligibility Interview

      Details of the INCPAD study methods have been previously reported.
      • Kroenke K.
      • Theobald D.
      • Norton K.
      • et al.
      Indiana Cancer Pain and Depression (INCPAD) Trial: design of a telecare management intervention for cancer-related symptoms and baseline characteristics of enrolled participants.
      Briefly, patients presenting for outpatient visits at one of the 16 urban and rural participating oncology practices in the state of Indiana between March 2006 and August 2008 were invited to complete a four-item depression and pain screener, consisting of the Patient Health Questionnaire two-item (PHQ-2) depression scale and the Short Form-36 (SF-36) Bodily Pain scale, both of which are well-validated measures for assessing depression and pain severity.
      • Kroenke K.
      • Spitzer R.L.
      • Williams J.B.
      The Patient Health Questionnaire-2: validity of a two-item depression screener.
      • Ware J.E.
      • Kosinski M.
      • Keller S.D.
      SF-36 physical and mental health summary scales: A user's manual.
      Patients who screened positive for pain (at least moderate pain severity or pain interference)
      • Ware J.E.
      • Kosinski M.
      • Keller S.D.
      SF-36 physical and mental health summary scales: A user's manual.
      • Bair M.J.
      • Robinson R.L.
      • Eckert G.J.
      • et al.
      Impact of pain on depression treatment response in primary care.
      or depression (PHQ-2 score ≥2)
      • Kroenke K.
      • Spitzer R.L.
      • Williams J.B.
      The Patient Health Questionnaire-2: validity of a two-item depression screener.
      and were potentially interested in the study underwent an eligibility interview.

      Depression

      Depression had to be of at least moderate severity, defined as a PHQ nine-item (PHQ-9) depression score of 10 or greater with either depressed mood and/or anhedonia being endorsed.
      • Kroenke K.
      • Spitzer R.L.
      • Williams J.B.W.
      The PHQ-9: validity of a brief depression severity measure.
      • Kroenke K.
      • Spitzer R.L.
      The PHQ-9: a new depression and diagnostic severity measure.
      • Ruo B.
      • Rumsfeld J.S.
      • Hlatky M.A.
      • et al.
      Depressive symptoms and health-related quality of life: the Heart and Soul Study.
      In previous studies, >90% of patients fulfilling this PHQ-9 criterion had major depression and/or dysthymia, and the remaining patients had clinically significant depression with substantial functional impairment.
      • Kroenke K.
      • Spitzer R.L.
      • Williams J.B.W.
      The PHQ-9: validity of a brief depression severity measure.
      • Kroenke K.
      • West S.L.
      • Swindle R.
      • et al.
      Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial.

      Pain

      Pain had to be 1) at least moderate in severity, defined as a Brief Pain Inventory (BPI) “worst pain in the past week” score of 6 or greater;
      • Cleeland C.S.
      • Gonin R.
      • Hatfield A.K.
      • et al.
      Pain and its treatment in outpatients with metastatic cancer.
      • Cleeland C.S.
      Pain assessment in cancer.
      • Williams L.S.
      • Jones W.J.
      • Shen J.
      • Robinson R.L.
      • Kroenke K.
      Outcomes of newly referred neurology outpatients with depression and pain.
      • Bair M.J.
      • Williams L.S.
      • Kroenke K.
      Association of the ‘5th vital sign’ (pain) and depression in primary care.
      2) persistent despite the use of one or more analgesics; and 3) cancer-related. Cancer-related is defined as pain occurring in the region of the primary tumor or cancer metastases and/or occurring after the onset of cancer treatment. Excluded were pre-existing pain conditions unrelated to cancer (e.g., migraine or tension headache, arthritis, back disorders, bursitis or tendonitis, injuries, and fibromyalgia).
      Excluded were individuals who 1) did not speak English, 2) had moderately severe cognitive impairment as defined by a validated six-item cognitive screener,
      • Callahan C.M.
      • Unverzagt F.W.
      • Hui S.L.
      • Perkins A.J.
      • Hendrie H.C.
      A six-item screener to identify cognitive impairment among potential subjects for clinical research.
      3) had schizophrenia or other psychosis, 4) had a disability claim currently being adjudicated for pain, 5) had depression directly precipitated by a cancer therapy for which depression is a well-known side effect (e.g., interferon and corticosteroids) and in whom short treatment duration and tolerable depression severity justify withholding antidepressant therapy, 6) were pregnant, or 7) were in hospice care.

      Study Measures

      Depression diagnoses were established with the PHQ-9, which, with several added questions, categorizes individuals into three Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic subgroups: major depression, dysthymia, and other depression.
      • Kroenke K.
      • Spitzer R.L.
      • Williams J.B.W.
      The PHQ-9: validity of a brief depression severity measure.
      Depression severity was assessed with the Hopkins Symptom Checklist 20-item (HSCL-20) depression scale,
      • Kroenke K.
      • West S.L.
      • Swindle R.
      • et al.
      Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial.
      • Unutzer J.
      • Katon W.
      • Callahan C.M.
      • et al.
      Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial.
      • Katon W.
      • Von Korff M.
      • Lin E.
      • et al.
      Stepped collaborative care for primary care patients with persistent symptoms of depression: a randomized trial.
      which had an excellent internal reliability (Cronbach's α=0.89) in our sample. Pain was assessed primarily with the BPI, which rates the severity of pain on four items (current, worst, least, and average pain in past week) and the interference in seven areas (mood, physical activity, work, social activity, relations with others, sleep, and enjoyment of life).
      • Cleeland C.S.
      • Gonin R.
      • Hatfield A.K.
      • et al.
      Pain and its treatment in outpatients with metastatic cancer.
      • Cleeland C.S.
      Measurement of pain by subjective report.
      • Williams L.S.
      • Jones W.J.
      • Shen J.
      • et al.
      Prevalence and impact of pain and depression in neurology outpatients.
      Internal reliability also was excellent for the BPI severity (α=0.79) and BPI interference (α=0.89) scales. The SF-36 Bodily Pain scale
      • Von Korff M.
      • Jensen M.P.
      • Karoly P.
      Assessing global pain severity by self-report in clinical and health services research.
      =0.73) provided a secondary measure of pain.
      HRQL was assessed with the SF-12 physical component summary (PCS) and mental component summary (MCS) scores
      • Ware Jr., J.
      • Kosinski M.
      • Keller S.D.
      A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity.
      =0.84 for both), as well as the SF-36
      • McHorney C.A.
      • Ware J.E.
      • Raczek A.E.
      The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs.
      • Ware J.E.
      • Gandek B.
      The SF-36 Health Survey: development and use in mental health research and the IQOLA Project.
      Mental Health scale (α=0.82), Vitality scale (α=0.75), and a single general health perceptions item that has shown to predict long-term health outcomes.
      • Idler E.L.
      • Benyamini Y.
      Self-rated health and mortality: a review of twenty-seven community studies.
      Functional status, an important aspect of HRQL, was further assessed with the three-item Sheehan Disability Scale (α=0.82) and a single-item overall quality-of-life measure.
      • Sheehan D.V.
      • Harnett-Sheehan K.
      • Raj B.A.
      The measurement of disability.
      • Unutzer J.
      • Williams J.W.
      • Callahan C.M.
      • et al.
      Improving primary care for depression in late life: the design of a multicenter randomized trial.
      In addition, disability days were assessed as the number of days during the preceding four weeks in which the patient was either in bed or had to reduce his/her work or usual activities by 50% or more.
      • Wagner E.H.
      • LaCroix A.Z.
      • Grothaus L.C.
      • Hecht J.A.
      Responsiveness of health status measures to change among older adults.
      • Rost K.
      • Nutting P.
      • Smith J.
      • Werner J.
      • Duan N.
      Improving depression outcomes in community primary care practice: a randomized trial of the quEST intervention. Quality Enhancement by Strategic Teaming.
      This total number of disability days could, therefore, range from 0 to 28. Anxiety severity was assessed by the seven-item Generalized Anxiety Disorder (GAD-7) scale
      • Spitzer R.L.
      • Kroenke K.
      • Williams J.B.
      • Lowe B.
      A brief measure for assessing generalized anxiety disorder: the GAD-7.
      • Kroenke K.
      • Spitzer R.L.
      • Williams J.B.W.
      • Monahan P.O.
      • Lowe B.
      Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection.
      =0.86) for which the score ranges from 0 to 21 and which has proven to be a good screener for the most common anxiety disorders seen in medical patients.
      Medication use (antidepressants, other psychotropics, and opioid and nonopioid analgesics) was extracted from each patient's oncology practice records. Also, patients were asked in the baseline interview about treatments they had received and practitioners they had seen for depression and/or pain. Self-reported health care use in the preceding three months of five types of health services was assessed: hospital days and visits to an outpatient physician, emergency department (ED), mental health professional, or complementary and alternative medicine (CAM) provider. Finally, in addition to gathering demographic information, medical comorbidity was assessed with a checklist of eight common medical disorders that have been shown to predict hospitalization and mortality.
      • Perkins A.J.
      • Kroenke K.
      • Unutzer J.
      • et al.
      Common comorbidity scales were similar in their ability to predict health care costs and mortality.

      Statistical Analysis

      Characteristics of the three patient groups (pain only, depression only, and pain and depression) were described, and bivariate comparisons were tested using analysis of variance for continuous variables and Chi-square analysis for categorical variables. Because these bivariate comparisons were not adjusted for multiple comparisons, any differences among groups that are not highly significant (P<0.001) should be interpreted cautiously. Depression- and pain-specific treatments also were described for the three groups without statistical comparisons.
      Our primary outcomes of interest were three HRQL domains (vitality, general health perceptions, and overall quality of life) and two measures of disability (Sheehan Disability score and number of disability days). The relationships of the three HRQL outcomes and the Sheehan Disability score to pain and depression were examined in multivariable linear regression models. The relationship of total number of disability days in the preceding four weeks to pain and depression was examined in a multivariable log-linear regression model based on Poisson distribution. The dependent variable in each model was one of the HRQL or disability outcomes. The independent variables were HSCL-20 depression and BPI pain severity scores. The covariates were age, sex, race (white and other), medical comorbidity, educational level (less than high school vs. high school education or higher), income (not enough to make ends meet vs. comfortable or just enough to make ends meet), and employment status (unemployed or unable to work for health or disability reasons vs. employed, retired, homemaker, or student).
      Multivariable models were run in four steps: pain only (Step 1), depression only (Step 2), pain and depression (Step 3), and pain and depression adjusting for covariates (Step 4). Steps 1 and 2 were run to explore the individual association of pain and depression with the outcomes. Step 3 aimed to determine the independent effects of pain and depression controlling for the presence of each other. Step 4 examined the independent effects of pain and depression while controlling for the effects of potential confounders. Results in the fully adjusted model (Step 4) were adjusted for multiple comparisons using a modified Bonferroni procedure.
      • Hochberg Y.
      A sharper Bonferroni procedure for multiple tests of significance.
      Secondarily, we explored differences among the three symptom groups in the five patient-reported measures of health care use. Because health care use was reported in ordinal categories, group differences were compared by Chi-square analysis and adjusted for multiple comparisons using a modified Bonferroni technique.
      • Hochberg Y.
      A sharper Bonferroni procedure for multiple tests of significance.
      All analyses were performed using SAS Version 9.1 (SAS Institute, Cary, NC).

      Results

      Screening, Eligibility, and Enrollment

      Fig. 1 summarizes the participant flow in terms of screening, eligibility, and enrollment. Of 4465 screening questionnaires received from the oncology clinics, nearly half (n=2185; 48.9%) were positive for pain and/or depression. This represented 1851 unique patients who screened positive for depression and/or pain because 334 patients had screened positive on more than one occasion. We were able to contact and complete eligibility interviews in 1261 screen-positive patients. We enrolled 274 (61.7%) of the 444 patients who met all entry criteria for pain and 309 (67.2%) of the 460 patients who met entry criteria for depression. Our total enrolled sample was 405 patients, of whom 96 (23.7%) had pain only, 131 (32.3%) had depression only, and 178 (44.0%) had both pain and depression.
      Figure thumbnail gr1
      Fig. 1Flow diagram of screening and enrollment of participants in INCPAD study.

      Secondary Findings From Eligibility Interview

      Additional questions were asked of the 578 patients whose pain was possibly cancer-related to better characterize pain location, duration, and severity. The location of pain was the back in 184 (31.8%), abdomen in 94 (16.3%), shoulders in 75 (13.0%), hip in 63 (10.9%), knees in 57 (9.9%), chest in 80 (13.8%), feet in 51 (8.8%), headache in 47 (8.1%), neck in 41 (7.1%), elbows or hands in 36 (6.2%), and generalized or widespread in 23 (4.0%). Pain was present in a single site in 37.7% of patients, two sites in 36.2%, and three or more sites in 26.1%. Pain had been present for less than a month in 13%, one to three months in 24%, four to 12 months in 27%, one to five years in 29%, and more than five years in 7%. The proportion of patients rating their average pain in the past week on a 0–10 scale as 1–3 (mild), 4–6 (moderate), and 7–10 (severe) was 37.4%, 55.5%, and 7.1%, respectively. However, the proportion rating their worst pain as 6 or greater (a study entry criterion) was 444 (76.8%) of the 578 patients.
      Of the 1261 patients who screened positive for depression and/or pain and who completed an eligibility interview, the distribution of PHQ-9 depression scores was 0–4 (no to minimal depressive symptoms), 5–9 (mild), 10–14 (moderate), and ≥15 (moderately severe to severe) in 42.7%, 20.9%, 19.5%, and 16.0%, respectively. A total of 460 (36.5%) patients met the entry criteria for depression (PHQ-9 score ≥10 and either depressed mood or anhedonia).

      Characteristics of the Overall Sample

      Table 1 compares characteristics of the study participants across the three study groups. Overall, the 405 study participants had a mean age of 58.8 years, 68% were women, and 20% were minority (principally African American). The type of cancer was breast in 118 (29%) of the participants, lung in 81 (20%), gastrointestinal in 70 (17%), lymphoma or hematological in 53 (13%), genitourinary in 41 (10%), and other in 42 (10%). The phase of cancer was newly diagnosed in 150 (37%) of the participants, disease free or maintenance therapy in 172 (42%), and recurrent or progressive in 83 (21%). Medication information obtained from the oncology practice records indicated that antidepressants (excluding tricyclics) were taken by 150 (37.8%) of the study participants at baseline and opioid analgesics by 214 (54.0%).
      Table 1Baseline Characteristics of 405 Subjects by Pain and Depression Group
      Baseline CharacteristicsPain Only (n=96)Depression Only (n=131)Depression and Pain (n=178)P-value
      Mean (SD) age, year60.3 (9.7)60.3 (11.0)57.0 (11.0)0.009
      Women, n (%)66 (68.8)94 (71.8)115 (64.6)0.40
      Race, n (%)0.20
       White72 (75.0)110 (84.0)140 (78.7)
       Black22 (22.9)16 (12.2)35 (19.7)
       Other2 (2.1)5 (3.8)3 (1.7)
      Education, n (%)0.34
       Less than high school23 (24.0)24 (18.3)40 (22.5)
       High school31 (32.3)63 (48.1)66 (37.1)
       Some college or trade school29 (30.2)31 (23.7)48 (27.0)
       College graduate13 (13.5)13 (9.9)24 (13.5)
      Married, n (%)48 (50.0)67 (51.2)77 (43.3)0.24
      Employment status, n (%)<0.0001
       Employed33 (34.4)22 (16.8)26 (14.6)
       Unable to work because of health or disability27 (28.1)51 (38.9)98 (55.1)
       Retired30 (31.3)48 (36.6)39 (21.9)
       Other6 (6.3)10 (7.6)15 (8.4)
      Income level, n (%)0.018
       Comfortable31 (32.3)32 (24.4)37 (20.8)
       Just enough to make ends meet50 (52.1)60 (45.8)82 (46.1)
       Not enough to make ends meet14 (12.6)38 (29.0)59 (33.2)
      Mean (SD) no. of medical diseases1.84 (1.50)2.05 (1.44)2.22 (1.76)0.18
      Type of cancer, n (%)0.37
       Breast24 (25.0)48 (36.6)46 (25.8)
       Lung18 (18.8)28 (21.4)35 (19.7)
       Gastrointestinal16 (16.7)19 (14.5)35 (19.7)
       Lymphoma and hematological16 (16.7)13 (9.9)24 (13.5)
       Genitourinary12 (12.5)14 (10.7)15 (8.4)
       Other10 (10.4)9 (6.9)23 (12.9)
      Phase of cancer, n (%)0.32
       Newly diagnosed31 (32.3)46 (35.1)73 (41.1)
       Maintenance or disease-free40 (41.7)62 (47.3)70 (39.3)
       Recurrent or progressive25 (26.0)23 (17.6)35 (19.7)
      Major depression, n (%)0 (0.0)71 (54.2)119 (66.9)<0.0001
      Baseline medication use, n (%)
      Baseline medication data were available from the oncology medical records for 396 (97.8%) of the 405 participants, including 95 of 96 of those with pain, 126 of 131 of those with depression, and 175 of 178 of those with both pain and depression.
       Antidepressants (excluding tricyclics)24 (25.3)56 (44.4)70 (40.0)0.01
       Tricyclic antidepressants4 (4.2)13 (10.3)18 (10.3)0.19
       Psychotropics (excluding antidepressants)26 (27.4)38 (30.2)51 (29.1)0.90
       Opioid analgesics51 (53.7)55 (43.7)108 (61.7)0.008
       Nonopioid analgesics43 (45.3)61 (48.4)74 (42.3)0.57
      Mean (SD) scale scores
       BPI pain severity (score range 0–10)4.85 (2.03)2.28 (2.10)5.41 (1.67)<0.0001
       SCL-20 depression (score range 0–4)0.82 (.56)1.51 (.58)1.73 (.66)<0.0001
      Mean SF functional status (score range 0–100)
       General health perceptions36.2 (29.0)32.4 (30.6)20.8 (24.8)<0.0001
       Vitality41.5 (20.5)26.5 (17.9)22.4 (15.8)<0.0001
       Mental Health74.3 (17.2)50.5 (18.6)49.9 (20.6)<0.0001
       Bodily Pain39.2 (19.8)50.6 (25.1)27.7 (15.2)<0.0001
       PCS32.8 (9.5)35.9 (8.5)30.2 (7.9)<0.0001
       MCS50.3 (10.4)37.5 (11.7)37.4 (11.2)<0.0001
      Mean Sheehan Disability (score range 0–10)3.7 (2.9)5.5 (2.7)6.4 (2.5)<0.0001
      Mean overall quality of life (score range 0–10)7.1 (2.2)5.2 (1.8)5.2 (2.3)<0.0001
      Mean GAD-7 anxiety (score range 0–21)3.7 (3.9)8.2 (5.5)9.9 (5.9)<0.0001
      Mean disability days in past four weeks
       Bed days2.7 (5.0)5.0 (7.2)7.7 (8.5)<0.0001
       Days activities reduced by ≥50%9.5 (9.7)11.5 (9.0)11.9 (8.5)0.096
       Total disability days12.2 (10.4)16.5 (10.2)19.6 (9.2)<0.0001
      SD = standard deviation.
      a Baseline medication data were available from the oncology medical records for 396 (97.8%) of the 405 participants, including 95 of 96 of those with pain, 126 of 131 of those with depression, and 175 of 178 of those with both pain and depression.
      The 405 study participants reported an average of 16.8 of the past 28 days (i.e., 60% of their days in the past four weeks) in which they were either confined to bed (5.6 days) or had to reduce their usual activities by 50% (11.2 days) because of pain or depression. Moreover, 176 (43%) reported being unable to work because of health-related reasons. The mean SF-12 PCS score of 32.7 substantiates the rather severe degree of impairment, as does the mean SF-36 Vitality (28.3) and General Health Perceptions (28.2) scores.

      Symptom Severity and HRQL

      The average SCL-20 depression score in the 309 depressed participants was 1.64 (on a 0–4 scale), and the average BPI severity score in the 274 participants with pain was 5.2 (on a 0–10 scale), representing at least moderate levels of symptom severity. As expected, the pain-specific (BPI severity and SF bodily pain) scores were higher in the pain only and depression and pain groups, whereas the depression and mental health-specific (SCL-20, GAD anxiety, and SF MCS) scores were higher in the depression only and depression and pain groups (Table 1). In terms of the three more generic HRQL measures (general health perceptions, vitality scores, and overall quality of life), the depression-only group tended to have worse scores than the pain-only group, with the worst scores seen in the group with comorbid pain and depression.

      Disability

      There was an incremental increase in total disability days in the past four weeks as one went from the pain only (12.2 days) to depression only (16.5 days) to comorbid pain and depression (19.6 days) subgroups. Likewise, the proportion of patients being unable to work because of health-related reasons progressively increased among these three groups (28% vs. 39% vs. 55%), as did the Sheehan Disability Index (3.7 vs. 5.5 vs. 6.4).

      Self-Reported Treatments for Pain and Depression

      Table 2 summarizes the treatments that patients reported taking for their pain and depression. Only a minority of patients reported receiving current care from a mental health professional or taking St. John's Wort or other herbal treatments. Most patients were taking a medication for their pain, whereas few reported nonpharmacological treatments. Of the 258 subjects enrolled in the study for pain who provided information on hours of relief from their pain medication, more than one-third (n=95; 36.8%) reported three hours or less of relief. Patients in the pain-only group reported that pain medications relieved 69.8% of their pain, whereas patients in the pain and depression group reported 63.4% relief. Although many patients with pain reported seeing a variety of specialists sometime in their lifetime for pain, few were currently going to a pain clinic (6.9% of those enrolled for pain) or receiving physical therapy, chiropractic care, massage therapy, or acupuncture. Consulting other specialists for pain was only asked in terms of lifetime use, and here, the most commonly seen were orthopedics and neurology.
      Table 2Depression and Pain-Specific Treatments Reported by Study Subjects
      TreatmentPain Only (n=96)Depression Only (n=131)Pain and Depression (n=178)
      Depression treatmentsN (%)
       St. John's Wort or other herbals
      Ever9 (9.4)23 (17.6)25 (14.0)
       Mental health professional
      Ever39 (40.6)47 (35.9)83 (46.6)
      Current4 (4.2)16 (12.2)24 (13.5)
      Pain treatmentsn (%)
      Pain treatments (can include more than 1)
       Over-the-counter medications35 (36.5)31 (23.7)61 (34.3)
       Prescribed medications71 (74.0)59 (45.0)151 (84.8)
       Nonpharmacological treatments0 (0.0)0 (0.0)1 (0.6)
       No pain treatments3 (3.2)58 (44.3)4 (2.3)
      Hours of relief from pain medicines (of 329 with analyzable data)(n=90)(n=71)(n=168)
       0–15 (5.6)10 (14.1)16 (9.5)
       2–317 (18.9)7 (9.9)47 (28.0)
       426 (28.9)15 (21.1)37 (22.0)
       5–1236 (40.0)26 (36.6)58 (34.5)
       >126 (6.7)13 (18.3)10 (6.0)
      Specialists seen specifically for pain, and when
       Pain clinic
      Ever20 (20.8)17 (13.0)35 (19.7)
      Current5 (5.2)4 (3.1)12 (6.7)
       Physical therapy
      Ever46 (47.9)65 (49.6)98 (55.1)
      Current7 (7.3)3 (2.3)15 (8.4)
       Chiropractor
      Ever40 (41.7)58 (44.3)68 (38.2)
      Current2 (2.1)3 (2.3)5 (2.8)
       Massage therapy
      Ever24 (25.0)17 (13.0)43 (24.2)
      Current4 (4.2)1 (0.8)12 (6.7)
       Acupuncture
      Ever6 (6.3)7 (5.3)9 (5.1)
      Current1 (1.0)1 (0.8)0 (0.0)
       Orthopedic surgeon
      Ever32 (33.3)47 (35.9)72 (40.5)
       Neurologist
      Ever28 (29.2)30 (22.9)58 (32.6)
       Rheumatologist
      Ever13 (13.5)12 (9.2)31 (17.4)
       Another specialist for pain
      Ever5 (5.2)13 (9.9)25 (14.0)
       Nonpharmacological treatments
      Ever9 (9.4)14 (10.7)18 (10.1)

      Association of Depression and Pain with HRQL and Disability

      As noted previously, multivariable regression models were run in four steps for the each of the three generic HRQL outcomes and two disability measures. Table 3 shows the results of these four models for each dependent variable. In the final models, which included both pain and depression as well as covariates and were adjusted for multiple comparisons, depression had a strong association (P<0.0001) with all five measures, whereas pain had a weaker but significant association with three measures: SF general health perceptions (P=0.049), overall quality of life (P=0.048), and total disability days in the past four weeks (P=0.049).
      Table 3Association of Depression and Pain with HRQL and Disability: Results from Multivariable Regression Models
      HRQL or Disability Domain
      Generalized linear regression (GLM) modeling was conducted for the two SF domains, Sheehan Disability Index, and quality of life. Poisson regression modeling was conducted for total disability days. Standardized beta is beta coefficient from regression model divided by its standard error and is value reported for GLM models. Chi-square is reported for Poisson models (which is only for total disability days).
      Strength of Association of Depression (HSCL-20) and Pain (BPI) Severity with HRQL/Disability
      Association of each HRQL or disability domain with depression and pain was examined in multivariable models in four steps: association with depression alone (Step 1) and pain alone (Step 2) in separate models, with depression and pain together in combined model (Step 3), and with depression and pain adjusted for covariates of age, sex, race, medical comorbidity, education, income, and employment status (Step 4).
      Separate Models for Depression and Pain (Steps 1 and 2)Combined Model with Both Depression and Pain (Step 3)Combined Model Adjusted for Covariates (Step 4)
      Standardized Beta or Chi-SquareP-valueStandardized Beta or Chi-SquareP-valueStandardized Beta or Chi-SquareP-value
      Adjusted for multiple comparisons using modified Bonferroni procedure.
      SF General Health Perceptions
       Depression−5.45<0.0001−5.04<0.0001−3.97<0.0001
       Pain−3.820.0002−3.230.0013−2.410.049
      SF Vitality
       Depression−14.29<0.0001−14.22<0.0001−14.27<0.0001
       Pain−1.120.270.520.61−0.430.67
      Quality of life, overall
       Depression−10.21<0.0001−10.53<0.0001−9.58<0.0001
       Pain1.030.302.540.0122.610.048
      Sheehan Disability Index
       Depression12.76<0.000112.42<0.000111.29<0.0001
       Pain3.350.00092.260.0241.820.14
      Total disability days in past four weeks
       Depression433.0<0.0001404.3<0.0001302.1<0.0001
       Pain37.0<0.000110.30.00136.30.049
      a Association of each HRQL or disability domain with depression and pain was examined in multivariable models in four steps: association with depression alone (Step 1) and pain alone (Step 2) in separate models, with depression and pain together in combined model (Step 3), and with depression and pain adjusted for covariates of age, sex, race, medical comorbidity, education, income, and employment status (Step 4).
      b Generalized linear regression (GLM) modeling was conducted for the two SF domains, Sheehan Disability Index, and quality of life. Poisson regression modeling was conducted for total disability days. Standardized beta is beta coefficient from regression model divided by its standard error and is value reported for GLM models. Chi-square is reported for Poisson models (which is only for total disability days).
      c Adjusted for multiple comparisons using modified Bonferroni procedure.

      Self-Reported Health Care Use

      Health care use in the preceding three months is summarized in Table 4. Although it was not surprising that nearly all patients had outpatient visits, the sheer volume of visits was impressive, with 31.6% of the patients having three to five outpatient visits, 28.4% having six to 10 visits, and 25.6% having more than 10 visits. In terms of more costly resources, 38% of patients reported at least one hospitalization in the past three months, with the total hospital days being one to two days in 8.7% of the study sample, three to five days in 9.7%, six to 10 days in 11.6%, and more than 10 days in 7.9%. One-third (33.1%) of the study patients reported at least one ED visit, with one of six (16.8%) reporting multiple ED visits. In contrast, a minority (17.8%) of patients reported any mental health visits during the preceding three months (defined as “psychiatrists, psychologists, social workers, psychiatric nurses, or counselors”). Even among the 309 patients with depression, less than one in five (n=61, 19.7%) had seen a mental health professional. Finally, visits to CAM providers (defined as “alternative health care providers such as chiropractors, acupuncturists, massage therapists, or others”) were rare (only 4.7% of patients). There were no significant differences among the three symptom subgroups in their use of any of the categories of health care services.
      Table 4Patient-Reported Health Care Use in the Past Three Months in INCPAD Participants by Pain and Depression Subgroup
      There were no significant differences among the three symptom groups for any of the five measures of health care use, either in unadjusted analyses or in analyses adjusted for multiple comparisons using a modified Bonferroni procedure.
      Number of Visits or Days
      0123–56–10>10
      Health Care Use Variablen(%)n(%)n(%)n(%)n(%)n(%)
      Outpatient visits (n=402)22433127114103
       Pain only (n=95)0(0.0)9(9.5)10(10.5)33(34.7)26(27.4)17(17.9)
       Depression only (n=131)1(0.8)4(3.1)13(9.9)39(29.8)36(27.5)38(29.0)
       Pain and depression (n=176)1(0.6)11(6.3)9(5.1)55(31.3)52(29.5)48(27.3)
      Hospital days (n=404)2512411394732
       Pain only (n=96)62(64.6)4(4.2)4(4.2)10(10.4)9(9.4)7(7.3)
       Depression only (n=131)82(62.6)5(3.8)2(1.5)14(10.7)15(12.2)13(9.9)
       Pain and depression (n=177)107(60.5)15(8.5)5(2.8)15(8.5)23(13.0)12(6.8)
      ED visits (n=405)27166313070
       Pain only (n=96)73(76.0)11(11.5)4(4.2)7(7.3)1(1.0)0(0.0)
       Depression only (n=131)95(72.5)18(13.7)10(7.6)6(4.6)2(1.5)0(0.0)
       Pain and depression (n=178)103(57.9)37(20.8)17(9.6)17(9.6)4(2.2)0(0.0)
      Mental health visits (n=405)33325211286
       Pain only (n=96)85(88.5)2(2.1)6(6.3)2(2.1)1(1.0)0(0.0)
       Depression only (n=131)109(83.2)10(7.6)7(5.3)3(2.3)1(0.8)1(0.8)
       Pain and depression (n=178)139(78.1)13(7.3)8(4.5)7(3.9)6(3.4)5(2.8)
      CAM visits (n=405)38633742
       Pain only (n=96)92(95.8)0(0.0)2(2.1)2(2.1)0(0.0)0(0.0)
       Depression only (n=131)127(96.9)1(0.8)0(0.0)1(0.8)2(1.5)0(0.0)
       Pain and depression (n=178)167(93.8)2(1.1)1(0.6)4(2.2)2(1.1)2(1.1)
      a There were no significant differences among the three symptom groups for any of the five measures of health care use, either in unadjusted analyses or in analyses adjusted for multiple comparisons using a modified Bonferroni procedure.

      Discussion

      Our study has several important findings. First, of more than 4400 questionnaires administered to patients in 16 oncology practice sites, nearly half screened positive for pain and/or depression of at least moderate severity, confirming the high prevalence of these two symptoms in cancer populations.
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      Second, pain and depression frequently co-occur and are synergistic in their association with impairment; 44% of our sample had comorbid depression and pain, and this subgroup had the worst quality of life and disability. The high comorbidity of pain and depression and their reciprocal adverse effects on one another and on quality of life and functioning has been reported for cancer
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      Third, our sample experienced marked disability both in terms of profound activity limitations (i.e., an average of 60% of days in the past four weeks spent either in bed or with activities reduced by at least 50%) and 43% reporting unemployment because of health reasons. Fourth, our sample had substantial health care use, but a low use of specialty care for depression and pain, meaning that the oncologist and/or patient's primary care physician are the de facto principal provider of symptom-based care for cancer patients.
      The distribution of cancer type and phase was similar among our three patient groups (i.e., pain only, depression only, and comorbid pain and depression). Previous research has shown that depression and other psychological symptoms are prevalent regardless of site of cancer
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      Likewise, pain was distributed across the spectrum of cancer phases from newly diagnosed to maintenance or disease free to recurrent or progressive. Thus, general screening for pain and depression in oncology practice is probably warranted rather than a narrow focus on certain subgroups of cancer patients.
      The first step to better management of cancer-related symptoms is increased detection. The depression screener used in our study was the PHQ-2, which screens for the two core symptoms of depressive disorders, that is, depressed mood and anhedonia.
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      Ultrabrief screeners have been validated for depression in general,
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      including in cancer patients.
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      Also, ultrabrief screeners ranging from one to three items are validated for pain.
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      However, patients and physicians often expect the other party to initiate discussions about symptoms and quality-of-life issues.
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      Therefore, educating physicians to ask about pain, depression, and other cancer symptoms and coaching and empowering patients to report such symptoms are essential.
      Depression and pain had moderate to strong associations with impairment across multiple domains of quality of life and functional status. Depression tended to have somewhat stronger effects than pain, and depression-pain comorbidity yielded the greatest impairment. The relationship between symptom burden and quality of life in cancer patients has been noted,
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      The frequent co-occurrence of pain and depression (45% in our sample) and their additive adverse effects make them an especially pernicious symptom dyad.
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      Beyond a simple decrement in quality of life and functional status, our study demonstrated a considerable degree of frank disability. Patients reported more than 60% of their days in bed or with marked reductions in activity and a 43% health-related unemployment rate. Apart from cancer, depression and pain are two of the most common causes of decreased work productivity.
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      Health care use did not differ by symptom group in our study. The considerable amount of health care use in our study exemplifies the high financial burdens associated with cancer care, which includes not only direct medical expenses
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      The National Cancer Institute estimated that the total direct medical costs associated with cancer diagnosis and treatment in the United States in 2004 was $72.1 billion, whereas the indirect costs were even larger at $118 billion.
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      Despite high health care use by patients in our trial, their self-reported treatments suggested a rather low rate of treatments specific to depression and pain, including only a small proportion of patients accessing mental health or pain specialists and many patients reporting insufficient relief from pain medications. This suggests that oncology services may continue to focus principally on treatment of the cancer itself with much less attention paid to symptoms that accompany the cancer or its treatment. Although some patients may access CAM care, CAM was used by only a fraction of our patients and nationally accounts for only a small percent of cancer expenditures.
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      improving clinician knowledge and attitudes,
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      addressing patient and clinician misconceptions about cancer pain and its treatment,
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      Among psychotherapeutic interventions, cognitive-behavioral therapy
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      seem particularly promising. Given the context and competing demands of busy oncology practices, collaborative care interventions, which have consistently proven effective for depression in general medical settings,
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      might be an efficient strategy for cancer-related symptom management. Indeed, a collaborative telecare management approach covering multiple oncology practices is the focus of our present trial.
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      Our study has several limitations. The cross-sectional nature of our data prevents us from establishing a causal effect of depression and pain on the substantial functional impairment, decreased quality of life, and high health care use found in our study participants. However, there is considerable evidence that depression and pain individually do worsen these health outcomes, and that in combination have additive ill effects.
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      • Kroenke K.
      Depression and pain comorbidity: a literature review.
      Second, INCPAD enrolled a broad range of patients both by type and phase of cancer. This is a study strength in terms of generalizability to oncology practice but limits our ability to draw definitive conclusions about depression and pain in any one type or phase of cancer. Third, most data were obtained by patient self-report, which is the criterion standard for symptoms, such as depression and pain, and functional status and quality of life domains, but may be less desirable for health care use. The latter is available from automated records in large integrated health care systems but is not feasibly obtained in a statewide trial such as INCPAD that involves individual rural and urban community-based oncology practices. Self-report correlates reasonably well with actual health care use
      • Cleary P.D.
      • Jette A.M.
      The validity of self-reported physician utilization measures.
      and has been relied on in previous community-based depression trials.
      • Rost K.
      • Pyne J.M.
      • Dickinson L.M.
      • LoSasso A.T.
      Cost-effectiveness of enhancing primary care depression management on an ongoing basis.
      Although it may introduce some measurement imprecision into absolute rates of health care use, it is less likely to bias between-group comparisons.
      In summary, depression and pain are prevalent across a wide range of cancer types and phases and are associated with increased disability and diminished HRQL. Compared with pain, depression tends to have a somewhat greater and more pervasive effect across multiple domains. This may be because of a number of factors ranging from depression being especially impairing to it being less readily recognized or treated by oncologists to greater reluctance by patients to accept a depression diagnosis or treatment. The frequent co-occurrence of depression and pain, as well as their additive effects in several domains, suggests that the detection of one symptom should trigger inquiry about the other. Our INCPAD trial will address the degree to which impairment is reduced by the comanagement of pain and depression.

      Acknowledgments

      The authors gratefully acknowledge the care management provided by Becky Sanders and Susan Schlundt, the project coordination by Kelli Norton, and the research assistance of Stephanie McCalley and Pam Harvey.

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