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Original Investigation |

Somatic Symptoms in Patients With Cancer Experiencing Pain or Depression:  Prevalence, Disability, and Health Care Use FREE

Kurt Kroenke, MD; Xin Zhong, RN; Dale Theobald, MD, PhD; Jingwei Wu, MS; Wanzhu Tu, PhD; Janet S. Carpenter, PhD, RN
[+] Author Affiliations

Author Affiliations: Center for Implementing Evidence-Based Practice, Richard Roudebush VA Medical Center, Indianapolis (Dr Kroenke); Department of Medicine (Drs Kroenke and Tu and Mr Wu) and School of Nursing (Ms Zhong and Dr Carpenter), Indiana University, Indianapolis; Regenstrief Institute Inc, Indianapolis (Drs Kroenke and Tu); and Community Home Health Hospice and Symptom Management Group, Indianapolis (Dr Theobald).


Arch Intern Med. 2010;170(18):1686-1694. doi:10.1001/archinternmed.2010.337.
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Published online

Background  The adverse impact of a high somatic symptom burden is well established for primary care and other noncancer populations with chronic medical disorders.

Methods  This study examines the impact of somatic symptom burden on disability and health care use in patients with cancer experiencing pain, depression, or both. We performed secondary analyses of baseline data from 405 patients with cancer enrolled in a telecare management trial for pain or depression. Somatic symptom burden was measured using a 22-item scale. Multivariable models were conducted to determine the association of somatic symptom burden with the Sheehan Disability Scale (SDS) score, the number of self-reported disability days in the past 3 months, and health care use. Models were adjusted for sociodemographic characteristics, medical comorbidity, and depression and pain severity.

Results  Somatic symptoms were highly prevalent, with 15 of the 22 symptoms reported by more than 50% of patients. The somatic symptom burden was similar across different types and phases of cancer. The mean SDS score (scored 0-10 [not at all disabled to unable to carry out any activities]) was 5.4, and the mean number of self-reported disability days in the past 4 weeks was 16.9. In multivariable models, somatic symptom burden was associated with SDS score (P < .001) and the likelihood of at least 14 disability days in the past 4 weeks (odds ratio, 1.51; 95% confidence interval, 1.19-1.92) but not with increased health care use.

Conclusions  The somatic symptom burden is high in patients with cancer who experience pain or depression. Given the strong association with disability and the high prevalence of many types of symptoms, recognizing and managing somatic symptoms may be important in improving quality of life and functional status regardless of type or phase of cancer.

Trial Registration  clinicaltrials.gov Identifier: NCT00313573

Somatic symptoms have been the subject of numerous studies1,2 in the general population and in primary care and specialty clinic settings. Somatic symptoms account for more than half of all general medical visits, lack a definitive medical explanation one-third to half of the time, and are frequently persistent. Physical and psychological factors seem to contribute to somatic symptom reporting, even in patients with chronic medical disorders.3,4 These symptoms are associated with substantial functional impairment, disability, and health care use, even after controlling for medical and psychiatric comorbidity.57

Studies818 of symptom prevalence in cancer have often focused on patients with advanced cancer or with selected types of cancer seen at tertiary care centers. A literature synthesis of 44 studies involving more than 25 000 patients17 showed that symptoms manifest in at least 30% of patients with cancer include fatigue (74%), pain (71%), weakness (60%), appetite loss (53%), dry mouth (40%), depressed mood (39%), constipation (37%), insomnia (36%), dyspnea (35%), nausea (31%), and anxiety (30%). Somatic symptoms can have a substantial effect on functional status, quality of life, and even the desire for a hastened death.14,1924 Somatization (the relationship between psychological distress and somatic symptom reporting) has been the focus of only a few small cancer studies.2529 This is an important gap given that numerous studies2,4,30 in noncancer medical populations demonstrate a high prevalence of poorly or partially explained symptoms, even among symptoms considered to be more disease specific.

The purpose of this study was to examine somatic symptom prevalence, disability, and health care use in patients with cancer using baseline data from the Indiana Cancer Pain and Depression (INCPAD) trial. In contrast to previous studies, the INCPAD trial drew participants from multiple community-based oncology practices and included a wide range of types and phases of cancer. Although all INCPAD patients had pain, depression, or both, standardized assessment of pain, anxiety, depression, and medical comorbidity facilitated adjustment for these potential confounders. Hypotheses for the secondary analyses in this article are as follows: (1) Somatic symptoms are prevalent in patients with cancer who present with pain, depression, or both. (2) The somatic symptom burden in patients with cancer is associated with greater disability, even after controlling for pain, anxiety, depression, and other relevant covariates. (3) The somatic symptom burden in patients with cancer is associated with greater health care use, even after controlling for pain, anxiety, depression, and other relevant covariates.

SETTING AND SAMPLE

The present study uses baseline data from patients enrolled in the INCPAD trial, which is described in detail elsewhere.31 Briefly, participants were recruited from 16 oncology outpatient sites throughout urban and rural areas of Indiana to test the effectiveness of telecare management vs usual care for the treatment of depression or cancer-related pain. Between March 1, 2006, and August 31, 2008, patients presenting to the oncology practices on selected days were screened for INCPAD study inclusion. Patients were potentially eligible if they had depression or pain of at least moderate severity (ie, a Patient Health Questionnaire [PHQ] 8-item depression scale score of ≥1032,33 or worst pain in the past week of ≥6 on a 0-10 [none to severe] scale31). In addition, pain had to be cancer related and persistent despite the use of at least 1 analgesic.

Patients were excluded if they (1) did not speak English, (2) had moderately severe cognitive impairment, (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 adverse effect (eg, interferon or corticosteroids) and in whom short treatment duration and tolerable depression severity justify withholding antidepressant therapy, (6) were pregnant, or (7) were in hospice care.

MEASURES

The primary independent variable is the number and severity of somatic symptoms as measured using a 22-item somatic symptom burden scale. This scale consists of 14 symptoms from the PHQ-15 somatic scale (all items except sexual dysfunction)34 plus 8 symptoms from the Memorial Symptom Assessment Scale35 and the M.D. Anderson Symptom Inventory.15 The PHQ-15 and the M.D. Anderson Symptom Inventory have been shown to have good internal reliability (Cronbach α = .80 and .82, respectively), as did the composite 22-item scale used in this study (Cronbach α = .76). Respondents are asked to rate on a scale from 0 to 2 the degree to which each symptom has bothered them in the past 4 weeks (from “not bothered at all” to “bothered a little” to “bothered a lot”). Increasing scores on this 0- to 44-point scale can reflect a greater number or greater severity of symptoms; thus, higher scores reflect a greater somatic symptom burden.

The dependent variables are disability and health care use. Disability was assessed using 2 measures. One was the 3-item Sheehan Disability Scale (SDS), which asks respondents to what extent on a scale from 0 to 10 their health has interfered with their work, family life, and social life in the past month.36 The SDS score is the mean of the 3 items, and higher scores reflect greater disability. Previous research has shown high correlations among the 3 items of the SDS, resulting in strong internal reliability consistency in previous research (Cronbach α = .89)37,38 and in our own sample (α = .82), as well as good construct validity and responsiveness.39 A second measure was the number of days in the past 4 weeks that respondents reported they either had to stay in bed or reduce their usual activities by at least 50% due to physical health or emotional problems.40 Health care use was assessed by asking study participants about their use of 5 types of health care in the 90 days preceding study enrollment: outpatient visits, hospital days, emergency department (ED) visits, mental health visits, and visits to a complementary and alternative medicine provider.

The principal covariates were pain and depression. Pain severity was measured using the 4-item Brief Pain Inventory (BPI) severity scale (Cronbach α = .79).41,42 Respondents rated their average, worst, least, and current pain in the past week on a scale from 0 (“no pain”) to 10 (“pain as bad as you can imagine”), and the mean of the 4 items was determined, with higher scores reflecting more severe pain. Depression severity was assessed using the 20-item Hopkins Symptom Checklist (HSCL-20) depression scale (α = .89).42,43 Respondents rated how much they were distressed in the past month by each of the items on a scale from 0 (“not at all”) to 4 (“extremely”), and the mean of the 20 items was determined, with higher scores reflecting more severe depression.

Several additional covariates were used in the analyses. Anxiety was assessed using the 7-item Generalized Anxiety Disorder (GAD-7) scale (α = .86), a validated scale that assesses anxiety severity and the likelihood of the 4 most common clinical anxiety disorders: generalized anxiety disorder, panic disorder, social anxiety disorder, and posttraumatic stress disorder.44 Respondents are asked to indicate how often in the past 2 weeks they had been bothered by each symptom on a scale from 0 (“not at all”) to 3 (“nearly every day”). The individual GAD-7 item scores are summed, and higher scores on this 0 to 21 scale indicate greater anxiety. Medical comorbidity was assessed using a checklist of 8 common categories of medical disorders: heart disease, pulmonary disease, diabetes mellitus, hypertension, neurologic conditions, arthritis, liver disease, and renal disease.45 Sociodemographic variables included age, sex, race, education, employment, and income. The socioeconomic disadvantage index assigns 1 point each for low education (less than high school), unemployment, and low income (“not enough to make ends meet”).46 Higher scores on this 0 to 3 scale represent worse socioeconomic conditions. Cancer type and phase were abstracted from oncology records. Cancer phase was categorized as newly diagnosed, maintenance therapy only, disease free, recurrent cancer, and progressive cancer.

STATISTICAL ANALYSIS

Scoring of the somatic symptom burden scale was described in the “Measures” subsection. The other measures (PHQ-8, SDS, BPI, HSCL-20, GAD-7, and disability days) were scored by algorithms recommended by the developers. Because items were infrequently missing (<5% on all scales), a missing item was assigned a score of 0. Also, because this article used baseline data obtained by direct interview of all 405 participants, all bivariate analyses and multivariable models included data from 403 to 405 participants.

For hypothesis 1, we reported prevalence rates (including 95% confidence intervals [CIs]) for each of the 22 somatic symptoms. We also assessed bivariate associations of the somatic symptom burden score with sociodemographic characteristics, type and phase of cancer, depression, anxiety, and measures of disability and health care use to identify potential confounders and adjust for them in multivariable models (hypotheses 2 and 3). Variables that were significant in bivariate relationships at P > .20 were not entered into subsequent multivariable modeling.

For hypothesis 2, multiple linear regression analysis was used to assess associations of somatic symptom burden, pain, depression, and other covariates with the SDS score. Similarly, we used logistic regression analysis to assess associations of these variables with the number of self-reported disability days. Herein, disability days were dichotomized as 14 days or more (coded as 1) vs less than 14 days (coded as 0) in the past 4 weeks. For hypothesis 3, multivariable logistic regression models were used to evaluate associations of somatic symptom burden, pain, depression, and other covariates with ED visits (any vs none) and mental health care visits (any vs none).

For the 5 continuous variables in the final models, we report variable estimates or odds ratios (ORs) in terms of meaningful units of change, including 10 years for age, 0.5 U for HSCL-20 depression score (possible range, 0-4), 1 U for BPI pain severity score (possible range, 0-10), 5 U for GAD-7 anxiety score (possible range, 0-21), and 5 U for somatic symptom score (possible range, 0-44). The unit changes used for the 4 scale scores were derived from previous research.34,42,44,47 Data analysis was implemented using a software program (SAS version 9.1.2; SAS Institute Inc, Cary, North Carolina).

STUDY SAMPLE

The 405 study participants had a mean age of 58.8 years (age range, 23-96 years); 79.5% were white, 67.9% were women, and 49.1% were married. The mean number of comorbid medical diseases was 2.1. Educational level varied, with 21.5% having less than a high school education, 39.5% having only a high school education, and 39.0% having college credits or a college degree. The most frequently reported employment status was being unable to work due to disability (43.6%), followed by retired (29.0%), employed (20.0%), and other (7.4%). Income was reported as making just enough to make ends meet (47.6%), not comfortable (27.5%), or being comfortable (24.8%). There were 96 participants (23.7%) with pain only, 131 (32.3%) with depression only, and 178 (44.0%) with pain and depression. For the total sample, the mean HSCL-20 depression severity score (possible range, 0-4 [least to worst]) was 1.5, and the mean BPI pain severity score (possible range, 0-10 [least to worst]) was 4.7, both representing mild to moderate levels of symptom severity.42 The type of cancer was breast in 118 participants (29.1%), lung in 81 (20.0%), gastrointestinal in 70 (17.3%), lymphoma or hematologic in 53 (13.1%), genitourinary in 41 (10.1%), and other in 42 (10.4%). The phase of cancer was new onset in 150 (37.0%), maintenance or disease free in 172 (42.5%), and recurrent or progressive in 83 (20.5%).

Participants had a mean (SD) somatic symptom burden score (possible range, 0-44 [least to worst]) of 18.3 (6.6), with a median of 18, an interquartile range (25th-75th percentile) of 14 to 23, and a 90% percentile score of 27. They had a mean (SD) PHQ-14 subscale score (possible range, 0-28 [least to worst]) of 12.2 (4.3), with a median of 12, an interquartile range of 9 to 15, and a 90th percentile score of 18. These PHQ-14 scores are indicative of a moderate somatic symptom burden in noncancer medical populations.34

The mean SDS score (possible range, 0-10 [least to worst]) was 5.4, and the mean number of self-reported disability days in the past 4 weeks was 16.9, including 5.7 bed days and 11.2 days where there was a 50% or greater reduction in usual activities. Thus, participants reported 60% of their past 28 days as full or partial disability days. The number of participants who reported 14 or more disability days in the past 4 weeks was 238 (58.8%).

Self-reported health care use in the 3 months preceding study enrollment was high. The proportion of patients who reported 3 to 5, 6 to 10, and more than 10 outpatient visits was 32%, 28%, and 26%, respectively. More than one-third of the patients (38%) reported at least 1 hospitalization, and the proportion of the entire sample reporting 3 to 5, 6 to 10, and more than 10 hospital days was 10%, 12%, and 8%, respectively. An ED visit was reported by 33% of the patients (n = 134), with 17% reporting 2 or more ED visits. A mental health visit was reported by 18% of the patients (n = 72), with 12% reporting 2 more such visits. Finally, few patients (4.7%) reported any visits to a complementary and alternative medicine provider.

PREVALENCE OF INDIVIDUAL SOMATIC SYMPTOMS

Somatic symptoms were prevalent in all patients with cancer presenting with pain, depression, or both (Table 1). Almost all the patients reported feeling tired (97.5%), and most were bothered a lot by this symptom (78.8%). The 5 most commonly reported symptoms were feeling tired (fatigue), difficulty sleeping, pain in the limbs or joints, back pain, and difficulty remembering things. Of the 22 symptoms inquired about, 15 were reported by more than 50% of patients, and 14 were reported as very bothersome by at least 20% of patients. We also examined the proportion of patients reporting a symptom as very bothersome (ie, they felt that they were “bothered a lot” by the symptom). For example, 319 of the 395 individuals (80.8%) reporting fatigue felt that they were bothered a lot by fatigue, whereas only 82 (35.8%) of the 229 individuals reporting headaches were bothered a lot by their headaches. Excluding the 2 symptoms infrequently endorsed (menstrual problems and fainting spells), patients were most likely to rate fatigue, sleep complaints, pain in the limbs or back, and dry mouth as very bothersome (>60% of patients reporting these symptoms felt that they were bothered a lot) and least likely to rate headaches, dizziness, nausea, vomiting, palpitations and chest pain as very bothersome (<40% of patients reporting these symptoms felt that they were bothered a lot).

Table Graphic Jump LocationTable 1. Somatic Symptom Prevalence and Severity in 405 Patients With Cancer and Comorbid Pain, Depression, or Both
BIVARIATE CORRELATES OF SOMATIC SYMPTOM BURDEN

The somatic symptom burden was associated with education, employment status, income, and an ED or mental health visit in the past 3 months but not with sex, race, or marital status (Table 2). Regarding continuous variables, the somatic symptom burden was strongly correlated with HSCL-20 depression severity (0.61) and GAD-7 anxiety severity (0.50), moderately correlated with the SDS score (0.45) and self-reported disability days (0.38), and weakly correlated with medical comorbidity (0.22) and age (−0.17). All these correlations were significant at P < .001. Somatic symptom burden was not significantly correlated with either outpatient visits (0.05) or hospital days (0.06) in the past 3 months.

Table Graphic Jump LocationTable 2. Bivariate Associations of Somatic Symptom Burden Score With Sociodemographic Characteristics and Health Care Use

Mean (SD) somatic symptom burden scores by cancer type and phase are given in Table 3. There were no significant differences by cancer type (P = .22) or cancer phase (P = .28), indicating a similar somatic symptom burden across different types and phases of cancer.

Table Graphic Jump LocationTable 3. Mean (SD) Somatic Symptom Burden Scores by Type and Phase of Cancer
SOMATIC SYMPTOM BURDEN AND DISABILITY

Table 4 provides multivariable regression results for disability. For every 5-U increase in somatic symptom burden, the SDS score increased (worsened) by 0.42 points. Depression was the only other significant predictor: for every 0.5-U increase in depression (on the 0 to 4 HSCL-20 scale), the SDS score increased (worsened) by 0.90 points. These changes in SDS score (which has an SD of 2.86) associated with somatic symptom burden and depression in the multivariable model are equivalent to effect sizes (ie, change divided by the SD) of 0.15 and 0.31, respectively. Effect sizes of 0.2 and 0.5 are commonly considered small and moderate changes in health status.48 An effect size of 0.2 would correspond to an SDS change of 0.75, which, in turn, would be approximately a 9-point change on the somatic symptom burden scale.

Table Graphic Jump LocationTable 4. Multivariable Correlates of Disability in Patients With Cancer and Comorbid Pain, Depression, or Botha

Disability days were also independently associated with somatic symptom burden and depression. For every 5-U increase in somatic symptom burden, the probability of having at least 14 disability days in the past 28 days increased by 50% (OR, 1.51; 95% CI, 1.19-1.92). The only other significant variable was depression: for every 0.5-U increase in HSCL-20 depression scores, the probability of having at least 14 disability days increased by 60% (OR, 1.60; 95% CI, 1.24-2.07).

SOMATIC SYMPTOM BURDEN AND HEALTH CARE USE

Because bivariate analyses showed no association of somatic symptom burden with outpatient visits or hospital days, multivariable modeling was conducted only for ED and mental health visits (too few patients reported complementary and alternative medicine visits to model this variable). One or more ED visits in the past 3 months were reported by 134 participants (33.1%), and 1 or more mental health visits were reported by 72 (17.8%). Multivariable logistic regression models entering the same independent variables given in Table 4 showed that only greater socioeconomic disadvantage was associated with a higher likelihood of ED visits (OR, 1.55; 95% CI, 1.20-1.99) and that only race (black/other vs white: 1.90; 1.01-3.60) and not being married (1.81; 1.03-3.20) were associated with a higher likelihood of mental health visits. Somatic symptom burden was not associated with a higher likelihood of having an ED visit (OR, 1.20 for each 5-point increase in somatic symptom score; 95% CI, 0.97-1.49; P = .10) or a mental health visit (1.24 for each 5-point increase; 0.96-1.61; P = .10). Likewise, neither depression nor pain severity was associated with either ED or mental health visits.

The present study has several important findings. Numerous somatic symptoms (rather than just a few) are highly prevalent in patients with cancer and comorbid pain depression or both. Moreover, somatic symptom burden seems similar across a range of cancer types and phases. Somatic symptom burden is associated with disability even after controlling for potential confounders. In contrast, somatic symptom burden is unrelated to increased health care use.

Note that all the patients in this sample had pain, depression, or both. Pain and depression are 2 of the most common and potentially treatable symptoms in patients with cancer. Pain is present in 14% to 100% of patients with cancer, depending on the setting, and the prevalence of major depressive disorder is 10% to 25%, with a similar range for clinically depressive symptoms.4952 However, the reporting of most somatic symptoms is increased in the presence of depression.53 Thus, somatic symptom burden is likely to be higher in the present study sample than in a general cancer population not selected specifically for the presence of pain or depression.

An important question is whether this study was adequately powered to detect significant associations. We examined bivariate associations between somatic symptom burden and other variables to limit the number of variables entered into the models. As a result, we modeled as dependent variables 2 measures of health care use that were associated with somatic symptom burden in bivariate analyses and 2 distinct measures of disability. Bivariate screening also limited the number of independent variables entered into the models to 10. Because approximately 10 events for each independent variable in a multivariable model are typically desired, this would correspond to 100 events for these models. Three of the 4 models had a binary outcome, and the number of patients with at least 14 disability days was 238, at least 1 ED visit was 134, or at least 1 mental health visit was 72. Thus, a 10:1 independent variable to outcome event ratio was achieved for 2 of these 3 models. Finally, somatic symptom burden was significantly associated with disability but not with the 2 measures of health care use that we modeled. However, in the health care use models, the absolute differences in mean somatic symptom burden between ED users and nonusers (19.8 vs 17.6 on the 44-point scale) and between mental health users and nonusers (20.3 vs 17.9) were small. Thus, the relationship between somatic symptom burden and health care use in this sample seemed to be clinically and statistically insignificant.

The prevalence of symptoms was high: 15 of the 22 symptoms assessed were reported at rates greater than 50%, and 14 of the symptoms were each reported as very bothersome by more than 20% of patients. The fact that fatigue, sleep concerns, memory impairment, and musculoskeletal pain were the most common symptoms may be partly due to the fact all of the patients were enrolled for pain or depression: the first 3 symptoms are core criteria in diagnosing depression, and musculoskeletal pain accounts for more than two-thirds of pain concerns in clinical and population samples. However, these symptoms have also proved to be among the most common in previous studies of symptom prevalence in patients with cancer.11,1318,54 Also, many symptoms that are neither pain concerns nor core criteria for depressive disorders were common in this sample.

In addition to symptom prevalence being high, a substantial percentage of patients noted that they were bothered a lot by their symptoms, regardless of type of symptom. In a palliative care study,16 more than half of the somatic symptoms were rated as moderate to severe, yet two-thirds of severe symptoms were not volunteered by patients but rather were identified by systematic assessment. In the present study, the proportion of symptoms rated as severe was higher for some symptoms than for others. When patients report multiple symptoms, the assessment of severity coupled with patient preferences and concerns are important considerations in making treatment decisions.

The somatic symptom burden was similar not only across various types of cancer but also across different phases of cancer. Why did patients with cancer who were disease free or simply undergoing maintenance therapy report similar levels of somatic symptoms as those with newly diagnosed cancer or recurrent or progressive cancer? One important reason is that the patients in this study already had pain, depression, or both, factors themselves associated with a high somatic symptom burden. Also, in contrast to patients with cancer undergoing active treatment, those who are disease free or doing well on maintenance therapy but who are still willing to enroll in a clinical trial may be more likely to be a selected group with long-term symptoms or problems.

The study patients experienced substantial disability, reporting almost 17 of the past 28 days (60.7%) as either bed days or days in which they had to reduce their usual activities by at least 50%. The somatic symptom burden was associated with a disability scale score and the number of self-reported disability days. Moreover, somatic symptoms had an independent effect on disability even after adjusting for depression and pain severity, sociodemographic characteristics, and medical comorbidity. Indeed, multivariable models revealed that certain factors, such as age, medical comorbidity, and adverse socioeconomic disadvantage, were not associated with disability when controlling for somatic symptom burden and depression. The strong association between the number and severity of somatic symptoms and functional impairment is well established in primary care patients and other populations with chronic medical disorders.6,34

In contrast to its association with disability, somatic symptom burden was not associated with health care use. This differs from some studies5,7,55,56 in which patients with a high somatic symptom burden use a disproportionate amount of health care services. One reason for a lack of association in the present study may be that baseline health care use was already high in this sample: 80% of patients had cancer under active treatment, either newly diagnosed or recurrent/progressive. In unselected primary care populations where many patients have low annual visit rates, the subgroup with multiple somatic symptoms may distinguish itself by higher health care use. Also, somatic symptom burden might be related to excess health care use in a different sample of patients with cancer, for example, a sample in which more patients are disease free or undergoing maintenance therapy only or in which fewer patients experience pain or depression. However, neither pain severity nor depression was associated with health care use in the multivariable models.

Two other types of research regarding somatic symptoms should be mentioned in the context of this study. The first is the extensive literature on somatization. Whereas somatization has traditionally referred to the reporting of multiple somatic symptoms that lack an adequate medical explanation and are related instead to psychological factors, recent research suggests that an interaction between medical and psychological factors (rather than an “either/or” dichotomy) contributes to the experiencing and reporting of somatic symptoms.2,57,58 Indeed, even symptoms considered to be disease specific (eg, chest pain in cardiac disease, dyspnea in pulmonary disorders, and pain in arthritis) may be accounted for as much by comorbid depression and anxiety as by the physiologic severity of the underlying medical disorder.4 Similarly, an interplay of medical and psychological factors has been found for symptoms reported by patients with other chronic medical disorders.53 Indeed, somatic, anxiety, and depressive symptoms (the “SAD” triad) have been found to have overlapping and independent effects on one another and on functional status and quality-of-life outcomes.59 Many factors can account for the somatic symptom burden in patients with cancer, including the type and severity of cancer, spread to other organs, and adverse effects of therapy. At the same time, the degree to which somatization may contribute to somatic symptom burden in some patients with cancer, and the effect of psychological factors and a patient's premorbid symptom reporting history, warrants further research beyond the few studies reported to date.2529

A second type of research relevant to this study is that on symptom clusters in patients with cancer. A symptom cluster is typically defined as 2 or more concurrent symptoms.60,61 The present study findings indicate that patients with cancer pain or depression were experiencing multiple additional symptoms, or symptom clusters. Analytic strategies, such as factor analysis and cluster analysis, have been used to define which symptoms commonly co-occur in patients with cancer.60,62 We did not apply such analytic strategies to these data for 2 reasons. First, this study sample was unique in that patients had to report pain or depression, and almost half reported both symptoms at study enrollment. Second, this study sample was otherwise heterogeneous for cancer type and phase and symptoms. Because the particular symptoms being experienced were likely to vary by cancer type or phase (eg, acute treatment effects vs late effects), it is likely that we would have found multiple different symptom clusters, each with their own set of specific symptoms.

This study has several limitations. First, the associations between somatic symptom burden and disability cannot yet be assumed to be causal owing to the cross-sectional nature of the analyses. Conceptually, however, it makes sense that at least part of the directionality is a higher somatic symptom burden producing greater disability rather than the converse (ie, disability exclusively leading to higher symptom reporting). Alternatively, an unmeasured confounder could explain some of the associations. Second, we enrolled patients with a wide range of cancer types and phases, which increases the generalizability of the findings but also decreases our ability to draw firm conclusions about any one type or phase of cancer. Further studies of somatic symptoms in larger numbers of patients with single types or phases of cancer will be useful to verify, amplify, or modify these findings. Third, all the patients in this sample had pain, depression, or both, which could have inflated somatic symptom prevalence and disability. However, previous studies11,14,15,18 in less selected cancer populations have also documented a high prevalence of somatic symptoms. Moreover, somatic symptom burden remained associated with disability in the multivariable models even after controlling for depression and pain severity. Fourth, all the measures, including disability, were self-reported. Although other studies document the functional and work consequences of cancer, these findings would be further substantiated by independent measures of disability.

This study strengthens the case for improving the recognition and treatment of somatic symptoms in patients with cancer. If only 1 or a few symptoms predominate, symptom-specific evaluation and treatments may be warranted, understanding that evidence-based treatments are better established for some symptoms (eg, pain, depression, and nausea/vomiting) than for others (eg, fatigue, dry mouth, dizziness, and cognitive concerns). If symptoms are more numerous, persistent, or less amenable to specific treatments, more general strategies should be considered as well, such as treating comorbid depression and anxiety, assessing the patient's precancer history of symptom reporting and somatization, identifying health-related anxiety and concerns, and considering nonpharmacologic interventions, such as cognitive behavior therapy, exercise, symptom self-management, and other behavioral treatments.6368 One might also need to be careful of repeated evaluations for cancer-related or occult causes of persistent symptoms, particularly in stable, disease-free patients and in patients with multiple symptoms, persistent symptoms with recent negative workups, or a history suggesting somatization or somatoform disorders preceding their cancer diagnosis. In summary, the high prevalence of these symptoms coupled with their concomitant disability and adverse effect on quality of life makes optimized management well aligned with the Institute of Medicine report on improving the cancer care of the whole patient.69

Correspondence: Kurt Kroenke, MD, Regenstrief Institute Inc, 1050 Wishard Blvd, Sixth Floor, Indianapolis, IN 46202 (kkroenke@regenstrief.org).

Accepted for Publication: March 8, 2010.

Author Contributions: Drs Kroenke and Tu and Mr Wu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Kroenke, Theobald, Tu, and Carpenter. Acquisition of data: Kroenke and Theobald. Analysis and interpretation of data: Kroenke, Zhong, Wu, Tu, and Carpenter. Drafting of the manuscript: Kroenke, Zhong, and Carpenter. Critical revision of the manuscript for important intellectual content: Kroenke, Theobald, Wu, Tu, and Carpenter. Statistical analysis: Wu and Tu. Obtained funding: Kroenke. Administrative, technical, and material support: Kroenke, Zhong, Theobald, and Carpenter. Study supervision: Theobald and Tu.

Financial Disclosure: Dr Kroenke has received research funding and honoraria as a consultant or advisory board member from Eli Lilly, Pfizer, and Forest Laboratories.

Funding/Support: This study was supported by grant R01 CA-115369 from the National Cancer Institute (Dr Kroenke).

This article was corrected online for typographical errors on October 11, 2010.

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Sha  MCCallahan  CMCounsell  SRWestmoreland  GRStump  TEKroenke  K Physical symptoms as a predictor of health care use and mortality among older adults. Am J Med 2005;118 (3) 301- 306
PubMed Link to Article
Funch  DP Predictors and consequences of symptom reporting behaviors in colorectal cancer patients. Med Care 1988;26 (10) 1000- 1008
PubMed Link to Article
Curtis  EBKrech  RWalsh  TD Common symptoms in patients with advanced cancer. J Palliat Care 1991;7 (2) 25- 29
PubMed
Grond  SZech  DDiefenbach  CBischoff  A Prevalence and pattern of symptoms in patients with cancer pain: a prospective evaluation of 1635 cancer patients referred to a pain clinic. J Pain Symptom Manage 1994;9 (6) 372- 382
PubMed Link to Article
Portenoy  RKThaler  HTKornblith  AB  et al.  Symptom prevalence, characteristics and distress in a cancer population. Qual Life Res 1994;3 (3) 183- 189
PubMed Link to Article
Donnelly  SWalsh  DRybicki  L The symptoms of advanced cancer: identification of clinical and research priorities by assessment of prevalence and severity. J Palliat Care 1995;11 (1) 27- 32
PubMed
Vainio  AAuvinen  ASymptom Prevalence Group, Prevalence of symptoms among patients with advanced cancer: an international collaborative study. J Pain Symptom Manage 1996;12 (1) 3- 10
PubMed Link to Article
Chang  VTHwang  SSFeuerman  MKasimis  BS Symptom and quality of life survey of medical oncology patients at a veterans affairs medical center: a role for symptom assessment. Cancer 2000;88 (5) 1175- 1183
PubMed Link to Article
Cleeland  CSMendoza  TRWang  XS  et al.  Assessing symptom distress in cancer patients: the M.D. Anderson Symptom Inventory. Cancer 2000;89 (7) 1634- 1646
PubMed Link to Article
Homsi  JWalsh  DRivera  N  et al.  Symptom evaluation in palliative medicine: patient report vs systematic assessment. Support Care Cancer 2006;14 (5) 444- 453
PubMed Link to Article
Teunissen  SCWesker  WKruitwagen  Cde Haes  HCVoest  EEde Graeff  A Symptom prevalence in patients with incurable cancer: a systematic review. J Pain Symptom Manage 2007;34 (1) 94- 104
PubMed Link to Article
Yamagishi  AMorita  TMiyashita  MKimura  F Symptom prevalence and longitudinal follow-up in cancer outpatients receiving chemotherapy. J Pain Symptom Manage 2009;37 (5) 823- 830
PubMed Link to Article
Dodd  MJMiaskowski  CPaul  SM Symptom clusters and their effect on the functional status of patients with cancer. Oncol Nurs Forum 2001;28 (3) 465- 470
PubMed
Fox  SWLyon  DE Symptom clusters and quality of life in survivors of lung cancer. Oncol Nurs Forum 2006;33 (5) 931- 936
PubMed Link to Article
Given  BAGiven  CWSikorskii  AHadar  N Symptom clusters and physical function for patients receiving chemotherapy. Semin Oncol Nurs 2007;23 (2) 121- 126
PubMed Link to Article
Ferreira  KAKimura  MTeixeira  MJ  et al.  Impact of cancer-related symptom synergisms on health-related quality of life and performance status. J Pain Symptom Manage 2008;35 (6) 604- 616
PubMed Link to Article
Hadi  SFan  GHird  AEKirou-Mauro  AFilipczak  LAChow  E Symptom clusters in patients with cancer with metastatic bone pain. J Palliat Med 2008;11 (4) 591- 600
PubMed Link to Article
Foley  KM The relationship of pain and symptom management to patient requests for physician-assisted suicide. J Pain Symptom Manage 1991;6 (5) 289- 297
PubMed Link to Article
Chaturvedi  SKHopwood  PMaguire  P Non-organic somatic symptoms in cancer. Eur J Cancer 1993;29A (7) 1006- 1008
PubMed Link to Article
Chaturvedi  SKMaguire  GP Persistent somatization in cancer: a controlled follow-up study. J Psychosom Res 1998;45 (3) 249- 256
PubMed Link to Article
Chaturvedi  SKPeter Maguire  GSomashekar  BS Somatization in cancer. Int Rev Psychiatry 2006;18 (1) 49- 54
PubMed Link to Article
Akechi  TNakano  TAkizuki  N  et al.  Somatic symptoms for diagnosing major depression in cancer patients. Psychosomatics 2003;44 (3) 244- 248
PubMed Link to Article
Novy  DBerry  MPPalmer  JLMensing  CWilley  JBruera  E Somatic symptoms in patients with chronic non-cancer-related and cancer-related pain. J Pain Symptom Manage 2005;29 (6) 603- 612
PubMed Link to Article
Reid  SWessely  SCrayford  THotopf  M Medically unexplained symptoms in frequent attenders of secondary health care: retrospective cohort study. BMJ 2001;322 (7289) 767
PubMed Link to Article
Kroenke  KTheobald  DNorton  K  et al.  The Indiana Cancer Pain and Depression (INCPAD) trial Design of a telecare management intervention for cancer-related symptoms and baseline characteristics of study participants. Gen Hosp Psychiatry 2009;31 (3) 240- 253
PubMed Link to Article
Kroenke  KSpitzer  RL The PHQ-9: a new depression and diagnostic severity measure. Psychiatr Ann 2002;32509- 521
Link to Article
Kroenke  KStrine  TWSpitzer  RLWilliams  JBBerry  JTMokdad  AH The PHQ-8 as a measure of current depression in the general population. J Affect Disord 2009;114 (1-3) 163- 173
PubMed Link to Article
Kroenke  KSpitzer  RLWilliams  JBW The PHQ-15: validity of a new measure for evaluating the severity of somatic symptoms. Psychosom Med 2002;64 (2) 258- 266
PubMed Link to Article
Portenoy  RKThaler  HTKornblith  AB  et al.  The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress. Eur J Cancer 1994;30A (9) 1326- 1336
PubMed Link to Article
Sheehan  DVHarnett-Sheehan  KRaj  BA The measurement of disability. Int Clin Psychopharmacol 1996;11 ((suppl 3)) 89- 95
PubMed Link to Article
Leon  ACOlfson  MPortera  LFarber  LSheehan  DV Assessing psychiatric impairment in primary care with the Sheehan Disability Scale. Int J Psychiatry Med 1997;27 (2) 93- 105
PubMed Link to Article
Arbuckle  RFrye  MABrecher  M  et al.  The psychometric validation of the Sheehan Disability Scale (SDS) in patients with bipolar disorder. Psychiatry Res 2009;165 (1-2) 163- 174
PubMed Link to Article
Sheehan  KHSheehan  DV Assessing treatment effects in clinical trials with the discan metric of the Sheehan Disability Scale. Int Clin Psychopharmacol 2008;23 (2) 70- 83
PubMed Link to Article
Rost  KNutting  PSmith  JWerner  JDuan  N Improving depression outcomes in community primary care practice: a randomized trial of the quEST intervention. J Gen Intern Med 2001;16 (3) 143- 149
PubMed Link to Article
Cleeland  CSGonin  RHatfield  AK  et al.  Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 1994;330 (9) 592- 596
PubMed Link to Article
Kroenke  KBair  MJDamush  TM  et al.  Optimized antidepressant therapy and pain self-management in primary care patients with depression and musculoskeletal pain: a randomized controlled trial. JAMA 2009;301 (20) 2099- 2110
PubMed Link to Article
Unützer  JKaton  WCallahan  CM  et al. IMPACT Investigators, Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial. JAMA 2002;288 (22) 2836- 2845
PubMed Link to Article
Kroenke  KSpitzer  RLWilliams  JBWMonahan  POLöwe  B Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med 2007;146 (5) 317- 325
PubMed Link to Article
Perkins  AJKroenke  KUnützer  J  et al.  Common comorbidity scales were similar in their ability to predict health care costs and mortality. J Clin Epidemiol 2004;57 (10) 1040- 1048
PubMed Link to Article
Brown  LFKroenke  KTheobald  DEWu  JTu  W The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology 2010;19 (7) 734- 741
PubMed Link to Article
Löwe  BUnützer  JCallahan  CMPerkins  AJKroenke  K Monitoring depression treatment outcomes with the patient health questionnaire-9. Med Care 2004;42 (12) 1194- 1201
PubMed Link to Article
Kazis  LEAnderson  JJMeenan  RF Effect sizes for interpreting changes in health status. Med Care 1989;27 (3) ((suppl)) S178- S189
PubMed Link to Article
Carr  DGoudas  LLawrence  D  et al.  Management of Cancer Symptoms: Pain, Depression, and Fatigue.  Rockville, MD Agency for Healthcare Research and Quality2002; Evidence Report/Technology Assessment No. 61; AHRQ publication 02-E032
Bottomley  A Depression in cancer patients: a literature review. Eur J Cancer Care (Engl) 1998;7 (3) 181- 191
PubMed Link to Article
Caraceni  APortenoy  RKInternational Association for the Study of Pain, An international survey of cancer pain characteristics and syndromes: IASP Task Force on Cancer Pain. Pain 1999;82 (3) 263- 274
PubMed Link to Article
Portenoy  RKLesage  P Management of cancer pain. Lancet 1999;353 (9165) 1695- 1700
PubMed Link to Article
Kroenke  K The interface between physical and psychological symptoms. J Clin Psychiatry Primary Care Companion J Clin Psychiatry 2003;5 ((suppl 7)) 11- 18
Patrick  DLFerketich  SLFrame  PS  et al. National Institutes of Health State-of-the-Science Panel, National Institutes of Health State-of-the-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 15-17, 2002. J Natl Cancer Inst 2003;95 (15) 1110- 1117
PubMed Link to Article
Kroenke  KSpitzer  RLdeGruy  FV  IIISwindle  R A symptom checklist to screen for somatoform disorders in primary care. Psychosomatics 1998;39 (3) 263- 272
PubMed Link to Article
Rief  WMartin  AKlaiberg  ABrähler  E Specific effects of depression, panic, and somatic symptoms on illness behavior. Psychosom Med 2005;67 (4) 596- 601
PubMed Link to Article
Kroenke  KSharpe  MSykes  R Revising the classification of somatoform disorders: key questions and preliminary recommendations. Psychosomatics 2007;48 (4) 277- 285
PubMed Link to Article
Kroenke  K Somatoform disorders and recent diagnostic controversies. Psychiatr Clin North Am 2007;30 (4) 593- 619
PubMed Link to Article
Löwe  BSpitzer  RLWilliams  JBMussell  MSchellberg  DKroenke  K Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment. Gen Hosp Psychiatry 2008;30 (3) 191- 199
PubMed Link to Article
Barsevick  AM The elusive concept of the symptom cluster. Oncol Nurs Forum 2007;34 (5) 971- 980
PubMed Link to Article
Barsevick  AMWhitmer  KNail  LMBeck  SLDudley  WN Symptom cluster research: conceptual, design, measurement, and analysis issues. J Pain Symptom Manage 2006;31 (1) 85- 95
PubMed Link to Article
Barsevick  AM The concept of symptom cluster. Semin Oncol Nurs 2007;23 (2) 89- 98
PubMed Link to Article
Raine  RHaines  ASensky  THutchings  ALarkin  KBlack  N Systematic review of mental health interventions for patients with common somatic symptoms: can research evidence from secondary care be extrapolated to primary care? BMJ 2002;325 (7372) 1082- 1085
PubMed Link to Article
Smith  RCLein  CCollins  C  et al.  Treating patients with medically unexplained symptoms in primary care. J Gen Intern Med 2003;18 (6) 478- 489
PubMed Link to Article
Jackson  JLO’Malley  PGKroenke  K Antidepressants and cognitive-behavioral therapy for symptom syndromes. CNS Spectr 2006;11 (3) 212- 222
PubMed
Henningsen  PZipfel  SHerzog  W Management of functional somatic syndromes. Lancet 2007;369 (9565) 946- 955
PubMed Link to Article
Kroenke  K Efficacy of treatment for somatoform disorders: a review of randomized controlled trials. Psychosom Med 2007;69 (9) 881- 888
PubMed Link to Article
Jacobsen  PBJim  HS Psychosocial interventions for anxiety and depression in adult cancer patients: achievements and challenges. CA Cancer J Clin 2008;58 (4) 214- 230
PubMed Link to Article
 Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs. CommitteeonPsychosocialServicestoCancerPatients/FamiliesinaCommunitySetting. Washington, DC National Academies Press2008;

Figures

Tables

Table Graphic Jump LocationTable 1. Somatic Symptom Prevalence and Severity in 405 Patients With Cancer and Comorbid Pain, Depression, or Both
Table Graphic Jump LocationTable 2. Bivariate Associations of Somatic Symptom Burden Score With Sociodemographic Characteristics and Health Care Use
Table Graphic Jump LocationTable 3. Mean (SD) Somatic Symptom Burden Scores by Type and Phase of Cancer
Table Graphic Jump LocationTable 4. Multivariable Correlates of Disability in Patients With Cancer and Comorbid Pain, Depression, or Botha

References

Kroenke  KLaine  C Investigating symptoms: frontiers in primary care research. Ann Intern Med 2001;134 (9, pt 2) 800- 930
Kroenke  KRosmalen  JG Symptoms, syndromes, and the value of psychiatric diagnostics in patients who have functional somatic disorders. Med Clin North Am 2006;90 (4) 603- 626
PubMed Link to Article
Kroenke  K Patients presenting with somatic complaints: epidemiology, psychiatric comorbidity and management. Int J Methods Psychiatr Res 2003;12 (1) 34- 43
PubMed Link to Article
Katon  WLin  EHKroenke  K The association of depression and anxiety with medical symptom burden in patients with chronic medical illness. Gen Hosp Psychiatry 2007;29 (2) 147- 155
PubMed Link to Article
Barsky  AJOrav  EJBates  DW Somatization increases medical utilization and costs independent of psychiatric and medical comorbidity. Arch Gen Psychiatry 2005;62 (8) 903- 910
PubMed Link to Article
Harris  AMOrav  EJBates  DWBarsky  AJ Somatization increases disability independent of comorbidity. J Gen Intern Med 2009;24 (2) 155- 161
PubMed Link to Article
Sha  MCCallahan  CMCounsell  SRWestmoreland  GRStump  TEKroenke  K Physical symptoms as a predictor of health care use and mortality among older adults. Am J Med 2005;118 (3) 301- 306
PubMed Link to Article
Funch  DP Predictors and consequences of symptom reporting behaviors in colorectal cancer patients. Med Care 1988;26 (10) 1000- 1008
PubMed Link to Article
Curtis  EBKrech  RWalsh  TD Common symptoms in patients with advanced cancer. J Palliat Care 1991;7 (2) 25- 29
PubMed
Grond  SZech  DDiefenbach  CBischoff  A Prevalence and pattern of symptoms in patients with cancer pain: a prospective evaluation of 1635 cancer patients referred to a pain clinic. J Pain Symptom Manage 1994;9 (6) 372- 382
PubMed Link to Article
Portenoy  RKThaler  HTKornblith  AB  et al.  Symptom prevalence, characteristics and distress in a cancer population. Qual Life Res 1994;3 (3) 183- 189
PubMed Link to Article
Donnelly  SWalsh  DRybicki  L The symptoms of advanced cancer: identification of clinical and research priorities by assessment of prevalence and severity. J Palliat Care 1995;11 (1) 27- 32
PubMed
Vainio  AAuvinen  ASymptom Prevalence Group, Prevalence of symptoms among patients with advanced cancer: an international collaborative study. J Pain Symptom Manage 1996;12 (1) 3- 10
PubMed Link to Article
Chang  VTHwang  SSFeuerman  MKasimis  BS Symptom and quality of life survey of medical oncology patients at a veterans affairs medical center: a role for symptom assessment. Cancer 2000;88 (5) 1175- 1183
PubMed Link to Article
Cleeland  CSMendoza  TRWang  XS  et al.  Assessing symptom distress in cancer patients: the M.D. Anderson Symptom Inventory. Cancer 2000;89 (7) 1634- 1646
PubMed Link to Article
Homsi  JWalsh  DRivera  N  et al.  Symptom evaluation in palliative medicine: patient report vs systematic assessment. Support Care Cancer 2006;14 (5) 444- 453
PubMed Link to Article
Teunissen  SCWesker  WKruitwagen  Cde Haes  HCVoest  EEde Graeff  A Symptom prevalence in patients with incurable cancer: a systematic review. J Pain Symptom Manage 2007;34 (1) 94- 104
PubMed Link to Article
Yamagishi  AMorita  TMiyashita  MKimura  F Symptom prevalence and longitudinal follow-up in cancer outpatients receiving chemotherapy. J Pain Symptom Manage 2009;37 (5) 823- 830
PubMed Link to Article
Dodd  MJMiaskowski  CPaul  SM Symptom clusters and their effect on the functional status of patients with cancer. Oncol Nurs Forum 2001;28 (3) 465- 470
PubMed
Fox  SWLyon  DE Symptom clusters and quality of life in survivors of lung cancer. Oncol Nurs Forum 2006;33 (5) 931- 936
PubMed Link to Article
Given  BAGiven  CWSikorskii  AHadar  N Symptom clusters and physical function for patients receiving chemotherapy. Semin Oncol Nurs 2007;23 (2) 121- 126
PubMed Link to Article
Ferreira  KAKimura  MTeixeira  MJ  et al.  Impact of cancer-related symptom synergisms on health-related quality of life and performance status. J Pain Symptom Manage 2008;35 (6) 604- 616
PubMed Link to Article
Hadi  SFan  GHird  AEKirou-Mauro  AFilipczak  LAChow  E Symptom clusters in patients with cancer with metastatic bone pain. J Palliat Med 2008;11 (4) 591- 600
PubMed Link to Article
Foley  KM The relationship of pain and symptom management to patient requests for physician-assisted suicide. J Pain Symptom Manage 1991;6 (5) 289- 297
PubMed Link to Article
Chaturvedi  SKHopwood  PMaguire  P Non-organic somatic symptoms in cancer. Eur J Cancer 1993;29A (7) 1006- 1008
PubMed Link to Article
Chaturvedi  SKMaguire  GP Persistent somatization in cancer: a controlled follow-up study. J Psychosom Res 1998;45 (3) 249- 256
PubMed Link to Article
Chaturvedi  SKPeter Maguire  GSomashekar  BS Somatization in cancer. Int Rev Psychiatry 2006;18 (1) 49- 54
PubMed Link to Article
Akechi  TNakano  TAkizuki  N  et al.  Somatic symptoms for diagnosing major depression in cancer patients. Psychosomatics 2003;44 (3) 244- 248
PubMed Link to Article
Novy  DBerry  MPPalmer  JLMensing  CWilley  JBruera  E Somatic symptoms in patients with chronic non-cancer-related and cancer-related pain. J Pain Symptom Manage 2005;29 (6) 603- 612
PubMed Link to Article
Reid  SWessely  SCrayford  THotopf  M Medically unexplained symptoms in frequent attenders of secondary health care: retrospective cohort study. BMJ 2001;322 (7289) 767
PubMed Link to Article
Kroenke  KTheobald  DNorton  K  et al.  The Indiana Cancer Pain and Depression (INCPAD) trial Design of a telecare management intervention for cancer-related symptoms and baseline characteristics of study participants. Gen Hosp Psychiatry 2009;31 (3) 240- 253
PubMed Link to Article
Kroenke  KSpitzer  RL The PHQ-9: a new depression and diagnostic severity measure. Psychiatr Ann 2002;32509- 521
Link to Article
Kroenke  KStrine  TWSpitzer  RLWilliams  JBBerry  JTMokdad  AH The PHQ-8 as a measure of current depression in the general population. J Affect Disord 2009;114 (1-3) 163- 173
PubMed Link to Article
Kroenke  KSpitzer  RLWilliams  JBW The PHQ-15: validity of a new measure for evaluating the severity of somatic symptoms. Psychosom Med 2002;64 (2) 258- 266
PubMed Link to Article
Portenoy  RKThaler  HTKornblith  AB  et al.  The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress. Eur J Cancer 1994;30A (9) 1326- 1336
PubMed Link to Article
Sheehan  DVHarnett-Sheehan  KRaj  BA The measurement of disability. Int Clin Psychopharmacol 1996;11 ((suppl 3)) 89- 95
PubMed Link to Article
Leon  ACOlfson  MPortera  LFarber  LSheehan  DV Assessing psychiatric impairment in primary care with the Sheehan Disability Scale. Int J Psychiatry Med 1997;27 (2) 93- 105
PubMed Link to Article
Arbuckle  RFrye  MABrecher  M  et al.  The psychometric validation of the Sheehan Disability Scale (SDS) in patients with bipolar disorder. Psychiatry Res 2009;165 (1-2) 163- 174
PubMed Link to Article
Sheehan  KHSheehan  DV Assessing treatment effects in clinical trials with the discan metric of the Sheehan Disability Scale. Int Clin Psychopharmacol 2008;23 (2) 70- 83
PubMed Link to Article
Rost  KNutting  PSmith  JWerner  JDuan  N Improving depression outcomes in community primary care practice: a randomized trial of the quEST intervention. J Gen Intern Med 2001;16 (3) 143- 149
PubMed Link to Article
Cleeland  CSGonin  RHatfield  AK  et al.  Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 1994;330 (9) 592- 596
PubMed Link to Article
Kroenke  KBair  MJDamush  TM  et al.  Optimized antidepressant therapy and pain self-management in primary care patients with depression and musculoskeletal pain: a randomized controlled trial. JAMA 2009;301 (20) 2099- 2110
PubMed Link to Article
Unützer  JKaton  WCallahan  CM  et al. IMPACT Investigators, Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial. JAMA 2002;288 (22) 2836- 2845
PubMed Link to Article
Kroenke  KSpitzer  RLWilliams  JBWMonahan  POLöwe  B Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med 2007;146 (5) 317- 325
PubMed Link to Article
Perkins  AJKroenke  KUnützer  J  et al.  Common comorbidity scales were similar in their ability to predict health care costs and mortality. J Clin Epidemiol 2004;57 (10) 1040- 1048
PubMed Link to Article
Brown  LFKroenke  KTheobald  DEWu  JTu  W The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology 2010;19 (7) 734- 741
PubMed Link to Article
Löwe  BUnützer  JCallahan  CMPerkins  AJKroenke  K Monitoring depression treatment outcomes with the patient health questionnaire-9. Med Care 2004;42 (12) 1194- 1201
PubMed Link to Article
Kazis  LEAnderson  JJMeenan  RF Effect sizes for interpreting changes in health status. Med Care 1989;27 (3) ((suppl)) S178- S189
PubMed Link to Article
Carr  DGoudas  LLawrence  D  et al.  Management of Cancer Symptoms: Pain, Depression, and Fatigue.  Rockville, MD Agency for Healthcare Research and Quality2002; Evidence Report/Technology Assessment No. 61; AHRQ publication 02-E032
Bottomley  A Depression in cancer patients: a literature review. Eur J Cancer Care (Engl) 1998;7 (3) 181- 191
PubMed Link to Article
Caraceni  APortenoy  RKInternational Association for the Study of Pain, An international survey of cancer pain characteristics and syndromes: IASP Task Force on Cancer Pain. Pain 1999;82 (3) 263- 274
PubMed Link to Article
Portenoy  RKLesage  P Management of cancer pain. Lancet 1999;353 (9165) 1695- 1700
PubMed Link to Article
Kroenke  K The interface between physical and psychological symptoms. J Clin Psychiatry Primary Care Companion J Clin Psychiatry 2003;5 ((suppl 7)) 11- 18
Patrick  DLFerketich  SLFrame  PS  et al. National Institutes of Health State-of-the-Science Panel, National Institutes of Health State-of-the-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 15-17, 2002. J Natl Cancer Inst 2003;95 (15) 1110- 1117
PubMed Link to Article
Kroenke  KSpitzer  RLdeGruy  FV  IIISwindle  R A symptom checklist to screen for somatoform disorders in primary care. Psychosomatics 1998;39 (3) 263- 272
PubMed Link to Article
Rief  WMartin  AKlaiberg  ABrähler  E Specific effects of depression, panic, and somatic symptoms on illness behavior. Psychosom Med 2005;67 (4) 596- 601
PubMed Link to Article
Kroenke  KSharpe  MSykes  R Revising the classification of somatoform disorders: key questions and preliminary recommendations. Psychosomatics 2007;48 (4) 277- 285
PubMed Link to Article
Kroenke  K Somatoform disorders and recent diagnostic controversies. Psychiatr Clin North Am 2007;30 (4) 593- 619
PubMed Link to Article
Löwe  BSpitzer  RLWilliams  JBMussell  MSchellberg  DKroenke  K Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment. Gen Hosp Psychiatry 2008;30 (3) 191- 199
PubMed Link to Article
Barsevick  AM The elusive concept of the symptom cluster. Oncol Nurs Forum 2007;34 (5) 971- 980
PubMed Link to Article
Barsevick  AMWhitmer  KNail  LMBeck  SLDudley  WN Symptom cluster research: conceptual, design, measurement, and analysis issues. J Pain Symptom Manage 2006;31 (1) 85- 95
PubMed Link to Article
Barsevick  AM The concept of symptom cluster. Semin Oncol Nurs 2007;23 (2) 89- 98
PubMed Link to Article
Raine  RHaines  ASensky  THutchings  ALarkin  KBlack  N Systematic review of mental health interventions for patients with common somatic symptoms: can research evidence from secondary care be extrapolated to primary care? BMJ 2002;325 (7372) 1082- 1085
PubMed Link to Article
Smith  RCLein  CCollins  C  et al.  Treating patients with medically unexplained symptoms in primary care. J Gen Intern Med 2003;18 (6) 478- 489
PubMed Link to Article
Jackson  JLO’Malley  PGKroenke  K Antidepressants and cognitive-behavioral therapy for symptom syndromes. CNS Spectr 2006;11 (3) 212- 222
PubMed
Henningsen  PZipfel  SHerzog  W Management of functional somatic syndromes. Lancet 2007;369 (9565) 946- 955
PubMed Link to Article
Kroenke  K Efficacy of treatment for somatoform disorders: a review of randomized controlled trials. Psychosom Med 2007;69 (9) 881- 888
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