Major Depression, Generalized Anxiety Disorder, and Panic Disorder in Patients Scheduled for Knee Arthroplasty

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1 The Journal of Arthroplasty Vol. 25 No Major Depression, Generalized Anxiety Disorder, and Panic Disorder in Patients Scheduled for Knee Arthroplasty Daniel L. Riddle, PT, PhD, FAPTA,*y James B. Wade, PhD,z and William A. Jiranek, MDy Abstract: The aim of this study is to determine the prevalence and correlates of major depression, generalized anxiety disorder, and panic disorder in patients scheduled for knee arthroplasty. Three hundred nine patients completed questionnaires and validated self-report measures of major depression, generalized anxiety, and panic disorder. Stepwise multivariable logistic regression identified preoperative predictors of major depression and generalized anxiety disorder. The prevalence of major depression was 22.5% (95% confidence interval [CI], 18%-28%). For generalized anxiety disorder, prevalence was 20.2% (95% CI, 16%-25%), and for panic disorder, prevalence was 4.6% (95% CI, 2.8%-7.6%). Multiple predictors for major depression and generalized anxiety disorder were found. Major depression and generalized anxiety are relatively common among patients scheduled for knee arthroplasty. Several simply assessed variables can be used to identify patients who are likely to have major depression or generalized anxiety. Keywords: major depression, generalized anxiety disorder, panic disorder Elsevier Inc. All rights reserved. Knee arthroplasty is generally a safe and cost-effective procedure for reducing pain and increasing physical function in patients with advanced knee osteoarthritis or rheumatoid arthritis [1]. Multiple large sample cohort studies have demonstrated large therapeutic effects on pain and physical function 6 months to 7 years after the procedure [2-4]. The number of patients undergoing knee arthroplasty has grown dramatically. For example, trend data reported by Kurtz et al [5] suggest that by 2010, approximately knee arthroplasty surgeries will be conducted annually. Although cohort studies indicate knee arthroplasty is generally effective, some patients respond poorly to surgery. For example, Escobar et al [6] found that 33% From the *Department of Physical Therapy, Virginia Commonwealth University, Richmond, Virginia; ydepartment of Orthopaedic Surgery, Virginia Commonwealth University, Richmond, Virginia; zdepartment of Psychiatry, Virginia Commonwealth University, Richmond, Virginia; Department of Neurology, Virginia Commonwealth University, Richmond, Virginia; and Department of Anaesthesiology, Virginia Commonwealth University, Richmond, Virginia. Submitted December 30, 2008; accepted April 4, Benefits or funds were received in partial or total support of AD Williams Research Grant Fund from Virginia Commonwealth University. Reprint requests: Daniel L. Riddle, PT, PhD, FAPTA, Department of Physical Therapy, Virginia Commonwealth University, PO Box , Richmond, VA Elsevier Inc. All rights reserved / $36.00/0 doi: /j.arth of patients (n = 423) did not have measurable improvements in pain 6 months after surgery. Brander et al [7] reported that 19% of patients in their cohort of 116 patients reported moderate to severe pain 6 months after surgery. Murray and Frost [8] found that 30% of their large cohort of 1429 patients had moderate or severe pain 1 year after knee arthroplasty. With regard to physical function, only a third of patients report no functional problems with the surgical knee [9], and approximately 20% report dissatisfaction with their functional ability a year or more after surgery [10]. Chronic pain, a common finding in patients scheduled for knee arthroplasty [2], is often associated with psychiatric disorders. Clarifying the relationship between pain and emotional suffering is important because several studies have suggested that patients experiencing chronic pain with comorbid psychiatric disorders have poorer outcome and increased disability [11-13]. Most of the studies examining the association between psychiatric disorders and pain have focused on depression [14-16]. In comparison with nondepressed patients with pain, depressed chronic pain sufferers, irrespective of pain etiology, experience greater pain sensation intensity, more pain-related disability, and poorer treatment response [17,18]. Furthermore, the influence of depression on functional status has been shown to be independent of pain severity [19,20]. 581

2 582 The Journal of Arthroplasty Vol. 25 No. 4 June 2010 Although anxiety disorders have been associated with many nonmusculoskeletal diseases, only a few studies have examined the relationship of musculoskeletal pain with anxiety disorders [21-23]. McWilliams et al [22] studied a nationally representative sample of adults from the United States and found the association between chronic arthritis related pain and anxiety disorders or panic disorder to be stronger than for depression. In a second nationally representative study, McWilliams et al [23] found a higher prevalence of depression, panic disorder, and generalized anxiety disorder in patients with arthritis-related chronic pain compared with a representative sample of persons with pain but no arthritis. Using a large epidemiologic sample, Sareen et al [24] found anxiety disorders including panic disorder to be uniquely associated with a variety of medical conditions, and presence of a comorbid anxiety or panic disorder predicted worse SF-36 Physical Component and Mental Component scores. Despite the influence of depression and anxiety disorders on outcome or disease state, we found no study of patients with knee arthroplasty that estimated prevalence or identified demographic and disease-related correlates of generalized anxiety disorder, panic disorder, and major depression. Given that these psychiatric disorders may negatively impact on medical, social, and functional outcome, it is critical to identify the presence of these disorders before surgery. The method used by the clinician to identify patients at risk for psychiatric illness should be quick and easy to administer. Ideally, the tools could be administered by office support staff. Early identification of patients at risk for psychopathy would allow additional psychiatric resources to be directed to these individuals before surgery. The goal of this study was 2-fold: (1) to describe the prevalence of 3 of the more common mental health disorders (ie, major depression, generalized anxiety disorder, and panic disorder) that negatively impact pain and physical function and (2) to identify correlates of these 3 disorders in patients before knee arthroplasty. Materials and Methods Patient Sample Consecutive patients were recruited from the preoperative educational classes of 2 hospitals in Richmond, Va, between December 1, 2005, and April 1, One is a university hospital and tertiary care center affiliated with Virginia Commonwealth University, and the other is a suburban hospital. All patients were being treated by orthopedic surgeons affiliated with Virginia Commonwealth University. To be eligible, patients had to (a) be able to speak and understand English, (b) be scheduled for unilateral knee arthroplasty, and (c) provide informed consent by signing a form approved by the institutional review boards of Virginia Commonwealth University and St. Mary's Hospital in Richmond, Va. Measures A large number of measures were collected and were categorized as demographic, mental health, arthritis, and general health or patient self-reported pain and disability measures. Several recent systematic reviews of depression and anxiety indicate that a variety of risk factors are associated with these disorders in patients with chronic musculoskeletal conditions [25-27], and we selected our measures with this evidence in mind. Demographic Measures The patient's age, sex, height, weight, body mass index (BMI), race/ethnicity, marital status, and amount of education were collected via self-report. Self-reported height and weight have been shown to be reasonably accurate indicators of actual measures of BMI (Pearson correlation coefficient [r] = 0.89 to 0.97, depending on age) [28]. Mental Health Measures We used the Patient Health Questionnaire 8 (PHQ-8), a validated self-report measure of major depression [29]. The PHQ-8 has been shown to have a sensitivity and specificity of 88% when compared to diagnostic interviews conducted by mental health professionals [29]. Patients also completed the generalized anxiety and panic disorder modules from the Primary Care Evaluation of Mental Disorders (PRIME-MD), a validated battery of mental health tests designed for outpatients [30]. These measures have good diagnostic validity as compared to diagnoses made by mental health professionals with sensitivities and specificities ranging from 63% to 99% [30]. Criterion scores were validated for the PHQ-8 (score 10) [29] and the generalized anxiety and panic disorder measures (scored according to algorithms) [30], and we used these criterion scores to dichotomize patients in our study into those with and those without each of the 3 mental health disorders. Arthritis and General Health Patients reported how long they had knee pain and whether they had been diagnosed with rheumatoid arthritis. Patients were also asked what other areas of their body were painful, and the options were low back, neck, arm, or the nonsurgical lower extremity. The Self- Administered Comorbidity Questionnaire, a validated comorbidity questionnaire was used to quantify the extent and severity of comorbidities [31]. Pain and Disability Patients completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Function questionnaires. The WOMAC has been studied extensively and has been shown to be reliable and valid for quantifying the extent of pain and disability in patients undergoing knee arthroplasty [32,33]. We conducted separate analyses using WOMAC Pain as a predictor variable and WOMAC

3 Depression, General Anxiety Disorder, and Panic Disorder Riddle et al 583 Function as a predictor variable. WOMAC Pain and Function scores have been consistently shown to be highly correlated with Pearson r values of approximately 0.8 [34,35]. Given this high correlation, we could not place both predictor variables in 1 model because of multicollinearity. However, for patients with mental health disorders, these disorders may preferentially impact pain or function in different ways, and we wanted to be able to describe this differential effect if it exists. In addition, pain and function are highly important to patients and are 2 key variables surgeons consider when making surgical treatment decisions [1]. We therefore believed that it was important to report separate models using WOMAC Pain and Function scores as predictor variables. Data Analysis To describe the prevalence of major depression, generalized anxiety disorder, and panic disorder, we report the proportion of patients with each disorder along with 95% confidence estimates for each proportion. Data for all variables obtained on patients with and patients without either major depression or generalized anxiety were compared using χ 2 tests for categorical measures and independent sample t tests for continuous measures. To describe the correlates for each mental health disorder, we used stepwise multivariable logistic regression with backward elimination. Only variables that were significant (P b.05) in the univariate analyses were considered for main effects in the multivariable analyses. In addition, we tested for all 2-way interactions among the significant variables in the models as well as all nonsignificant variables to assure that any important relationships among variables in the study were not missed. The probability for entry into the model was set at P b.05, and the probability for removal was set at P b.10. The Hosmer-Lemeshow test was used to judge the goodness of fit for each model. The Nagelkerke R 2, a statistic that is similar to the coefficient of determination (R) for general linear regression, was used to describe the variance in the dependent variable that is explained by each model. The comorbidity variable demonstrated positive skewness and was square root transformed to create a normal distribution. All other quantitative measures were normally distributed. All analyses were conducted using SPSS, version 16 (SPSS, Chicago, Ill). Results Description of the Sample A total of 309 consecutive patients participated in the study, of which 7 did not complete the major depression measure, 12 did not complete the generalized anxiety disorder instrument, and 7 did not complete the panic disorder measure. Approximately 68% of the patients were female, and 22% were African American. The median age of the sample was 64 years. Prevalence of Mental Health Disorders A total of 68 of 302 patients met the criterion for major depression for a prevalence of 22.5% (95% confidence interval [CI] = 18%, 28%). A total of 60 of 297 patients had generalized anxiety disorder for a prevalence of 20.2% (95% CI = 16%, 25%). For panic disorder, 14 of 302 patients met the criterion for a prevalence of 4.6% (95% CI = 2.8%, 7.6%). Correlates of Mental Health Disorders Because the prevalence of panic disorder was only 4.6%, univariate comparisons and multivariable regression models of correlates of panic disorder could not be generated. Several variables were found in our univariate analysis to be associated with major depression (see Table 1). Patients who were depressed were more likely to have worse overall health, to be younger, to be African American, to be divorced or separated, to be obese, and to report being treated for depression, anxiety or stress. Table 1. Description of the Sample Divided by Depression Status Variables With Symptoms of Major Depression (n = 68) Without Major Depressive Symptoms (N = 234) P Demographic Age in years, 59.8 (9.7) 64.5 (9.6).001 mean (SD) Female 53 (77.9) 154 (66.4).07 African American 23 (33.8) 40 (17.1).003 High school 30 (45.5) 79 (34.5).10 graduate or less Divorced or 16 (23.5) 14 (6.0) b.001 separated General health Comorbidity index 9.6 (4.8) 6.0 (3.3) b.001 BMI N30 49 (73.1) 94 (41.0) b.001 Cigarette smoker 10 (14.9) 13 (5.7).01 Self report treatment 32 (48.5) 26 (11.2) b.001 for depression, anxiety, or stress Arthritis-related health Time since onset 87.1 (87.7) (102.8).25 of knee pain Rheumatoid arthritis 23 (34.3) 49 (21.3).03 Low back pain 41 (61.2) 104 (45.2).02 Lower extremity pain 41 (61.2) 83 (36.1) b.001 Neck pain 17 (25.4) 38 (16.5).10 Upper extremity pain 24 (35.8) 72 (31.3).49 Revision 6 (8.8) 20 (8.5).94 WOMAC Pain score 13.1 (3.5) 9.6 (3.7) b.001 WOMAC Function 42.3 (11.4) 29.3 (13.0) b.001 score 15 cm visual analog 10.6 (3.6) 8.7 (4.2).001 scale, pain intensity 15 cm visual analog scale, pain unpleasantness 10.7 (3.3) 8.8 (3.8) b.001

4 584 The Journal of Arthroplasty Vol. 25 No. 4 June 2010 Table 2. Multivariable Logistic Regression Model (n = 287) for Prediction of Depression Using WOMAC Pain as an Independent Variable * 95% CI for OR B SE Wald df Significance OR Lower Upper BMI Divorced or separated Self-report of psychiatric treatment b Comorbidity score WOMAC Pain Constant b OR indicates odds ratio. * Model parameters shown are raw regression coefficients (B) and standard errors, the Wald statistic with the associated degrees of freedom and significance, and the odds ratio for each variable along with 95% confidence intervals. Results from the multivariable logistic regression models for correlates of major depression are presented in Tables 2 and 3. No interactions were included in the models because there were no situations in which the explained variance improved by more than 2 percentage points beyond that explained by the main effects. In addition, because we had a relatively small number of patients with major depression or anxiety, more parsimonious models are preferred [36]. Independent correlates of major depression were obesity, being divorced or separated, having higher comorbidity scores, and a self-report of treatment for depression, anxiety, or stress. WOMAC Pain scores also predicted major depression status (see Table 2). Odds of major depression increased, on average, 17% for each point increase in WOMAC Pain. In a separate model, WOMAC Function scores also predicted major depression status with a 6% increase in odds of major depression for every point increase in the WOMAC Function score (see Table 3). Generalized anxiety disorder was also found in univariate analyses to be associated with several variables (see Table 4). Patients with generalized anxiety disorder were more likely to be female; to be obese; to have a high school degree or less; to be treated for depression, anxiety, or stress; and to have worse overall health than patients who did not have generalized anxiety disorder. When the WOMAC Pain score was considered as a predictor variable in a multivariable model for generalized anxiety disorder, it was found to be significant after adjustment for other variables (see Table 5). The other predictors were self-report of treatment for depression, anxiety, or stress and higher comorbidity scores. When WOMAC Function was tested as an independent predictor, it did not enter the model. The Hosmer-Lemeshow Goodness of Fit statistics ranged from P =.18 to P =.89, indicating that all models fit the data. The Negelkerke R 2 values were 0.42 and 0.43 for the major depression models using WOMAC Function or WOMAC Pain, respectively, and 0.29 for the generalized anxiety disorder model when including WOMAC Pain. Discussion An untreated mood or anxiety disorder in a patient with chronic pain increases suffering, may negatively impact outcome, and increases risk of suicidal behavior [37]. Given the risks associated with comorbid mental health disorders, identifying patients with these conditions early during care would appear to be optimal. The 22.5% prevalence rate for major depression and 4% prevalence rate for panic disorder are much higher than that seen in community dwelling adults [38] but are consistent with rates described in urban general medical practice settings [39] and patients with arthritis [23]. A Table 3. Multivariable Logistic Regression Model (n = 289) for Prediction of Depression Using WOMAC Function as an Independent Variable * 95% CI for OR B SE Wald df Significance OR Lower Upper BMI Divorced or separated Self-report of psychiatric treatment b Comorbidity score WOMAC Function score b Constant b OR indicates odds ratio. * Model parameters shown are raw regression coefficients (B) and standard errors, the Wald statistic with the associated degrees of freedom and significance, and the odds ratio for each variable along with 95% confidence intervals.

5 Depression, General Anxiety Disorder, and Panic Disorder Riddle et al 585 Table 4. Description of the Sample Divided by Generalized Anxiety Status Without Variables With Symptoms of Generalized Anxiety Disorder (n = 60) Generalized Anxiety Symptoms (n = 237) P Demographic Age in years, 61.6 (8.0) 64.0 (10.2).10 mean (SD) Female 49 (83.1) 153 (64.8).007 African 18 (30) 46 (19.4).07 American High school 31 (53.4) 79 (34.1).006 graduate or less Divorced 10 (16.7) 19 (8.0).04 or separated General health Comorbidity 9.1 (4.7) 6.2 (3.5) b.001 index BMI N30 37 (64.9) 105 (44.9).007 Cigarette 9 (15.5) 15 (6.4).02 smoker Self-report Tx 25 (42.4) 29 (12.2) b.001 for depression, anxiety, or stress Arthritis-related health Time since onset (111.5) 96.8 (97.1).33 of knee pain Rheumatoid 20 (34.5) 49 (20.9).03 arthritis Low back pain 33 (56.9) 109 (46.6).16 Lower extremity 35 (60.3) 85 (36.3).001 pain Neck pain 18 (31) 36 (15.4).006 Upper extremity 26 (44.8) 66 (28.2).01 pain Revision 4 (6.7) 22 (9.3).52 WOMAC Pain 12.9 (3.6) 9.7 (3.8) b.001 score WOMAC 39.0 (14.4) 30.6 (13.1) b.001 Function score 15 cm visual 10.8 (3.2) 8.7 (4.2) b.001 analog scale, pain intensity 15 cm visual analog scale, pain unpleasantness 11.3 (2.7) 8.8 (3.9) b.001 more recently published study of a nationally representative sample of patients with arthritis found an incidence of major depression of 9.8% [40]. The 20.5% prevalence rate for generalized anxiety disorder was much higher than the 5.6% rate reported by McWilliams et al [23] and the 5.9% reported by He et al [41] for patients with arthritis and the 7.5% prevalence for 965 primary care patients assessed by Kroenke et al [42]. We suspect that a potential explanation for the higher prevalence of generalized anxiety and major depression relative to other estimates reported in the literature is that our patients likely had much higher levels of pain and functional loss than patients in the studies by McWilliams et al [23,40] or Kroenke et al [42] and He et al [41]. Our sample, therefore, represented patients with a more serious disease spectrum than previously published prevalence studies. A greater functional loss and higher levels of pain have been shown to be associated with a greater incidence of major depression and anxiety [43]. Our patients also were facing the prospect of major surgery and extended rehabilitation, which may have led to the higher rates of generalized anxiety. Given the moderately high prevalence rate of major depression and generalized anxiety disorder and the realities of clinical practice, where time for direct patient contact is limited to a few minutes, it is critical to identify easy-to-assess variables predictive of psychiatric conditions. We identified several variables that clinicians could use to quickly identify patients at risk for major depression or generalized anxiety disorder. The single most important variable associated with a diagnosis of either major depression or generalized anxiety was a self-report of current treatment for depression, anxiety, or stress. These data suggest that the old adage, history is the best predictor of the future, holds true with regard to presence of a psychiatric disorder. If an individual is having emotional turmoil requiring medical or psychological intervention, it is quite likely that coping with disabling knee pain and impending surgery will increase their risk for major depression or generalized anxiety disorder. Another important factor predictive of psychiatric diagnosis was severity of medical comorbidity. Subjects endorsing more medical problems were more likely to have either major depression or generalized anxiety disorder. This is consistent with the work of McWilliams et al [23]. In their large study of communitydwelling adults, individuals with multiple physical problems had the highest rates of psychopathology. Several theories have been proposed for this connection between medical illness and psychiatric disorders. Increasing physical disability disrupts lifestyle and decreases quality of life, raising vulnerability to depression. In addition, iatrogenic properties of medicines used to treat pain disorders may also impact on mood and anxiety levels in these patients. Finally, disabling mood disorders may interfere with an individual's capacity to manage their medical conditions and/or comply with treatment, serving to make their physical illness worse. The question of causation is an interesting one, but we were unable to explore causation because our study was cross sectional. We cannot speculate, therefore, whether the psychiatric problems identified in our patients predated or were a consequence of their knee pain. Two demographic variables emerged as independent predictors of psychiatric diagnosis. Being separated or

6 586 The Journal of Arthroplasty Vol. 25 No. 4 June 2010 Table 5. Multivariable Logistic Regression Model (N = 283) for Prediction of Generalized Anxiety Disorder Using WOMAC Pain as an Independent Variable * 95% CI for OR B SE Wald df Significance OR Lower Upper Self report of Psych treatment Comorbidity Score High school grad or less WOMAC Pain score b Constant b OR indicates odds ratio. * Model parameters shown are raw regression coefficients (B) and standard errors, the Wald statistic with the associated degrees of freedom and significance, and the odds ratio for each variable along with 95% confidence intervals. divorced was associated with presence of major depression. Absence of spousal support has been shown to reduce quality of life [44], life expectancy [45], and adaptation to physical illness [46]. Degeneration of the knee interferes with ambulation, reduces quality of life, and places increasing demand on an individual's social support system. It is therefore not surprising that marital status was related to emotional suffering. Interestingly, the presence of generalized anxiety disorder was more common among less-educated patients. Coping with chronic pain requires physical, emotional, and intellectual resources. Years of education completed is relied upon by psychologists as a proxy for level of intellectual function [47]. An individual's intellectual ability and level of education completed may determine the quality/variety of available coping strategies or the level of environmental stress. The physical dysfunction associated with disabling knee pain may have particular impact on individuals with limited educational attainment. Those individuals completing high school or less may be limited in terms of the jobs they qualify for or their ability to cope with work and life demands as compared with college educated persons. They may, for example, be more likely to be relegated to careers that are heavily physical in nature. Obesity was an independent predictor of depression but not anxiety. Obesity, depression, pain, and reduced functional status have been shown to be associated in multiple studies of patients with arthritis [48,49]. Research examining the association between obesity, anxiety, pain, and poor function among patients with arthritis is less common. One study found a weak relationship between anxiety disorder and obesity in patients with osteoarthritic knee pain, but this relationship was inconsistent depending on the statistical model [50]. We found that WOMAC Pain scores were independently associated with generalized anxiety disorder, but WOMAC Function scores were not. This finding differs from work reported by Kroenke et al [42], who found that both bodily pain and physical function were reduced in a heterogeneous sample of 965 primary care patients with generalized anxiety disorder relative to patients without this disorder. These differences may be due to the fact that we used different covariates and different measures to quantify pain and function or the differences may be due to the samples studied. It is unclear to us why WOMAC Function scores do not explain variation in generalized anxiety status, whereas WOMAC Pain scores were important predictors. We suspect this may be related to the notion that patients scheduled for knee arthroplasty surgery and who have generalized anxiety disorder are more impacted by pain than by functional loss, although this requires further study. Our data suggest that associations between major depression and pain and function are very similar as evidenced by the models presented in Tables 2 and 3. The β coefficients for the 2 models are almost identical, and the variation explained when either WOMAC Pain or Function scores are included in the model are similar. Generalized anxiety disorder, on the other hand, appears to only be preferentially affected by pain but not function. Several limitations of this study should be noted. The study sample was limited to adults scheduled for knee arthroplasty. Therefore, the results of this study may not be generalizable to other pain conditions and to younger or more elderly patients scheduled for knee arthroplasty. Many of the scales relied on in this study are self-report in nature and may be biased by overreporting physical symptoms in patients who have generalized anxiety disorder or major depression. The WOMAC Pain Scale emphasizes the nature of how pain reduces function. It is not a measure specifically evaluating pain sensation intensity, which may explain the high correlation among WOMAC Pain and Function scores. However, these measures are among the most commonly recommended instruments for patients with knee osteoarthritis. Future studies may wish to choose scales that are more specific in assessing pain sensation intensity. Although we had a very small number of patients who did not complete the mental health measures (n = 7 for the depression and panic disorder instruments and n = 12 for the generalized anxiety instrument), these missing data may have influenced the results. Determination of psychiatric diagnosis in our study was made using brief, self-report instruments. Although

7 Depression, General Anxiety Disorder, and Panic Disorder Riddle et al 587 studies examining these scales have demonstrated sound reliability and validity [29,30], this diagnostic method is not the equivalent of a clinical interview. Individuals who are experiencing severe knee pain and resulting loss of function may experience sleep disturbance, social withdrawal, concentration problems, and fatigue. Endorsement of these complaints on the questionnaires used in this study may have increased a subjects' likelihood of being classified with a psychiatric disorder. The high prevalence rates for mood and anxiety disorders in our sample may, in part, reflect the impact of knee-related disability on quality of life. Although symptoms of major depression and generalized anxiety disorder overlap with quality-of-life changes associated with disabling arthritis, the approximate 20% prevalence rate of these disorders in our study is in line with other studies examining prevalence rates of psychiatric disorders in urban general urban medical practice settings [39]. Finally, we had some missing data. The final models in Tables 2, 3, and 5 indicate that sample sizes varied between 283 and 289 patients representing an approximate 7% reduction in sample size. We believe the missing data had little effect on our conclusions, but this loss may have had some effect on the estimates. Despite some limitations, our study contributes to literature examining the association between pain, major depression, and anxiety disorders. Given that a strong association between these disorders has consistently been found across several studies, future studies using more precise assessment of pain intensity and psychiatric diagnosis are clearly warranted and have potential for enhancing our understanding of the relationship between pain, psychiatric disorders, and outcome in this substantial population of patients. With that said, cross sectional findings of this study suggest that inquiring about specific demographic and clinical variables will help clinicians identify those patients at greatest risk for major depression and generalized anxiety disorder. References 1. NIH consensus panel. NIH Consensus Statement on total knee replacement December 8-10, J Bone Joint Surg Am 2004;86-A: Lingard EA, Katz JN, Wright EA, et al. Predicting the outcome of total knee arthroplasty. J Bone Joint Surg Am 2004;86-A: Fortin PR, Clarke AE, Joseph L, et al. 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