Japanese Journal of Clinical Oncology, 2016, 46(1) 71–77 doi: 10.1093/jjco/hyv169 Advance Access Publication Date: 19 November 2015 Original Article
Original Article
Prevalence and predictive factors of depression and anxiety in patients with pancreatic cancer: a longitudinal study Nobuya Akizuki1, Ken Shimizu2,*, Mariko Asai3, Tomohito Nakano4, Takuji Okusaka5, Kazuaki Shimada6, Hironobu Inoguchi2, Masatoshi Inagaki7, Maiko Fujimori8, Tatsuo Akechi9,10, and Yosuke Uchitomi11 1
Psycho-Oncology Division, Chiba Cancer Center, Chiba, 2Department of Psycho-Oncology, National Cancer Center Hospital, Tokyo, 3Graduate School of Clinical Psychology, Teikyo Heisei University, Chiba, 4Psychiatry Division, Kitasato University Kitasato Institute Hospital, Tokyo, 5Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, 6Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, 7Department of Neuropsychiatry, Okayama University Hospital, Okayama, 8Section of Medical Research for Suicide, Center for Suicide Prevention, National Institute of Mental Health, National Center for Neurology & Psychiatry, Tokyo, 9Division of Palliative Care and Psycho-oncology, Nagoya City University Hospital, Aichi, 10 Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Aichi, and 11Innovation Center for Supportive, Palliative and Psychosocial Care, National Cancer Center, Tokyo, Japan *For reprints and all correspondence: Ken Shimizu, Department of Psycho-oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. E-mail;
[email protected] Received 6 July 2015; Accepted 21 October 2015
Abstract Objective: It is known that depression and anxiety occur more frequently in pancreatic cancer patients than in those with other malignancies. However, few studies have assessed depression and anxiety using reliable psychiatric diagnostic tools. The purpose of this study was to determine the prevalence of depression and anxiety among pancreatic cancer patients before and 1 month after the start of anticancer treatment using reliable psychiatric diagnostic tools, and to identify factors that predict their occurrence. Methods: Pancreatic cancer patients were consecutively recruited. Structured clinical interviews were used to determine the presence of affective disorders, anxiety disorders and adjustment disorders. Baseline interviews were performed prior to initiation of anticancer treatment, while follow-up interviews were performed 1 month after treatment was started. Medical, demographic and psychosocial backgrounds were also assessed as predictive factors. Results: One hundred and ten patients participated in the baseline interview and 91 in the follow-up interview. Depression and anxiety were observed in 15 patients (13.6%) at the baseline, and 15 patients (16.5%) at the follow-up. Lack of confidants was associated with depression and anxiety at the baseline. At the baseline, sadness, lower Karnofsky Performance Status and prior experience with the death of a family member due to cancer predicted newly diagnosed depression and anxiety at the follow-up. Conclusion: A considerable percentage of pancreatic cancer patients experienced depression and anxiety. Multidimensional psychosocial predictive factors were found and optimal psychological care should incorporate early detection of sadness. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email:
[email protected]
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Psychiatric problem in pancreatic cancer patients
Key words: pancreatic neoplasms, depression, anxiety, prevalence
Introduction Depression and anxiety are common psychiatric symptoms in cancer patients (1,2). Depression and anxiety have a number of effects on cancer patients, including reduced quality of life (3), altered decisionmaking regarding treatment (4), increased desire for death (5) and a greater rate of suicide (6,7). Among various malignant diseases, pancreatic cancer is believed to have one of the highest rates of concomitant depressive disorders (1,8,9). Previous studies reported that the prevalence of depression and anxiety in patients with pancreatic cancer ranged from 10 to 76% (10–15), but few used reliable diagnostic tools. In patients with pancreatic cancer, depression and anxiety have been reported to precede somatic symptoms. Two prospective studies reported that psychiatric symptoms were the first indication of pancreatic cancer in 50% of patients (10,13). As a result, some researchers have theorized that depression and anxiety in this population may be linked to tumor-induced changes in neuroendocrine or acid–base systems (13). However, these studies used relatively small samples and lacked data on the frequency with which depression and anxiety preceded physical symptoms. Despite the development of new anticancer treatments, the overall median survival of patients with pancreatic cancer is 3–5 months, with a 12-month survival rate of 10% (16,17). Once identified, treatment of depression often takes at least 2 weeks or longer (9). Given patients’ limited life expectancy and the time required for antidepressant treatment, prevention of depression is as important as early detection. Identifying the predictive factors of depression and anxiety in pancreatic cancer patients should lead to appropriate prevention and management, however there has been little information as to why some pancreatic cancer patients suffer from depression and anxiety and others do not. The primary purpose of the present study was to determine the prevalence of depression and anxiety among pancreatic cancer patients. The secondary purposes were to clarify the frequency with which depression and anxiety preceded physical symptoms and to identify the predict factors of depression and anxiety. A strong point of this study in comparison with previous studies was the use of reliable diagnostic tools and a longitudinal study design.
Patients and methods Patients Consecutive, newly diagnosed inpatients with pancreatic cancer were recruited at the National Cancer Center Hospital (NCCH; Tokyo, Japan) between August 2003 and May 2004. The eligibility criteria for recruitment were: (i) age 18 years or older, (ii) clinical diagnosis of pancreatic cancer, (iii) awareness of the pancreatic cancer diagnosis, (iv) no history of anti-pancreatic cancer treatment, (v) ability to speak and read Japanese (vi) not being too ill to complete the questionnaires and participate in an interview taking at least 30 min and (vii) the absence of cognitive impairment. For the clinical diagnosis criterion, computed tomography or magnetic resonance imaging of the abdomen was required. For each case, the ‘not too ill’ criterion was discussed by oncologists and investigators to avoid biased judgment. Patients who were subsequently proven to have non-malignant tumors after biopsy or surgery were excluded.
This study was approved by the institutional review board and the Ethics Committee of the National Cancer Center of Japan and was conducted in accordance with the Helsinki Declaration. Written informed consent was obtained from each subject before the start of the study.
Study procedures Patients who consented to participate in the study were interviewed and asked to fill out the questionnaire before starting their first pancreatic cancer treatment (baseline). One month after this treatment was begun, study investigators discussed the eligibility criteria with the attending oncologist, primarily the criterion concerning the patient being too physically ill. If the patient was determined to be eligible, they were interviewed and asked to complete the questionnaire again (follow-up). Patients judged to be too physically ill were subsequently observed and assessed concerning their psychological problem when possible. Baseline assessments were performed on inpatients only, but follow-up assessments included both inpatients and outpatients. For no missing value existed in all patients’ data, the researchers checked the questionnaire and asked to fill out the blank if any at baseline and follow up assessment (Table 1).
Assessment of depression and anxiety The subjects were assessed for the presence of depression and anxiety by a trained psychiatrist using the Structured Clinical Interview for DSM-III-R (SCID) (18) at the time they were admitted to the NCCH for anticancer treatment (baseline) and again at least 1 month after anticancer treatment was started (follow-up). The SCID modules used were those evaluating affective disorders (present and past history of major depressive disorder and dysthymic disorder), anxiety disorders ( panic disorder, specific phobia, social phobia, obsessive-compulsive disorder, generalized anxiety disorder, posttraumatic stress disorder and acute stress disorder) and adjustment disorders. For the posttraumatic stress disorder and acute stress disorder modules, the authors translated the original Structured Clinical Interview for DSM-IV into Japanese (19), because these two modules were not included in the Structured Clinical Interview for DSM-III-R. Patients were asked at the baseline interview to identify the time of onset of depression and anxiety, to allow comparison with the onset of the first somatic symptoms of pancreatic cancer that caused participants to consult a doctor. The reliability of the interview ratings was assessed based on the concordance rate with the SCID conducted by an independent trained clinical psychologist in 39 cases. Kappa coefficients were 0.76 for any psychiatric diagnosis, 0.79 for major depression and 0.69 for adjustment disorders.
The onset time of the first physical symptoms of pancreatic cancer The onset time of the first physical symptoms were assessed at the baseline by semi-structured interview. We asked the subjects ‘When the first symptoms of pancreatic cancer that caused to consult a doctor did appear?’
Predictive factors of depression and anxiety Demographic and biomedical factors were obtained from patients’ medical charts; these included age, sex, clinical radiographic staging
Jpn J Clin Oncol, 2016, Vol. 46, No. 1 Table 1. Characteristics of pancreatic cancer patients at the baseline (n = 110) Characteristics
n
Age (mean ± SD, range)
61.7 ± 9.8 (27–90) years 68 (61.8)
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0 to 10 (24). We used the 13-symptom severity scales with higher symptom-scale scores indicating more severe symptoms.
(%)
Sample size estimation Sex (male) Medical characteristics Clinical stage Resectable Locally advanced Metastatic Tumor location Head Body and tail Diffuse Histology Exocrine Endocrine Carcinoma PTCD ( present) KPS (mean ± SD, range) Alcohol drinking (current drinker) Smoking (current smoker) Comorbid physical illness ( present) Social characteristics Marital status (married) Number of households (mean ± SD, range) Education (>9 year) Job Employed Unemployed Housewife Confidants ( present) Satisfaction with confidantsa (mean ± SD, range) Experience of cancer death of relatives
16 31 63
(14.5) (28.2) (57.3)
55 52 3
(50.0) (47.3) (2.7)
100 4 6 17 85.7 ± 9.8 48 44 10
(90.1) (3.6) (5.5) (15.5) (60–100) (43.6) (40.0) (9.1)
87 2.9 ± 1.4 99
(79.1) (1–10) (90.0)
59 32 19 104 5.8 ± 1.0 49
(53.6) (29.1) (17.3) (94.5) (3–7) (44.5)
SD, standard deviation; PTCD, percutaneous transhepatic cholangiodrainage; KPS, Karnofsky performance status. a Coded as 1 (very dissatisfied), 2 (fairly dissatisfied), 3 (slightly dissatisfied), 4 (neither), 5 (somewhat satisfied), 6 (fairly satisfied) and 7 (very satisfied).
(resectable, locally advanced, metastatic) (20), tumor location (pancreatic head, body to tail or diffuse), histology, percutaneous transhepatic cholangiodrainage (present or absent) and Karnofsky Performance Status (KPS) (21). We used clinical radiographic staging because TMN staging does not directly correlate with treatment prognosis, and lymph node status cannot be determined without surgical treatment (20). Histology was confirmed by needle biopsy of tumors or surgical operation samples. The following psychosocial factors were determined based on structured interviews: alcohol drinking habits, smoking habits, education, job status, marital status, number in household, prior experience with death of a family member due to cancer, past history of major depression and whether or not the patient had a confidant and their satisfaction with him/her. Factors related to confidants were assessed by the structured interview as an indicator of social support (22). Physical symptoms were assessed using the Japanese version of the M.D. Anderson Symptom Inventory (MDASI) (23). The MDASI is a self-rated questionnaire consisting of six functional interference items and the following 13-symptom severity scale items: pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, difficulty remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting and numbness or tingling. Each item was rated on a numeric scale from
We estimated that the prevalence of depression and anxiety in Japanese patients with pancreatic cancer was ∼20% (25,26). To achieve a 10% margin of error at 99% confidence level, it needed 107 participants. In consideration of incomplete assessment, we concluded that 130 participants would be the adequate sample size.
Statistical analysis We performed descriptive analyses and compared the characteristics of patients who agreed to participate with those who did not, using the independent t-test and the χ 2 test. We identified the prevalence of depression and anxiety and calculated the appropriate confidence intervals (CI). Thus, we compared the onset of depression and anxiety with that of the first physical symptom of pancreatic cancer. To identify baseline predictive factors for depression and anxiety at follow-up, subjects who had no psychiatric diagnosis and completed follow-up assessment were divided into two groups based on the presence of newly diagnosed depression and anxiety at the follow-up, and then we conducted preliminary bivariate analysis and logistic regression analysis (backward elimination method). We entered the onset of depression and anxiety at the follow-up as objective variable, and demographic and biomedical factors, psychosocial factors and physical symptoms (MDASI) as explanatory variables. Items with P < 0.25 in bivariate analysis were used in the logistic regression analysis. A P value of 9 years) Marital status (married) Having children Job (Employed) Confidant ( present) Past history of major depression Exp. of cancer death of relatives MDASI (≤5) Pain Fatigue Nausea Disturbed sleep Distress Shortness of breath Remembering things Lack of appetite Drowsy Dry mouth Sad Vomiting Numbness or tingling
SD
Mean
SD
58.6 79.1 3.4 4.2
10.6 11.4 1.1 1.5
61.2 87.9 2.6 5.6
10.6 8.7 1.2 4.7
0.44
