Pain in human immunodeficiency virus. Pain and Depression in HIV Illness

Transcription

1 Pain and Depression in HIV Illness SUSAN EVANS, PH.D., STEPHEN FERRANDO, M.D. MARGARET SEWELL, PH.D., KATHY GOGGIN, PH.D. BARUCH FISHMAN, PH.D., JUDITH RABKIN, PH.D., M.P.H. The purpose of this study was to examine the relationship among pain and depression, hopelessness, and quality of life in human immunodeficiency virus (HlV)-infected gay men, taking into account the role of HIV symptoms. One hundred sixty-one HIV gay men were assessed, with 40 men endorsing HIV-related pain. The HIV men with pain had a modal rating of pain within the mild range. They had significantly more advanced disease, more physical and depressive symptoms, and reported less life satisfaction than the men without pain. However, when HIV illness variables are accounted for, the higher depression scores in the men with pain were largely accounted for by somatic rather than cognitive symptoms. While pain is associated with greater physical distress in this cohort of HIV-seropositive gay men, it does not appear to be independently associated with cognitive symptoms of depression. These findings apply to HIV-infected men with mild pain and may not apply to those who experience more severe pain. Nonetheless, these observations highlight the overlap between symptoms of depression and pain and the challenge that clinicians face in assessing patients suffering from pain. (Psychosomatics 1998; 39: ) Received January 21, 1998; revised March 27, 1997; accepted July 9, From the Department of Psychiatry, Cornell University Medical College, New York; and the Aaron Diamond Foundation. Address reprint requests to Dr. Evans, HIV Clinical Research Program, 445 East 68 Street, #3K, New York, NY SUSAN_EVANS@yahoo.com. Copyright 1998 The Academy of Psychosomatic Medicine. Pain in human immunodeficiency virus (HIV)-seropositive (HIV ) persons is widespread and associated with significant psychological and functional impairment. 1 5 Singer et al. 2 studied pain symptoms associated with HIV infection and found an association between the frequency of multiple pains and depressive symptoms. Breitbart et al. 3 examined the medical characteristics of 438 ambulatory AIDS patients and found that over 60% reported frequent or persistent pain, and the on average pain intensity was in the moderate range. The authors found that the presence of pain was significantly associated with number of HIV-related symptoms and more functional impairment, reflecting greater physical debilitation. Pain was associated with interference with mood and enjoyment in life, which increased with the intensity of the pain. The impact of pain and pain intensity on psychological well-being and quality of life was further explored in a subsequent paper. 4 The authors found that the patients with pain had significantly more depressive symptoms, psychological distress, and were more hopeless than those without pain. Larue et al. 5 looked at HIV patients at different stages of disease and found that those patients with significant pain reported lower quality of life than those with no pain and that significant pain had an independent negative impact on the HIV patient s quality of life after 528 PSYCHOSOMATICS

2 Evans et al. adjustment for treatment setting, stage of disease, fatigue, sadness, and depression. Taken together, these studies suggest that pain in HIV disease is associated with depressive symptoms and has a negative effect on quality of life. Nonetheless, the question of comorbidity of pain and depression is confounded by the presence of physical symptoms common to both syndromes, 6,7 such as disrupted sleep patterns, appetite changes, reduced activity, and decreased libido. Also, since depression inventories such as the Beck Depression Inventory and the Hamilton Depression Rating Scale (Ham-D) include a number of somatic items, a question emerges as to whether high scores are related to the number of physical symptoms endorsed vs. cognitive symptoms of depression, such as loss of pleasure and interest in life. Another question is whether HIV-infected patients with pain are physically sicker than those without pain and would therefore score higher on depression inventories that measure both physical and cognitive symptoms. Breitbart, 8 for example, reports that as with cancer, the prevalence of pain increases as disease progresses, with 25% 30% of patients with earlystage HIV reporting pain, increasing to 50% in patients with late-stage HIV illness. McCormack et al., 9 however, found that there did not appear to be a correlation between pain and severity of disease in HlV-infected patients, suggesting that pain in this population is nonspecific to the time course of the disease. Lebovits et al. 10 also found that pain in AIDS patients was not related to disease characteristics such as time since diagnosis. With these two questions in mind, the objective of the present study, conducted in 1996, was to examine the relationship between depression and pain, taking into account the role of HIV symptoms and manifestations. Specifically, the authors sought to determine whether pain was associated with disease progression and, if so, to explore how these factors might contribute to patient s self-report of mood status, feelings of hopelessness, and quality of life. In this context, the aims of the current study were 1) to compare the degree of disease progression and physical manifestations of HIV disease in HIV men with and without pain; 2) to compare levels of depression, hopelessness, and quality of life in HIV men with and without pain; and 3) to determine whether men with and without pain differ on measures of depressed mood, hopelessness, and quality of life after controlling for the effects of physical symptoms. METHODS Sample The subjects were HIV men self identified as gay who agreed to participate in a longitudinal cohort study of psychological adaptation to HIV illness. These assessments were conducted at the second semiannual visit. Subjects were recruited by posting notices at community-based acquired immunodeficiency syndrome (AIDS) organizations, clinics, and gay-community bulletin boards. Word of mouth was a significant source of recruitment as well. Interviewers All interviewers were postdoctoral fellows in a National Institute of Mental Health sponsored HIV research training program who had extensive prior clinical and diagnostic assessment experience. Medical information was elicited by clinicians under the supervision of a physician who worked in the hospital HIV/AIDS clinic (SF). Laboratory test results were reviewed by him before being sent to the subjects, with a cover letter noting any medically significant findings that the subject should notify his physician about. Procedure Each participant was seen for about 3 hours, during which self-rating scales and a clinicianadministered interview were completed. The participant then went to Metpath-Corning (now Quest), a widely used regional commercial laboratory, for blood tests. All participants gave VOLUME 39 NUMBER 6 NOVEMBER DECEMBER

3 Pain and Depression in HIV written informed consent and were paid $30 for the visit. Measures T-cell Lymphocyte Subsets. Assays to determine number and percent of CD4 and CD8 T-cells were performed. CD4 cell count is one component of the 1993 Centers for Disease Control and Prevention (CDC) criteria for AIDSdefining conditions, with values less than 200 cells/cu mm constituting such a condition. Medical Symptom Checklist. This is a refinement of the HIV symptom checklists used earlier to characterize HIV cohorts at Cornell 11 and Columbia. 12 The checklist consists of 14 signs and symptoms commonly but not exclusively associated with HIV infection, such as night sweats, shortness of breath, and fever. These symptoms are scored for two time frames: 1) present or absent today, and 2) present or absent for 1 month or more in the past 6 months. Pain, fatigue, and weight loss were omitted from the checklist to minimize multicollinearity among variables. Opportunistic Infections (OI). Based on medical history, the number of past or present OIs, according to CDC criteria, 13 was recorded for each subject. Chalder Fatigue Scale (CFS). 14 This is a selfreport scale that was developed to assess severity of fatigue in a general medical population. Nine items ask whether, in the past week, subjects have 1) felt tired; 2) needed rest during the day; 3) felt sleepy or drowsy; 4) found it difficult to start doing things; 5) had enough energy; 6) had enough strength in his muscles; 7) felt weak; 8) felt that fatigue interferes with ability to breathe, bathe, feed, or dress; and 9) felt that fatigue interferes with ability to engage in enjoyable activities. Response options are rated on a 5-point scale: never ( 1), rarely ( 2), sometimes ( 3), often ( 4), and always ( 5). Items are summed to obtain a total severity score (range: 9 45). Beck Depression Inventory (BDI). 15 The BDI is a self-report scale that measures symptoms, affects, and thoughts characteristic of depression, and each of 21 items is scored from absent (0) to severe (3). Each item represents a depressive symptom and consists of four statements, with gradations of severity for each particular category. A score of 13 or above has been recommended for research purposes as the cutoff to indicate significant depressive symptomatology. 16 Beck Hopelessness Scale (BHS). 17 This is a 20-item measure in true false format, with half scored in reverse. Scores of 0 3 indicate a lack of hopelessness, 4 8 represents mild hopelessness, 9 12 represents moderate hopelessness, and scores over 12 indicate severe hopelessness. Sample item is I look forward to the future with hope and enthusiasm. Endicott Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). 18 This short version is a self-rating scale inquiring about satisfaction during the past 2 weeks, with 14 separate areas of functioning (e.g., physical health, mood, social relationships, sexual drive and interest, living/housing situation) and a global question about overall life satisfaction. The response format ranges from 1 very poor to 5 very good. Total score is the sum of items 1 14 (range: 14 70) and the global rating 1 5. Memorial Pain Assessment Card (MPAC). 19 This is a visual-analogue tool measuring pain along a 100-mm line and across 3 dimensions (pain intensity, relief, and mood). The patients were asked to 1) place a mark along the line that best describes the severity of pain at the present time (0 no pain to 100 the worst pain); 2) circle the word that best describes their pain ( no pain, just noticeable, weak, mild, moderate, strong, severe, and excruciating ); 3) place a mark along the line that best describes the relief they are currently experiencing from the pain at the moment (0 no relief to 100 complete relief); and 4) place a mark 530 PSYCHOSOMATICS

4 Evans et al. along the line that best describes their mood at the present time (0 worst mood to 100 the best mood). The MPAC, used widely in trials of analgesic drugs, is a validated and rapid evaluation of the multidimensional aspects of pain. Statistical Analyses T-tests for unequal N s were used to compare means of continuously scored variables between the two groups, that is, the HIV men with pain and those without pain. To avoid confounding somatic symptoms attributable to depression and HIV, separate analyses were conducted for the 15 cognitive/affective symptoms of depression and the 6 somatic symptoms of the BDI. Two separate analyses were conducted on the Q-LES-Q, including 1 on the 14 domains of functioning and the other on overall life satisfaction. Analysis of covariance was conducted between the pain and no pain groups. Covariates included markers of disease progression, CD4 count, and the medical symptom checklist, which significantly differentiated the pain and no pain groups. Since the CD4 count curve was positively skewed in this sample, a transformation to 0.4 power was conducted. Perniger et al. 20 have recommended this procedure as the best transformation when predicting clinical outcome. In our sample, this transformation demonstrated a normally distributed curve (Kolmogorov Smirnov Z 0.86, P 0.44). RESULTS Sample Demographic Characteristics. Data were collected from 161 men. The mean age was 40 (standard deviation [SD] 7.6, range: 26 66). Fifty-nine percent were White, 19% African American, and 19% Hispanic. The remaining 3% included Asian, Native American, and those of multiracial background. This was a welleducated sample of men, with 86% having had some post-high school academic or vocational education. Medical Characteristics. The mean CD4 cell count for the entire group was 221 cells/cu mm (SD 209); the mean number of physical symptoms over the previous 6 months was 2.1 (SD 2.0, range: 0 9); and the mean fatigue score was 23.8 (SD 7.3, range: 9 45), which is indicative of moderate fatigue. Forty percent of the group had experienced at least one OI and/or had a CD4 cell count 200 cells/cu mm, thus meeting the CDC criteria for an AIDS diagnosis. Prevalence of Pain. Forty of the 161 men reported HIV-related pain and were administered the MPAC. The mean pain score at the time of interview was 25.4 mm (SD 22.3, range: 0 89), which is indicative of mild pain. The men also reported, on average, moderate relief from pain at the moment of interview (58.9 mm, SD 34.2, range: 2 99) and moderately good mood (62.2 mm, SD 26.3, range: 2 99). The mean descriptor of the pain was in the mild range. Correlates of Pain and Pain Intensity. As shown in Table 1, for the 40 men with pain, pain as measured by the visual-analogue scale was not significantly correlated with physical measures associated with HIV illness, including fatigue, CD4 count, medical symptoms, the measures of depression (BDI), hopelessness (BHS), and quality of life (Q-LES-Q). Pain intensity was also not significantly correlated with fatigue, CD4 count, medical symptoms, BHS, and Q-LES-Q but was significantly associated with the BDI. The physical measures associated with HIV infection, including fatigue, CD4 count, and medical symptoms, were intercorrelated. #1: Differences Between Patients With Pain vs. Those Without Pain on Markers of Disease Progression. As shown in Table 2, the pain subjects had significantly lower CD4 counts and reported more physical symptoms and fatigue over VOLUME 39 NUMBER 6 NOVEMBER DECEMBER

5 Pain and Depression in HIV the previous 6 months than the men without pain. The pain patients also reported more OIs than those without pain. There were no demographic differences between the groups. #2: Do Patients With Pain Report More Depression, Hopelessness, and Poorer Quality of Life Than Patients Without Pain? Table 3 shows the mean differences between the pain and no pain groups on the BDI, BHS, and Q-LES-Q. Results demonstrate that the patients with pain had significantly higher scores on both the cognitive/affective and somatic subscales of the BDI as well as total score BDI than those without pain, indicating that the men with pain were significantly more depressed. The mean score in the pain group was in the mildly depressed range. In terms of quality of life, the patients with pain reported less satisfaction in several domains, such as their physical health, sexual life, and family and social relationships. They were not significantly different from the men without pain in terms of their overall rating of satisfaction with life, nor did the former report more feelings of hopelessness than the men without pain. #3: Differences in Depression and Life Satisfaction Between the Pain and No Pain Groups, Controlling for Differences in Disease Progression. To further elucidate the relationship between pain, depression, hopelessness, and quality of life taking into account the role of disease progression and number of physical symptoms of pain an analysis of covariance was conducted between the men with and without pain on the BDI, its subscales, BHS, and Q-LES-Q. Covariates included CD4 count and TABLE 1. Correlates of pain and pain intensity (N 40) Pain Pain Intensity Fatigue CD4 Medical Symptoms BDI BHS Q-LES-Q Pain 1.0*** 0.67** Pain intensity * Fatigue 0.18* 0.38** 0.56** 0.35** 0.60** CD4 0.28** 0.27** 0.24* 0.15 Medical symptoms 0.37** ** BDI 0.68** 0.70** BHS 0.61** Note: BDI Beck Depression Inventory; BHS Beck Hopelessness Scale; Q-LES-Q Endicott Quality of Life Enjoyment and Satisfaction Questionnaire. *P 0.05, **P TABLE 2. Demographic and medical characteristics No Pain (N 121) Pain (N 40) Test Statistic Mean age, years NS At least some college, % NS White, % NS CD4, mean SD t 1.96* No. of symptoms past 6 months, mean SD t 3.7*** History of opportunistic infections, % v 2 5.2* Fatigue t 2.94** Note: NS not significant. *P 0.05, **P 0.01, ***P PSYCHOSOMATICS

6 Evans et al. TABLE 3. Measure T-test for equality of unequal N s between no pain and pain groups No Pain (N 121) Mean SD Pain (N 40) t P BDI total BDI (cognitive) BDI (somatic) BHS Q-LES-Q (14 domains) Q-LES-Q (overall satisfaction) Note: BDI Beck Depression Inventory; BHS Beck Hopelessness Scale; Q-LES-Q Endicott Quality of Life Enjoyment and Satisfaction Questionnaire. medical symptoms associated with HIV disease. Fatigue was excluded as a covariate because it is often a symptom of depression. Results of this analysis, shown in Table 4, indicate that the patients with and without pain remain significantly different in terms of their total BDI and somatic subscale scores but are no longer distinguished from one another on the BDI cognitive subscale. The men with pain continue to endorse less satisfaction in a variety of domains representing quality of life but are no different from the men without pain with regard to the overall life satisfaction and hope for the future. DISCUSSION TABLE 4. Measure Analysis of covariance between no pain and pain groups, controlling for disease progression F Significance of F BDI total BDI cognitive (NS) BDI somatic BHS (NS) Q-LES-Q (14 domains) Q-LES-Q (overall satisfaction) (NS) Note: Covariates: CD4 count transformed to power of 0.4, medical symptom checklist. BDI Beck Depression Inventory; BHS Beck Hopelessness Scale; Q- LES-Q Endicott Quality of Life Enjoyment and Satisfaction Questionnaire; NS not significant. Several interesting findings emerge from this study. First, the men with pain (even at a mild level) demonstrated increased evidence of disease and reported more physical symptoms than the men without pain. This finding supports Breitbart et al. s 3 observations of ambulatory AIDS patients, in whom the presence of pain was significantly associated with physical symptoms and greater physical debilitation. Unlike the present study, however, Brietbart et al. did not find an association between the presence of pain and CD4 cell count. Our findings of increased depressive symptoms in the patients with mild pain appear to extend those of Rosenfeld et al., 4 who found that pain was associated with more depressive symptoms and psychological distress. Our study controls for medical symptoms of HIV illness and CD4 cell count differentiated the patients with and without pain. Our study suggests that even pain of mild intensity is associated with greater physical distress and a diminution of satisfaction across domains such as physical health and sexual drive and interest. However, when physical symptoms are accounted for, the patients with mild pain do not report more cognitive symptoms of depression, such as loss of pleasure, feelings of guilt, and worthlessness, nor do they feel more hopeless than those patients without pain. The patients with pain were no different from the patients without pain in their overall rating of life satisfaction. VOLUME 39 NUMBER 6 NOVEMBER DECEMBER

7 Pain and Depression in HIV Several limitations of the present study should be noted. Since this study grew out of work originated in 1987 by Perry et al. 11 examining the psychological impact of HIV illness, whose subjects were predominantly gay men, our sample is also limited to this population. Since the demographics of the HIV/AIDS epidemic have shifted since then, this sample is not representative of the entire population of HIV patients in Conceivably, gay men may use medical care more often and get better treatment for pain. Another possibility is that intravenous drug users in recovery may be less likely be offered or accept pain medication. In fact, our results of mild pain in this cohort supports this possibility, since Breitbart et al. s study, 3 which included intravenous drug users, reported that the average pain was in the moderate level. Second, these findings apply to HIVinfected subjects with pain intensity in the mild range. Further study is needed to determine the relationship of distress and depressive symptoms in those with severe pain. These observations highlight the overlap between symptoms of depression and pain and the challenge that clinicians face in assessing patients experiencing pain. Distinguishing between somatic vs. cognitive and affective symptoms of depression may be useful in clarifying the mental state of patients with HIV. Our results suggest that despite the greater physical distress experienced by HIV patients with mild pain, these individuals continue to remain hopeful and maintain an interest in, and enthusiasm for, life. This study was partially supported by a grant from the National Institute of Mental Health (Grant No. 5 RO1 MH42277) to Dr. Rabkin. The funding for this research was originally awarded to the late Samuel W. Perry, M.D., and this work is a legacy to his commitment to research on the psychiatric aspects of HIV/AIDS. The authors also thank Scott Cohen, Nancy Kunz, Zohn Rosen, and Dean Haglin for their contributions, as well as the study participants. References 1. Breitbart W: Pain management in the patient with AIDS. Pain Management 1994; 2: Singer EJ, Zorilla C, Fahy-Charnldon B, et al: Painful symptoms reported by ambulatory HlV-infected men in a longitudinal study. Pain 1993; 54: Breitbart W, McDonald MV, Rosenfeld B, et al: Pain in ambulatory AIDS patients. I: Pain characteristics and medical correlates. Pain 1996; 68: Rosenfeld B, Breitbart W, McDonald MV, et al: Pain in ambulatory AIDS patients. II: Impact of pain on psychological functioning and quality of life. Pain 1996; 68: Larue F, Fontaine A, Colleau SM: Underestimation and undertreatment of pain in HIV disease: a multicentre study. BMJ 1997; 314: Parham-Vetter PC: Depression and chronic pain: a review. Primary Psychiatry, May 1996, pp Perkins DO, Leserman J, Stern RA, et al: Somatic symptoms and HIV infection: relationship to depressive symptoms and indicators of HIV disease. Am J Psychiatry 1995; 152: Breitbart W: Pain management and psychosocial issues in HIV and AIDS. American Journal of Hospice and Palliative Care 1996; 13: McCormack J, Li R, Zarowny D, et al: Inadequate treatment of pain in ambulatory HIV patients. Clin J Pain 1993; 9: Lebovits AH, Smith G, Maignan M, et al: Pain in hospitalized patients with AIDS: analgesic and psychotropic medications. Clin J Pain 1994; 10: Perry SW, Jacobsberg L, Card C, et al: Severity of psychiatric symptoms after HIV testing. Am J Psychiatry 1993; 151: Rabkin JG, Williams JBW, Remien RH, et al: Depression, distress, lymphocyte subsets, and HIV symptoms on two occasions in HIV-positive homosexual men. Arch Gen Psychiatry 1991; 48: Centers for Disease Control and Prevention: 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. Morb Mortal Wkly Rep 1992; 41: Chalder T, Berelowitz G, Pawlkowska T, et al: Development of a fatigue scale. J Psychosom Res 1993; 37: Beck A, Ward CH, Mendelson M, et al: An inventory for measuring depression. Arch Gen Psychiatry 1961; 4: Beck AT, Beamsderfer A: Assessment of depression: the depression inventory. Mod Probl Pharmacopsychiatry 1974; 7: PSYCHOSOMATICS

8 Evans et al. 17. Beck AT, Weissman A, Lester D, et al: The measurement of pessimism: the Hopelessness Scale. J Consult Clin Psychol 1974; 42: Endicott J, Nee J, Harrison W, et al: The Quality of Life and Enjoyment Satisfaction Questionnaire. Psychopharmacol Bull 1993; 2: Fishman B, Pasternak S, Wallenstein SL: The Memorial Pain Assessment Card: a valid instrument for the evaluation of cancer pain. Cancer 1987; 60: Perniger TV, Yerly S, Perrin L: Transforming laboratory test results to improve clinical outcome predictions in HIV patients. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 17: VOLUME 39 NUMBER 6 NOVEMBER DECEMBER