Psychosomatics 44:244-248, June 2003
© 2003 The Academy of Psychosomatic Medicine
Somatic Symptoms for Diagnosing Major Depression in Cancer Patients
Tatsuo Akechi, M.D., Ph.D.,
Tomohito Nakano, M.D.,
Nobuya Akizuki, M.D.,
Masako Okamura, M.D.,
Keiko Sakuma, M.D.,
Tatsuro Nakanishi, M.D.,
Eisho Yoshikawa, M.D., and
Yosuke Uchitomi, M.D., Ph.D.
Received May 14, 2002; revision received Sept. 20, 2002; accepted Oct. 18, 2002. From the Psycho-Oncology Division, National Cancer Center Research Institute East; the Psychiatry Divisions of the National Cancer Center Hospital (Tsukiji, Japan) and the National Cancer Center Hospital East (Kashiwa, Japan); and the Department of Psychiatry, Kashiwa Hospital, Jikei Medical University, Kashiwa, Japan. Address reprint requests to Dr. Uchitomi, Psycho-Oncology Division, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan; yuchitom{at}east.ncc.go.jp (e-mail).
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ABSTRACT
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Diagnosing depression in cancer patients has been challenging because the diagnostic criteria include somatic symptoms frequently attributed to the cancer itself or its treatment. However, few studies have explored how to appropriately deal with individual somatic symptoms. The authors used data from 220 cancer patients with major depression to examine the intercorrelations among the DSM-IV somatic and nonsomatic symptom criteria as well as whether the presence of an individual somatic symptom could discriminate the severity of major depression. Appetite changes and a diminished ability to think were positively associated with anhedonia. Sleep disturbance and fatigue were not significantly associated with nonsomatic symptoms. These associations were consistent after adjusting for physical functioning and pain. Only patients with appetite changes showed a higher severity of depression. These results suggest that individual somatic symptoms differ in nature and that appetite-related symptoms and a diminished ability to think may be useful for diagnosing depression in cancer patients, whereas sleep disturbances and fatigue may not be as useful.
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INTRODUCTION
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Major depression is among the most widely recognized psychiatric disorders in cancer patients.1 It not only produces serious suffering2 but also worsens quality of life,3 reduces compliance with anticancer treatment,4 can lead to suicide,5 is a psychological burden on the family,6 and prolongs hospitalization.7 Thus, early detection and appropriate management of major depression in cancer patients are crucial.
However, diagnosing major depression in cancer patients has been challenging because the diagnostic criteria for major depression, established in DSM-IV, include a number of signs and "somatic symptoms" frequently attributed to the cancer itself (e.g., appetite loss, weight loss, insomnia, fatigue, loss of energy, and diminished ability to think or concentrate) or to anticancer treatments such as chemotherapy and radiotherapy.1 Although the original DSM-IV criteria exclude symptoms that are clearly and fully attributable to the general medical condition (etiologic approach), a differential diagnosis is often difficult or even impossible.8 Some investigators have attempted to assess the usefulness of several biological markers for diagnosing major depression in cancer patients, including the hypothalamic-pituitary-adrenal axis (dexamethasone suppression test),9 the hypothalamic-pituitary-thyroid axis (TRH stimulation test),9,10 and serotonin-induced platelet calcium mobilization.11 However, none of these markers have proven definitive. As another strategy for resolving this diagnostic issue, several conceptual approaches have been proposed, such as inclusive (symptoms are counted whether or not they might be attributable to cancer), substitute (nonsomatic symptoms are substituted with somatic symptoms), and exclusive (somatic symptoms are deleted from the diagnostic criteria) approaches.12 Although the inclusive approach is generally recommended, especially in a clinical setting, for diagnosing major depression in physically ill patients to avoid underestimating depression,13 standard methods for the diagnosis of major depression have not been established.8 Thus, while appropriately dealing with somatic symptoms is a key issue in the diagnosis of major depression in cancer patients, only a few studies have explored how to appropriately deal with individual somatic symptoms.
The objective of this preliminary study was to clarify the somatic symptoms among the DSM-IV criteria for major depression that significantly contributed to a diagnosis of major depression by examining intercorrelations among somatic and other symptoms. We also evaluated the use of somatic symptoms to discriminate the severity of major depression by using data from cancer patients with major depression who had been referred to our psychiatric departments.
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METHOD
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All psychiatric consultations referred to the Psychiatry Divisions at National Cancer Center Hospital and National Cancer Center Hospital East in Japan between 1996 and 1999 were reviewed. A computerized database was used to identify patients with major depression. The database included demographic factors, medical factors such as performance status and pain, and psychiatric diagnoses based on DSM-IV criteria. Performance status, as defined by the Eastern Cooperative Oncology Group criteria, is an objective index of a patient's physical functioning, ranging from 0 (no symptoms) to 4 (bedridden). To assess pain, the psychiatrists directly asked the patients about pain at the time of their first interview, and pain was evaluated as follows: absent, mild, tolerable, or intolerable. A diagnosis of major depression (employing the inclusive approach) was made by using a structured clinical interview based on the DSM-IV criteria. When a criterion was assessed as absent or subthreshold, it was entered as absent (rated as 0) in the database; when assessed as present, it was entered as such (rated as 1). Only data from patients diagnosed as having major depression were extracted from the database. Since this was a retrospective study using data obtained during clinical practice, informed consent and institutional review board approval were not obtained.
Spearman's rank correlation test was used to examine the intercorrelations between each somatic symptom and other nonsomatic items of the inclusive DSM-IV criteria. A logistic regression analysis (dependent variable: nonsomatic symptom; independent variable: somatic symptom) was also conducted to examine intercorrelations between these items after adjusting for physical functioning and pain. In these analyses, to control type I error rates, the level of significance was determined by dividing the standard significance level (0.05) by the number of tests performed (Bonferroni correction). Consequently, the significance level was set at 0.005, since 10 tests were conducted in each analysis. In addition, a Wilcoxon two-sample test was conducted to examine whether the presence of each somatic symptom could be used to discriminate the severity of major depression. In this study, the severity of depression was estimated by using the number of nonsomatic DSM-IV criteria present.
All reported p values are two-tailed. All data analyses were conducted using SAS statistical software (SAS Institute Inc., 2001).
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RESULTS
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A total of 1,721 cancer patients were referred during the study period. Of that number, 220 (12.8%) were diagnosed as having major depression according to the inclusive criteria. Only 1.8% (N=4) of the depressed patients had psychotic features. The mean age of the patients was 58 years (SD=12, median=57, range=17–85). Other patient characteristics are given in Table 1.
Regarding the significant associations between each somatic symptom and the other criteria, weight loss or appetite change was positively associated with a diminished interest or pleasure (r=0.19, df=218, p=0.005). Insomnia or hypersomnia and fatigue were not significantly associated with any other items. A diminished ability to think or concentrate was positively associated with a diminished interest or pleasure (r=0.22, df=218, p=0.001). The results of the logistic regression analyses demonstrated that weight loss or appetite change and a diminished ability to think or concentrate were positively associated with a diminished interest or pleasure after adjusting for possible physical confounders (Table 2).
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TABLE 2. Multivariate Logistic Regression Analysis of the Intercorrelations Between Nonsomatic Depressive Symptoms (dependent variables) and Somatic Depressive Symptoms (independent variables) in Cancer Patients With Major Depression (N=220) After Adjustment for Physical Functioninga and Painb
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Among the somatic symptoms, patients with weight loss or appetite change showed a significantly higher severity of major depression than those without this symptom (z=–3.00, p=0.003), while patients with the other three somatic symptoms did not (sleep disturbance: z=–1.08, p=0.28; fatigue: z=1.50, p=0.13; diminished ability to think: z=–1.52, p=0.13).
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DISCUSSION
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Our findings suggest that individual somatic symptoms differ in nature and may occupy a specific position regarding the diagnosis of major depression in cancer patients.
Several previous studies have indicated that eating-related symptoms may not be useful for diagnosing depression among physically ill patients because these symptoms are also common with physical illness itself.14–16 However, our results suggest that among somatic symptoms, weight loss or appetite change is positively associated with one of the core symptoms of major depression (anhedonia), even after adjusting for physical functioning and pain, and can be used to discriminate the severity of major depression, as defined by the number of nonsomatic symptoms experienced by the patient. This suggests that even with the application of an inclusive approach to diagnosing major depression in cancer patients, weight loss or appetite change may be a useful item. A study conducted by Passik et al.17 explored the factor structure of depressive symptoms with the Zung Self-Rating Depression Scale in ambulatory cancer patients. In that study, a four-factor solution emerged that consisted of a cognitive symptom factor, a manifest depressed mood factor, an eating-related somatic factor, and a non-eating-related somatic factor. Thus, it showed eating-related symptoms to be an independent factor, distinguishable from other somatic symptoms. The results of both studies suggest that eating-related somatic symptoms have a unique nature in cancer patients, i.e., they are different from other somatic symptoms and may facilitate the diagnosis of major depression in cancer patients.
Regarding a diminished ability to think, this symptom has not been considered useful for the diagnosis of depression among physically ill patients,12,18 although several papers have indicated that similar symptoms, such as difficulty with decisions and indecisiveness, may be useful.14,15 The findings of the present study indicated that a diminished ability to think is independently associated with anhedonia, even after adjusting for the effects of physical functioning and pain. However, this symptom could not be used to discriminate the severity of major depression. Cull et al.19 investigated the factors influencing cancer patients' complaints of concentration and memory difficulties and found that these complaints were significantly associated with the presence of depression, although they were not associated with objective neuropsychometric test results for concentration and memory. These previous findings and the results of the present study suggest that a diminished ability to think may be helpful for the diagnosis of major depression in cancer patients.
Regarding sleep disturbances, diagnostic usefulness of this symptom seems to be controversial; several studies have suggested its potential usefulness for the diagnosis of depression in physically ill patients, including those with cancer,14–16 whereas others have not.17,18 However, we found that neither insomnia nor hypersomnia contributed to the diagnosis of major depression in cancer patients because this symptom was not significantly associated with core symptoms (such as depressed mood and anhedonia) and also could not be used to discriminate the severity of major depression. Thus, our findings suggest that this criterion is not helpful for the diagnosis of depression in cancer patients. However, the aforementioned study conducted by Passik et al.17 indicated that sleep-related symptoms do not load on any factors, including somatic factors, which suggests that this symptom may have a unique nature. Thus, a well-designed study is needed to clarify the usefulness of sleep-related criteria in the diagnosis of major depression in cancer patients.
Previous studies have consistently indicated that fatigue is not a useful item for the diagnosis of depression in physically ill patients.14,15,18 We also found that fatigue or a loss of energy may actually confuse the diagnosis of major depression in cancer patients because this somatic symptom was not significantly associated with core symptoms, such as depressed mood and anhedonia, and could also not be used to discriminate the severity of major depression. Thus, a fatigue criterion does not seem to be helpful for the diagnosis of major depression in cancer patients.
This preliminary retrospective study has several limitations. Since only referred cancer patients diagnosed with major depression were used as subjects, our findings cannot be generalized to describe all depressive cancer patients. Another important problem is the inability to verify the reliability of the interviews used to arrive at a diagnosis of major depression. In addition, the referred patient sample may have been influenced by a physician bias. The classification of major depression severity may also be problematic, since severity is usually decided by considering the number and intensity of symptoms, including both nonsomatic and somatic symptoms.
In conclusion, individual somatic symptoms differ in nature and should be considered separately when diagnosing a cancer patient with major depression. Some symptoms, such as those related to appetite and a diminished ability to think, may be useful for the diagnosis of major depression in cancer patients, while others, such as sleep disturbances and fatigue, may not be as useful.
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ACKNOWLEDGMENTS
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Supported in part by a Grant-in-Aid for Medical Frontier Strategy Research from the Japanese Ministry of Labor, Health and Welfare. The authors thank Tomoyuki Hanaoka, M.D., Ph.D., for his advice regarding the statistical analysis, and Ms. Ryoko Katayama and Ms. Yurie Sugihara, B.A., for their research assistance.
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ABSTRACT
INTRODUCTION
