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183 Suicidality in Terminally Ill Japanese Patients with Cancer Prevalence, Patient Perceptions, Contributing Factors, and Longitudinal Changes Tatsuo Akechi, M.D., Ph.D.1,2 Toru Okuyama, M.D., Ph.D.1 Yuriko Sugawara, M.D.1 Tomohito Nakano, M.D.3 Yasuo Shima, M.D.4 Yosuke Uchitomi, M.D., Ph.D.1,2 1 Division of Psycho-Oncology, National Cancer Center Research Institute East, Kashiwa, Japan. 2 Division of Psychiatry, National Cancer Center Hospital East, Kashiwa, Japan. 3 Division of Psychiatry, National Cancer Center Hospital, Tokyo, Japan. 4 Palliative Care Unit, National Cancer Center Hospital East, Kashiwa, Japan. Supported in part by a Grant-in-Aid for Cancer Research (11-2) from the Japanese Ministry of Labor, Health and Welfare and by a Grant-in-Aid for Young Scientists (B) from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The Authors thank the patients involved in the current study, who gave their time so willingly. They also thank Dr. Tatsuya Morita of the Seirei Mikatabara Hospital (Hamamatsu, Japan) for his helpful comments and Yurie Sugihara and Ryoko Katayama for their research assistance. Address for reprints: Yosuke Uchitomi, M.D., Ph.D., Division of Psycho-Oncology, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan; Fax: (011) 81 471 34 7026; E-mail: [email protected] Received June 9, 2003; revision received September 4, 2003; accepted September 15, 2003. © 2003 American Cancer Society DOI 10.1002/cncr.11890 BACKGROUND. The risk of suicide is higher in patients with cancer than in the general population, making end-of-life care of suicidal terminal patients with cancer critical. To identify factors and longitudinal changes associated with suicidality among terminally ill Japanese patients with cancer, a prospective cohort study was performed. METHODS. Consecutive outpatients with cancer who registered with a palliative care unit participated. Structured interviews (e.g., Structured Clinical Interview for DSM-III-R [SCID]) were conducted to assess patient suicidal ideation (Ideation) and interest in requesting euthanasia (Interest) as main outcome measures of suicidality. Possible correlated factors also were investigated. The authors analyzed the data from 140 terminally ill patients with cancer at initial study participation (baseline) whose subsequent survival time was ⬍ 6 months. Of these 140 patients, 57 (40.7%) completed the follow-up assessment after admission to the unit. RESULTS. At baseline, 8.6% of the patients had Ideation and 5.0% had Interest. Self-reported anxiety and depression was significantly associated with Ideation (P⫽ 0.003). Changes in Ideation and Interest occurred in 38.6% and 15.8% of the patients, respectively. Ideation was more likely to change than Interest (P ⫽ 0.006). The current study did not identify factors that predict changes and occurrences of suicidal ideation and interest in requesting euthanasia. CONCLUSIONS. Suicidality can change even in terminally ill patients. End-of-life care that focuses on the psychologic distress of dying individuals may be a way of preventing suicide. Cancer 2004;100:183–91. © 2003 American Cancer Society. KEYWORDS: suicide, terminally ill, terminal care, suffering, culture. P revious epidemiologic studies indicated that the risk of suicide is higher among patients with cancer than in the general population and that one of the important risk factors is advanced disease.1 In addition, a previous study conducted in the United Kingdom found that in a 5-year period, patient suicide and suicide attempts occurred in greater than one-third and two-thirds of hospices, respectively.2 Furthermore, many people, including health professionals, consider suicide a rational and justifiable choice in the face of the severe physical and emotional pain that can afflict patients with cancer. This opinion is reinforced by the general perception of cancer as a disease characterized by severe suffering, whose inevitable outcome is death, not cure.3 In contrast, only two psychologic autopsy studies have actually investigated suicide victims among patients with cancer.4,5 These studies suggested that several physical, psychologic, and existential distress factors (e.g., pain, impairment of physical functioning, depression, loss of independence, and loss of autonomy) are associ- 184 CANCER January 1, 2004 / Volume 100 / Number 1 ated with suicide in patients with cancer. It recently was reported that ⬎ 30,000 people in Japan commit suicide annually, one of the highest suicide rates in the world. Health problems were cited as the most common risk factor.6 Although suicidality in terminally ill patients with cancer is critically important in clinical oncology practice, very few studies have addressed these issues. It is not rare for physicians in clinical practice in Western countries and in Japan to receive requests for early death from patients.7,8 However, these requests confront the medical staff with a dilemma. Several recent studies have demonstrated that the prevalence of the “desire for death” in terminally ill patients with cancer is not particularly low (range, 8.5–22.2%).9 –14 These studies demonstrated that pain, weakness, concerns with physical symptoms, especially pain, loss of control, psychologic distress, such as depression, hopelessness, demoralization, and perception of being a burden to others, and social support factors are significantly associated with the desire for death. Cognitive dysfunction and delirium also have been suggested as factors that may increase the likelihood of suicide.15,16 In regard to cultural differences in attitudes to euthanasia/physician-assisted suicide (PAS), Western surveys have indicated that ⬎ 50% of the general population support legalization of euthanasia or PAS for incurable patients with cancer,15 whereas a Japanese survey found that only 13% of the general population endorse euthanasia.17 In Japan, 2.0 –5.0% of oncologists and/or palliative care physicians have reported actual experience with euthanasia for terminally ill patients with cancer despite the illegality of such medical intervention.8,18 Although adequate care for suicidal terminal patients with cancer is critical, very few studies have addressed the form that the care should take. Identification of patients at increased risk of suicide and recognition of the underlying factors in patients with cancer with suicidality are important steps in suicide prevention and allow appropriate intervention for suicidal patients with cancer. However, to our knowledge, no study has addressed longitudinal changes in, or predictors of, suicidality, such as suicidal ideation and interest in requesting euthanasia, in terminally ill patients with cancer. The goals of the current study were to replicate previous findings obtained in Western studies9 –12,14 and to answer the following six questions concerning suicidality among terminally ill Japanese patients with cancer with the aim of establishing a useful strategy for suicide prevention: 1) How prevalent are suicidal ideation and interest in requesting euthanasia? 2) What are patient perceptions regarding the reasons for suicidal ideations? 3) What factors are associated with suicidal ideation? 4) What factors contribute to interest in requesting euthanasia among patients with suicidal ideation? 5) Are there longitudinal changes in suicidal ideation and interest in requesting euthanasia and do any factors predict these changes? 6) What factors predict occurrences of suicidal ideation and interest in requesting euthanasia? MATERIALS AND METHODS Patients Consecutive patients who registered with the Palliative Care Unit (PCU), National Cancer Center Hospital East (Kashiwa, Japan) between October 1997 and November 1999 and met the inclusion criteria were recruited (Table 1). The PCU has an outpatient service and a 25-bed inpatient service. In principle, patients register with the outpatient service and are admitted to the inpatient service mainly for symptom management, terminal care, and respite care for the family. The most common reasons for patient registration and admission are physical symptoms. Eligibility criteria for enrollment in the current study included the following: age ⱖ 18 years, new registration with the PCU, no current curative cancer treatment, awareness of the cancer diagnosis, absence of illness that would prevent the patient from completing the questionnaires and participating in an interview, no apparent cognitive impairment (Mini Mental State [MMS] score ⱖ 24),19,20 and no difficulty with verbal communication. Because patients registered with the PCU have a broad range of life expectancies and because information from terminally ill patients with cancer was considered essential, we followed up all participants. However, we only analyzed the data from patients whose death was confirmed to have occurred within 6 months of participation of the initial assessment. Suicidality (Suicidal Ideation, Patient Perceptions, and Interest in Requesting Euthanasia) We assessed patients’ suicidal ideation as suicidality because it is a well-known indicator of patients’ suicidal behavior.21 We also assessed patients’ perceptions regarding their suicidal ideation to understand why they wanted to die. First, before interviewing patients regarding suicidal ideation, trained psychiatrists asked the subjects about the presence or absence of such feelings as wanting to escape from their disease and going away as a means of avoiding psychologic harm. Second, suicidal ideation was assessed at the time of the patient’s first visit to the outpatient clinic after registering with the PCU (baseline) and again at admission (follow-up) and was classified as absent, subthreshold, or present by using the suicidal Suicidality in Terminally Ill Patients/Akechi et al. TABLE 1 Patient Characteristics (n ⴝ 140) Characteristic Age Mean ⫾ SD Range No. of males Education ⱖ 12 yrs Marital status Married Never married Divorced Separated Widowed Unknown Household size Living alone Cancer site Lung Colon Pancreas Stomach Head and neck Other Time since cancer diagnosis Mean ⫾ SD Median Range Past cancer treatment Surgery Chemotherapy Radiotherapy Current medication Opioids Antidepressants Anxiolytics Religion Buddhist Catholic/Protestant Other None Survivala Median Mean ⫾ SD Range No. of patients (%) 61 ⫾ 10 yrs 38–89 yrs 92 (66) 92 (66) 121 (86) 5 (4) 3 (2) 1 (1) 9 (6) 1 (1) 7 (5) 57 (41) 17 (12) 13 (9) 11 (8) 11 (8) 31 (22) 22 ⫾ 38 mos 13 mos 0–282 mos 61 (44) 81 (58) 51 (36) 62 (44) 4 (3) 19 (14) 3 (2) 2 (1) 8 (6) 127 (91) 61 days 70 ⫾ 43 days 2–176 days SD: standard deviation. a Survival (days) since the date of the initial assessment. ideation item (recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide) of the major depressive episode module of the Structured Clinical Interview for DSM-III-R (SCID).22 If suicidal ideation was judged to be present at baseline, the patient was asked an open-style question, such as, “May I ask you why you think you have such thoughts?” The patient’s responses were recorded in a descriptive manner. 185 As another indicator of suicidality, patients were asked at baseline and at follow-up about their interest in requesting euthanasia (“Would you ask a member of the medical staff to end your life now if the physician agreed with such a procedure?”). Their replies were scored as 1 (no), 2 (maybe), 3 (probably), or 4 (yes). The wording of this question was based on our clinical experience. The patients also were asked about actually requesting euthanasia. Biomedical and Psychosocial Factors Sociodemographic, biomedical, and psychosocial factors were investigated at baseline to explore factors associated with and predicting suicidal ideation, as well as factors contributing to and predicting interest in requesting euthanasia. A structured interview was conducted to identify demographic factors, Karnofsky performance status, and three common and distressing physical symptoms (pain, dyspnea, and fatigue on a scale of 1 [none] to 5 [severe]). Current and past major depression was evaluated on the basis of the SCID.22 However, because suicidal ideation is one of the diagnostic criteria, we adopted a modified method in which we diagnosed current major depression when patients fulfilled more than five of the eight original DSM-III-R criteria, excluding the suicidal ideation item.22 The Hospital Anxiety and Depression Scale (HADS) was used to evaluate psychologic distress.23,24 We asked about several different types of concerns, including financial burden, future health status, pain, dependence on others, being a burden on others, and loss of dignity (scored from 1 [not at all] to 5 [very much]).25 Patients’ use of confidants (presence and satisfaction) was assessed by a structured interview as an indicator of social support26 and their score on the MMS was used as a measure of cognitive function. Consent and Study Procedures The study was approved by the institutional review board and the ethics committee of the National Cancer Center of Japan. Written consent was obtained after each patient had been fully informed of the purpose and the approved protocol of the study. Patients who registered with the PCU were invited to participate in the study. After obtaining patients’ consent, trained psychiatrists administered the MMS, and eligible patients participated in the interview and completed the questionnaires in the outpatient clinic (baseline). The baseline investigation was conducted on the first visit after PCU registration. Of the patients admitted to the PCU, those whom investigators, physicians, and nurses considered capable of participating in the follow-up study were again administered the 186 CANCER January 1, 2004 / Volume 100 / Number 1 TABLE 2 Factors Associated with Suicidal Ideation in Terminally III Patients with Cancer: Univariate Analysis Suicidal ideation Characteristic Age (yrs) HADSc Education (yrs) Performance statusd Paine Dyspneae Fatiguee MMSf Concernse Financial Pain Future physical condition Dependence on others Burden on others Loss of dignity Satisfaction with confidantsg Male gender Marital status (married) Living alone Major depression History of major depression Absence of confidants Absence of religious belief Present (n ⴝ 12) Mean (SD)/No. (%)a Analysis Absent (n ⴝ 128) Mean (SD)/No. (%)a Test statisticb df P 54 (12) 19.6 (5.2) 13 (3) 62 (12) 2.4 (1.1) 2.1 (0.9) 2.9 (0.9) 27.9 (2.1) 61 (10) 11.8 (6.4) 12 (3) 70 (14) 1.9 (0.9) 2.1 (1.0) 2.2 (1.1) 27.3 (1.9) 2.26 ⫺3.95 ⫺0.53 0.93 ⫺1.68 ⫺0.27 ⫺2.29 ⫺1.01 138 137 — — — — — — 0.03 0.0001 0.60 0.05 0.09 0.79 0.02 0.29 3.2 (1.5) 3.8 (1.4) 3.8 (1.4) 2.7 (1.6) 3.4 (1.4) 2.1 (1.6) 4.9 (1.5) 6 (50) 11 (92) 0 (0) 4 (33) 1 (9) 0 (0) 11 (92) 2.0 (1.2) 2.7 (1.4) 3.5 (1.2) 2.0 (1.2) 2.1 (1.2) 1.4 (0.9) 5.5 (1.3) 86 (73) 110 (86) 7 (6) 5 (4) 18 (14) 19 (15) 116 (91) ⫺2.81 ⫺2.33 ⫺0.94 ⫺1.64 ⫺3.15 ⫺1.49 ⫺1.45 1.44 — — — — — — — — — — — — — 1 — — — — — — 0.005 0.02 0.35 0.10 0.002 0.14 0.15 0.23 1.00 1.00 0.003 1.00 0.37 1.00 SD: standard deviation; HADS: Hospital Anxiety and Depression Scale; MMS: Mini-Mental State examination. a Mean (SD) for all rows above Male gender. No. (%) for all other rows, including Male gender. b Test statistic is t for Age and HADS; z for Education, Performance status, Pain, Dyspnea, Fatigue, MMS, Concerns, and Satisfaction with confidants; and 2 for Male gender, Marital status (married), Living alone, Major depression, History of major depression, Absence of confidants, and Absence of religious belief. c Total score on the Hospital Anxiety and Depression Scale. d Defined by Karnofsky criteria. e Coded as 1: absent; 2: mild; 3: somewhat; 4: considerable; 5: severe. f Total score on the Mini-Mental State Examination. g Coded as 1: very dissatisfied; 2: fairly dissatisfied; 3: slightly dissatisfied; 4: neither satisfied nor dissatisfied; 5: somewhat satisfied; 6: fairly satisfied; 7: very satisfied. MMS by a trained psychiatrist. Patients who received an MMS score ⱖ 24 participated in the follow-up investigation (follow-up). Statistical Analysis Suicidal ideation was dichotomized by the interview ratings (absent/subthreshold vs. present). To explore factors associated with suicidal ideation, the variables investigated were included in a preliminary univariate analysis. To control type I error rates, the level of significance was determined by dividing the significance level (0.05) by the number of tests performed (Bonferonni correction). As a result, the significance level was set as 0.0023, because 22 tests were conducted (Table 2). Final associated factors were decided upon by entering vari- ables with significant P values into a logistic regression model. Interest in requesting euthanasia was dichotomized by the interview ratings into strong interest (yes) versus others and an appropriate univariate analysis was conducted to explore contributing factors among patients with suicidal ideation. To investigate baseline predicting factors of changes of suicidal ideation and interest in requesting euthanasia between baseline and followup, each change was classified into three groups (increase, no change, and decrease) and an appropriate analysis (e.g., analysis of variance) was conducted with a Bonferroni correction. To explore factors predicting occurrences of suicidal ideation and interest in requesting euthanasia, a univariate analysis was conducted with a Bonferroni correction at Suicidality in Terminally Ill Patients/Akechi et al. baseline among patients with no suicidal ideation and no interest in requesting euthanasia, respectively. All P values reported are two tailed. All statistical procedures were conducted with SPSS Version 10.0J software (SPSS, San Diego, CA). Descriptive data expressed by patients regarding their reasons for suicidal ideation were analyzed by content analysis.27 First, two investigators (T.A., Y. Su.) independently categorized the statements with regard to the similarities and differences between their reasons in the context. Discordances were resolved through discussions. The validity of the categorization was confirmed by the consensus of the authors. The reliability coefficients of the interviews by 2 independent trained psychiatrists were 0.80 for suicidal ideation, 0.91 for interest in requesting euthanasia, and 1.00 for major depression. RESULTS In the current study, 764 terminally ill patients with cancer were registered with the PCU during the study entry period. Of these, 507 patients were ineligible for study entry (too ill, n ⫽ 443; cognitive impairment, n ⫽ 50; age ⬍ 18, n ⫽ 1; not informed of the cancer diagnosis, n ⫽ 3; difficulty with verbal communication, n ⫽ 10). Of the remaining 257 eligible patients, 28 refused to participate and 20 could not be contacted (e.g., because of emergency admission to another hospital). Therefore, 209 patients participated in the baseline assessment. Of these, 69 patients were excluded (survived ⬎ 6 months, n ⫽ 56; unknown survival, n ⫽ 13). Ultimately, the data for the remaining 140 patients whose survival time was confirmed to have been ⬍ 6 months were analyzed (Table 1). The median survival time after participation in the initial assessment was approximately 2 months. Demographic data, such as age, gender, and disease site, were similar to the corresponding data for patients receiving palliative care in Japan.28 The social status (based on education, marital status, and household size) of patients in the current study also was similar to that of most Japanese patients with cancer.26 After the baseline investigation, 25 patients were never admitted to the PCU (e.g., because of emergency admission to another hospital), whereas the other 115 were admitted. However, 3 refused to cooperate further and 55 were judged to be ineligible (too ill, n ⫽ 39; cognitive impairment, n ⫽ 16). Therefore, 57 of the subjects completed the follow-up assessment. The mean interval between the baseline and follow-up investigations was 45 ⫾ 36 days (median, 35 days), and the mean ⫾ standard deviation and median survival times between the follow-up investigation and death were 39 ⫾ 26 and 37 days, respectively. 187 TABLE 3 Factors Associated with Suicidal Ideation in Terminally Ill Patients with cancer: Multivariate Logistic Regression Analysis (n ⴝ 140) Characteristic Beta SE Odds ratio 95% CI P HADSa Concern about being a burden on othersb 0.17 0.06 1.19 1.06–1.34 0.003 0.49 0.27 1.64 0.97–2.75 0.06 SE: standard error; CI: confidence interval; HADS: Hospital Anxiety and Depression Scale. a Total score on the Hospital Anxiety and Depression Scale. b Coded as 1: absent; 2: mild; 3: somewhat; 4: considerable; 5: severe. At the baseline assessment, suicidal ideation was subthreshold in 37 patients (26.4%) and present in 12 (8.6%). No patients reported an actual suicidal attempt. Interest in requesting euthanasia was strong (‘yes’) for 7 patients (5.0%), moderate (‘probably’) for 4 patients (2.9%), and weak (‘maybe’) for 7 patients (5.0%). One patient (0.7%) gave no answer. No patients reported actually requesting euthanasia. Four major reasons for suicidal ideation were elicited (multiple answers): physical distress (n ⫽ 3), anxiety/fear regarding the future course of the illness (n ⫽ 2), hopelessness (n ⫽ 4), and burden on family (n ⫽ 3). The causes of the physical distress were pain (n ⫽ 3) and dyspnea (n ⫽ 1). Anxiety/fear regarding the future course of the illness consisted of the fear of future pain (n ⫽ 1) and uncertainty of the future (n ⫽ 1). The HADS total score and concerns about being a burden on others were significant factors associated with suicidal ideation (Table 2). The logistic regression model identified only HADS as a final significant factor (Table 3). As a result of this finding, we investigated whether there was an interaction effect between HADS and religious belief in regard to suicidal ideation because a previous study had found that spirituality and faith might buffer the effect of depression on desire for hastened death.29 However, there was no significant interaction (beta ⫽ 0.014, P ⫽ 0.85). Among the 12 patients with present suicidal ideation, 6 (50.0%) expressed strong interest (‘yes’) in requesting euthanasia, 1 (8.3%) moderate interest (‘probably’), and 2 (16.7%) weak interest (‘maybe’). One patient (8.3%) gave no answer, and 2 patients (16.7%) expressed no interest. Among the variables investigated, none were significant factors contributing to interest in requesting euthanasia (data not shown). A change in suicidal ideation between PCU registration (baseline) and admission (follow-up) was documented in 22 (38.6%) of the 57 patients who were 188 CANCER January 1, 2004 / Volume 100 / Number 1 followed up. Eleven patients each experienced an increase and decrease in suicidal ideation (19.3% and 19.3%, respectively). Nine patients (15.8%) had a change in interest in requesting euthanasia. Four patients (7.0%) had increased interest, and 5 (8.8%) had decreased interest. The proportion of patients with observed longitudinal change was significantly higher for suicidal ideation (38.6%) than for interest in requesting euthanasia (15.8%; chi-square, 7.49, df ⫽ 1, P ⫽ 0.006). Among the variables investigated, none were significant factors for predicting changes in suicidal ideation and interest in requesting euthanasia (data not shown). Suicidal ideation occurred in 10 of the 40 patients without suicidal ideation at baseline. None of the baseline variables investigated significantly predicted its occurrence (data not shown). Among the 51 patients with no interest in requesting euthanasia at baseline, interest developed in 4 patients. None of the baseline factors significantly predicted its occurrence (data not shown). DISCUSSION The prevalences of suicidal ideation and interest in requesting euthanasia in the current study were essentially consistent with those reported in previous studies,9 –14 suggesting that neither is uncommon among terminal patients with cancer. These findings suggest that the proportion of terminally ill patients with cancer who are suicidal is similar, irrespective of cultural and social differences, and that the issues should be addressed even in routine care. Our findings regarding perceptions of the reasons for suicidal ideation suggest that individual patients perceive different factors, including physical, psychologic, and existential distress, as the causes of their suffering. It is noteworthy that these findings are almost the same as the results of an Italian psychologic autopsy study that investigated the characteristics of terminally ill patients with cancer who committed suicide5 and a qualitative Australian study that investigated factors associated with the wish to hasten death in terminally ill patients with cancer.14 These issues should be addressed in patients with suicidal ideation. The findings also suggest that comprehensive palliative care may be the best means of preventing suicide among terminally ill patients with cancer. Another Italian study suggested that continuous care provided by a palliative care team may be able to reduce suicide even among terminally ill patients with cancer.30 Because previous studies investigating the associations between the desire for death and major depression have consistently indicated the existence of an association,9,11,12 one noteworthy finding in the current study may be that major depression is not independently associated with suicidal ideation. Because self-reported anxiety and depression were significant factors associated with suicidal ideation in the current study, psychologic distress, rather than a clinical diagnosis of major depression, is a more important indicator of suicidal ideation in terminally ill Japanese patients with cancer than in their non-Japanese counterparts. From this standpoint, the demoralization syndrome proposed by Kissane et al.31 as a new psychiatric diagnosis for palliative care may be worth investigating in future studies because it has been suggested to be associated with desire to die or with committing suicide. For example, it is characterized by helplessness, loss of meaning, and existential distress. There may be other explanations for the finding that major depression is not independently associated with suicidal ideation. For example, several differences between the current and previous studies9,11,12 might have given rise to such different results, such as outcome measures (suicidal ideation vs. desire for death), study setting (PCU registration vs. admission), diagnosis of major depression (modified vs. standard criteria), and the statistical significance level finally adopted (conservative vs. standard). Furthermore, there is a generally lower prevalence rate of major depression in Asian countries, both among patients with cancer and among the general population, compared with Western countries, possibly because of crosscultural differences (e.g., social stigma, cultural reluctance to acknowledge mental symptoms, and low divorce rate). This epidemiologic difference may be responsible for the inconsistent findings.32 Nonetheless, our results confirm that psychologic burden is an important factor in understanding suicidality among terminally ill patients with cancer. To enable patients to deal with psychologic distress, education and training of physicians engaged in end-of-life care are critical. Physical distress, especially pain, which the general public and patients with cancer often give as a reason for supporting legalization of euthanasia/ PAS,15 was not associated with suicidal ideation. Our findings support the study by Emanuel,33 who reported that although pain may be regarded as the major reason for supporting euthanasia/PAS, psychologic distress actually is more likely than pain to increase patient suicidality. In any event, because individuals with psychologic distress are more likely to have suicidal ideation, psychologic care focused on terminally ill patients is essential for reducing patient suicidality. A previous study suggested a discrepancy between Suicidality in Terminally Ill Patients/Akechi et al. suicidality and interest in euthanasia/PAS. Ganzini et al.34 demonstrated that only 14% of patients with amyotrophic lateral sclerosis who were willing to consider PAS had thought about committing suicide in the previous 2 weeks. The results of the current study did not identify factors that contribute to interest in requesting euthanasia by patients with suicidal ideation, possibly because of the small sample size. Large studies are needed to clarify such factors. Our findings showed changes in suicidal ideation and interest in requesting euthanasia to be highly variable. Emanuel et al.35 reported that onehalf of terminally ill patients (52% of the subjects had cancer) who had considered euthanasia or PAS changed their minds, whereas an almost equal number had begun to consider them. Although there are several differences between that study and the current one (e.g., subjects, setting, outcome measures, mean follow-up time), similar results were obtained. Our findings corroborate the instability of suicidality in terminally ill patients. Another noteworthy finding is the difference in stability in regard to suicidal ideation and interest in requesting euthanasia. The results of the current study demonstrate that suicidal ideation is more changeable than interest in requesting euthanasia. This finding may reflect the different natures of suicidal ideation and interest in requesting euthanasia. The current study did not identify factors that predict changes and occurrences of suicidal ideation and interest in requesting euthanasia. This may be because of the relatively small sample size or lack of several potentially important factors. Several recent studies have demonstrated the importance of spiritual and/or existential factors (e.g., demoralization, hopelessness, dignity, and spiritual well-being) and family function as associated with suicidality in terminally ill patients with cancer.14,29,36,37 These may be promising factors to investigate. Further investigation is needed to clarify predictive factors for suicidality to prevent suicide and suffering among terminally ill patients with cancer. The current study yielded several findings regarding cross-cultural aspects of suicidality and attitudes toward euthanasia that differ between Western and Japanese terminally ill patients with cancer. Western individuals generally are more likely to support euthanasia among terminally ill patients and more reluctant to accept suicide than Japanese individuals.15,17,38,39 Japanese public awareness, legal status, and the social movement for euthanasia/ PAS are quite different from those in Western countries.40 For example, Japan is more conservative in its view of the individual’s right to die and no leg- 189 islation has addressed the question of euthanasia and/or PAS in Japan.41 Religious differences also should be considered. There is modest empiric evidence that religion protects against suicide in the general population in Western countries. However, in Japanese society, where the Buddhist influence prevails, suicide is not considered to be sinful, in contrast to Christianity.41,42 A recent American study demonstrated that spirituality and faith may buffer the effect of depression on desire for hastened death.29 Our findings suggest that active religious practice is variable as well as infrequent in Japanese terminally ill patients with cancer and that the role and influence of religion on suicidality in these patients may be different from its role and influence in Western countries. However, because the religion of the patients was heterogenous and the number of the patients was small in the current study, we could not confirm the role and influence of religion on Japanese patients with cancer. Additional studies are needed to clarify this issue in Japan. In contrast, the prevalences of suicidal ideation and interest in euthanasia are similar, as is the importance of psychologic burden rather than physical symptoms as a factor associated with patient suicidality, and the stability of suicidality also is similar. Therefore, there appear to be many similarities in suicidality between terminally ill patients with cancer in Western countries and Japan, despite the many cultural differences. These comparative findings suggest that the suffering experienced by terminally ill patients with cancer may be universal, irrespective of individual culture. The current study has several limitations. First, our sample size was not very large and the sample size in the qualitative study was especially small. Because only 18.3% (140 of 764) and 7.5% (57 of 764) of patients at baseline and follow-up, respectively, were included in the analysis, generalization of the findings obtained may be problematic. Second, institutional bias may have occurred. For example, the study was conducted in one institution, and the background of the subjects was somewhat different from that of individuals in the general population in Japan who die of cancer. For example, the age of the participants in the study was younger, and the proportion of patients with stomach malignancies was lower. Third, potentially important factors, especially validated measurements of hopelessness, personality, and existential distress, were lacking and may have distorted the results. Fourth, the timing of the follow-up assessment (admission) may also have produced distortions because the reasons for admission may have differed. Fifth, because the sui- 190 CANCER January 1, 2004 / Volume 100 / Number 1 cidal ideation and interest in requesting euthanasia are not the same as completed suicide, the findings obtained may not be directly applicable to the establishment of a suicide prevention strategy. 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