Psychosomatics 2015:56:190–195
& 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Original Research Reports Suicide Attempts in Patients With Systemic Lupus Erythematosus: A Single-Center Experience and Literature Review Kuo-Tung Tang, M.D., Chia-Wei Hsieh, M.D., Tsu-Yi Hsieh, M.D., Joung-Liang Lan, Ph.D., Yi-Hsing Chen, Ph.D., Der-Yuan Chen, Ph.D.
Background: Suicide is a global health issue, and an increase in suicide risk has been found in patients with systemic lupus erythematosus (SLE) when compared with the general population. However, only a few studies have described suicide attempts in patients with SLE in detail. Objective: The aim of this study is to describe the suicide attempts in patients with SLE in a tertiary hospital in Taiwan. Methods: A total of 8 patients with SLE, 7 women and 1 man, with 12 suicide attempts among them were identified among 2469 patients visiting a tertiary medical center in Taiwan, from March 1, 2003 to November 30, 2013. Their demographic data, lupus manifestations throughout their disease course, laboratory data, and details of their suicide attempts were retrospectively documented. We also searched the MEDLINE database and found 4 articles in English
describing suicide attempts in 14 patients with SLE. Results: The median age of the 8 patients with SLE in our hospital who attempted suicide was 33 years (range: 19– 77 years). Neuropsychiatric SLE developed in 5 (63%) of these patients before the attempts, and psychiatric disorders were diagnosed in 5 (63%) of them. We also observed a high prevalence of neuropsychiatric SLE (71%) and psychiatric disorders (86%) in patients with SLE in the literature who had attempted suicide. Conclusion: We demonstrated that previous neuropsychiatric SLE and comorbid psychiatric disorders are prevalent in patients with SLE who attempt suicide. If a rheumatologist suspects that a patient with SLE has a psychiatric disorder, he or she should refer the patient to a psychiatrist. (Psychosomatics 2015; 56:190–195)
INTRODUCTION Suicide is a global health issue, with an estimated burden of 1 million deaths by suicide every year.1 It is well established that mental and physical illnesses are associated with an increased suicide risk.2 Tang and Crane indicated that patients with chronic pain had at least a 2-fold risk of death by suicide.3 Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and its manifestations, such as arthritis, are associated with long-lasting pain.4,5 In addition, many studies have demonstrated an increased prevalence of mental disorders, such as depression and psychosis, in patients with SLE.6,7 These patients are therefore at a risk for suicidal behavior. In a review conducted by Harris and Barraclough, a 4-fold increase in suicide risk was found 190
www.psychosomaticsjournal.org
Received April 13, 2014; revised May 19, 2014; accepted May 19, 2014. From Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC (K-TT, C-WH, T-YH, J-LL, Y-HC, D-YC); School of Medicine, National YangMing University, Taipei, Taiwan, ROC (C-WH, J-LL, Y-HC, D-YC); Division of Immunology and Rheumatology, China Medical University Hospital, Taichung, Taiwan, ROC (J-LL); College of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC (J-LL); Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, ROC (D-YC); Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan, ROC (D-YC). Send correspondence and reprint requests to Der-Yuan Chen, Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Blvd., Taichung 40705, Taiwan, ROC. e-mail: [email protected] & 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Psychosomatics 56:2, March/April 2015
Tang et al. in patients with SLE when compared with the general population.8 However, only a few studies have described suicide attempts in patients with SLE in detail.9,10 The aim of this study is to describe the suicide attempts in patients with SLE in a tertiary hospital in Taiwan. MATERIALS AND METHODS Patients A total of 8 patients with SLE, 7 women and 1 man, with 12 suicide attempts among them were identified among 2469 patients with SLE on regular follow-up at Taichung Veterans General Hospital, a tertiary medical center in Taiwan, from March 1, 2003 to November 30, 2013. A suicide attempt was defined as an act of selfharm with suicidal intent, despite the outcome.11 All the identified patients fulfilled the 1997-revised American College of Rheumatology criteria for SLE.12 Their demographic data, lupus manifestations throughout their disease course, laboratory data, and details of their suicide attempts were retrospectively documented, using a standard data extraction form. This study was performed in compliance with the Declaration of Helsinki, and the Institutional Review Board of Taichung Veterans General Hospital approved the study protocol. Clinical Manifestations of SLE The diagnosis of neuropsychiatric SLE (NPSLE) was based on the clinical judgment of the attending physician and classified according to the 1999 American College of Rheumatology case definitions.13 The presence of antiphospholipid antibodies and antiphospholipid antibody syndrome was defined as in the revised Sapporo classification criteria.14 Disease activity of SLE was assessed by the change in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score.15 However, serologic markers of disease activity in patients with SLE, such as anti–double-stranded DNA antibodies (antidsDNA), complement 3 (C3), and complement (C4), were seldom measured at the time these patients attempted suicides. Therefore, levels of anti-dsDNA, C3, and C4, measured within a month before or after the suicide attempt, were used in SLEDAI scoring instead. A disease flare was defined as greater than a 3-point change in the SLEDAI score.16 An active serology was defined as either a decrease in the levels of C3 or C4 less than the lower limit of the normal range or an Psychosomatics 56:2, March/April 2015
increase in the levels of anti-dsDNA more than the upper limit of the normal range when compared with last test values. Damage accrual of SLE was assessed by the Systemic Lupus International Collaborating Clinics (SLICC) damage index.17 The Charlson comorbidity index (CCI), an index that assesses both the number and severity of 19 comorbid conditions,18 was calculated for each enrolled patient with lupus. All comorbidities included in the CCI were physical disorders except dementia. SLE, as a connective tissue disease, was scored 1 in the CCI, and therefore, the lowest possible score was 1 for all the enrolled patients with SLE. Literature Review We searched the MEDLINE database (National Library of Medicine, Bethesda, MD). Only articles in English that were published before September 2013 were reviewed, and pediatric cases (r16 years old) were excluded. We found 4 articles describing suicide attempts in patients with SLE in detail.9,10,19,20 Demographic data as well as lupus manifestations, laboratory data, and details of suicide attempts in these patients with SLE were extracted from the literature. Statistics Statistical analysis was performed using SPSS software version 15.0 (SPSS Inc., Chicago, IL). Descriptive statistics for the demographic data, laboratory parameters, lupus manifestations, suicide methods, management, and outcomes of the enrolled patients with SLE in our hospital and in the literature were obtained. RESULTS Demographic Data and Clinical Characteristics of Patients With SLE in Our Hospital Who Attempted Suicide In our hospital, 8 of 2469 patients with SLE (0.3%) attempted suicide in the study period. The demographic data and clinical characteristics of our patients with SLE who attempted suicide are illustrated in Table 1. The median age of the patients was 33 years (range: 19–77 years). The median duration of SLE before the suicide attempt was 6 years, and 6 patients (75%) attempted suicide within 10 years of disease onset. Notably, NPSLE developed in 5 (63%) of our patients with SLE before the suicide attempt (acute confusion in patient 1, www.psychosomaticsjournal.org
191
Suicide Attempts in Patients With Systemic Lupus Erythematosus TABLE 1.
Clinical Characteristics of the 12 Suicide Attempts in 8 Patients With SLE in Our Hospital
Patient Age Psychiatric (y)/sex disorders 1 2 3
33/F 77/M 49/F
4
25/F
– – Reactive depression Mental retardation
SLICC CCI Duration from the onset of SLE (y)
25/F
6 7
19/F 32/F
7 7 7 8
39/F
1 4 1
11 3 11
2 2 4
þ þ þ
Insecticide poisoning Overdose of clonazepam Overdose of hypnotics
3
3
7
2
N.A.
Overdose of sulpiride
8
0
þ
1
5
2
þ
Overdose of meloxicam, liquid brown mixture, antiepileptics, and sulpiride Overdose of sertraline and Lexotan
1 1
5 4
0 0
Insecticide poisoning Detergent poisoning
1
4 4 4 7
2 2 0 10
þ þ þ þ
Self-removal of tracheostomy tube Self-removal of tracheostomy tube Jumping from the second floor Jumping from the 12th floor
Reactive 0 depression – 0 Reactive 1 depression
Psychosis
Suicide method Active serology*
0 0 0
4 5
Change in SLEDAI
1
CCI ¼ Charlson comorbidity index; N.A. ¼ not available; NPSLE ¼ neuropsychiatric systemic lupus erythematosus; SLE ¼ systemic lupus erythematosus; SLICC ¼ systemic lupus international collaborating clinics damage index; SLEDAI ¼ systemic lupus erythematosus disease activity index. n
An active serology was defined as, within a month before or after the suicidal attempt, either a decrease in the levels of C3 or C4 to less than the normal range or an increase in the levels of anti-dsDNA to more than the normal range when compared with last test values.
polyneuropathy in patient 2, intracerebral hemorrhage in patient 4, transient ischemic attack in patient 7, and psychosis in patient 8). Of our patients with SLE, 5 (63%) had psychiatric disorders diagnosed by a psychiatrist (depression in 3 patients, psychosis in 1 patient, and mental retardation in 1 patient), although an actual assessment by a qualified mental health professional was not performed in the other 3 patients. Interestingly, among these patients with psychiatric disorders, 4 (80%) had visited a psychiatrist on a regular basis and taken psychotropic medications before the suicide attempt. Mucocutaneous manifestations were present in 7 (88%) of our patients with SLE, but renal manifestations were present in only 2 (25%) of them. Overall, 3 (38%) patients had scores Z1 in the SLICC damage index, and all these patients had neuropsychiatric damage alone. In terms of comorbidities, only 2 patients (25%) scored Z1 in the CCI (4 for patient 2 and 3 for patient 4). Characteristics of Suicide Attempts in Patients With SLE in Our Hospital As illustrated in Table 1, most (67%) of the 12 suicide attempts involved ingestion of a drug or a
192
www.psychosomaticsjournal.org
toxin. Only 1 suicide attempt succeeded (jumping from the 12th floor) and 3 other attempts resulted in long-term sequelae, including esophageal ulcerations due to insecticide ingestion (patient 1), corrosive injury of the esophagus due to detergent ingestion (patient 7), and left calcaneal fracture and L1 spinal compression fracture due to jumping from the second floor (patient 7). A change in the SLEDAI score 4 3, indicating a lupus flare, was demonstrated in 2 (25%) patients with SLE in our hospital who attempted suicide. Serologic markers of lupus activity, examined within a month before or after the suicide attempt, were detected in 7 patients and an active serology was present in 5 (71%) of them. An argument with the family occurred before 3 suicide attempts. Previous suicidal ideation was detected in 4 attempts (33%), which were all made by patient 7. Of our patients with SLE, 2 received psychiatric interventions after the suicide attempt, but the dosage of steroids or immunosuppressants was not increased in any of them. After a median follow-up of 51 months, of 7 patients with SLE in our hospital with nonfatal suicide attempts, 2 (29%) attempted suicide again (patients 4 and 7).
Psychosomatics 56:2, March/April 2015
Tang et al.
TABLE 2. References
MacNeill et al.18 Bonfa et al.19 Matsukawa et al.8 Karrasa et al.9
Patients With SLE in the Literature Who Had Attempted Suicide Patients who had attempted suicide (n)
Number of suicide attempts
Number of Number of suicide completed attempts suicides during active SLE
1
2
1
1
1
41
N.A.
0
7
8
2
4
5
7
2
1
N.A. ¼ not available; SLE ¼ systemic lupus erythematosus.
*
Demographic Data and Clinical Characteristics of Patients With SLE in the Literature Who Had Attempted Suicide After conducting a literature review, we found 14 patients with SLE who had attempted suicide (Table 2). The median age of the patients was 32 years (range: 17–53 years). The median duration of SLE before the suicide attempt was 2.5 years in 5 patients with SLE in a study by Karrasa et al.10 For the other 9 patients with SLE in the literature who had attempted suicide, disease duration before the attempt was within 5 years for all, including 4 attempts at the onset of SLE. NPSLE developed in 10 patients with SLE (71%) who had attempted suicide, though Karrasa et al. regarded depression in all 5 enrolled patients as NPSLE instead of reactive depression.10 As for psychiatric disorders, 10 (71%) patients with SLE in the literature who had attempted suicide had depression, and 4 (29%) patients had psychosis. Disease activity of SLE was assessed in 13 patients who had attempted suicide, and a concurrent disease flare was present in 4 (31%) of them. Previous suicidal ideation was detected in 5 of 18 attempts (28%). Suicide methods were described in 17 suicide attempts. Overall, 7 (41%) attempts involved drug overdose or ingestion of a toxin and 5 attempts (29%) involved jumping from height. Excluding a patient whose outcomes of suicide attempts were not clearly described,21 6 (35%) of the remaining 17 suicide attempts resulted in fatalities. The dosage of steroids or immunosuppressive therapy was increased in 9 (75%)
Psychosomatics 56:2, March/April 2015
of 12 nonfatal suicide attempts, whereas psychotropic medications were prescribed in 6 attempts (50%). Of 11 patients with SLE with nonfatal suicide attempts, 3 (27%) attempted suicide again. DISCUSSION This study described the characteristics of patients with SLE who attempted suicide in a single center. To our best knowledge, this is the largest case series regarding suicide attempts in patients with SLE, which recruited 8 patients with SLE with 12 suicide attempts among them. The clinical data of these patients with SLE, such as the SLEDAI, SLICC, and CCI, were comprehensively collected. We have also conducted a literature review to further investigate this issue. We demonstrated that prior NPSLE and comorbid psychiatric disorders are prevalent in patients with SLE who attempt suicide. Previous psychiatric interventions might reduce lethal suicide attempts in these patients with SLE. Of the patients with SLE in our hospital, 0.3% attempted suicide in the study period, an incidence lower than that reported by Karassa et al.10 However, the study period of the latter study is twice that of ours.10 In addition, lifetime rate of suicide attempt in Taiwan has been shown to be much lower when compared with the other 7 countries in a cross-national comparison study,21 which may also explain this discrepancy. Patients with SLE usually attempted suicides within 10 years of the diagnosis, both in our patients with SLE and in such patients in the literature. Among patients with SLE in our hospital who attempted suicide, we found that 38% had damage resulting from lupus activity (scores Z1 in the SLICC damage index) within a median disease duration of 6 years, which is comparable to that in the general population with SLE, as Mok et al. demonstrated in a cohort study (38% with damage within a mean disease duration of 75 months).22 Conversely, psychiatric disorders were present in 63% of our patients with SLE who attempted suicide, a prevalence higher than that in the general population with SLE.23 The increased prevalence of psychiatric disorders (86%, data not shown), including psychosis (71%) and depression (29%), was also observed in such patients in the literature. Interestingly, NPSLE developed in 63% of patients with SLE in our hospital who attempted suicide and in 71% of such patients in the literature. Such prevalences of NPSLE were higher
www.psychosomaticsjournal.org
193
Suicide Attempts in Patients With Systemic Lupus Erythematosus than that in the general population with SLE (46% according to the revised American College of Rheumatology NPSLE criteria).24 Insomnia and tapering of steroid dose have been reported to be risk factors for suicide attempts in patients with SLE by Matsukawa et al.,9 although this was not found in patients in our hospital who attempted suicide. Most of the patients with SLE in our hospital who attempted suicide used less violent means, perhaps because of the female predominance among patients with SLE.25,26 The risk of suicide completion in patients with SLE in our hospital was 8%, which is comparable to that in the general population (attempted suicides 10 to 40 times more common than completed suicides).27 A somewhat higher risk of suicide completion (35%) in such patients in the literature was demonstrated, although a statistical significance was not achieved (p ¼ 0.187, the Fisher exact test). This discrepancy might be attributable to previous psychiatrist follow-up and psychiatric management among most of our patients with SLE (80%) who had psychiatric disorders, consistent with the finding by Parra Uribe et al. that suicide completers are less likely to have been followed up by a psychiatrist.27 Interestingly, the only 1 patient with SLE in our hospital who completed suicide was a patient with psychosis who had no previous regular psychiatrist follow-up (patient 8). However, it should be noted that patients who make more violent suicide attempts may die before they have the opportunity to be transferred to hospitals and thus may not be included in our hospital-based study. Population-based studies with a large number of patients with SLE who have attempted suicide are needed to elucidate this issue. The neurobiologic basis of suicide has long been the focus of research.28 Should a suicide attempt be regarded as a manifestation of SLE or a psychologic sequela to the physical illness? Overall, 25% of patients with SLE in our hospital who attempted suicide and 31% of such patients in the literature9,10,19,20 had a disease flare at the time of the suicide attempt. We also demonstrated an active serology in 71% of patients with SLE in our hospital who attempted suicide. For comparison, we retrospectively identified another 16 patients with SLE who have been
followed up for at least 6 years in our hospital (13 women and 3 men, median age 36 years). Of them, 7 (44%) had a disease flare and 8 (50%) had an active serology. We observed a lower prevalence of disease flares and a higher prevalence of active serology in patients with SLE who attempted suicide than in the comparison group in our hospital, although statistical significances were not achieved (p ¼ 1.000 and 0.405, the Fisher exact test). In previous studies, Matsukawa et al. found hypocomplementemia in 5 of 6 patients with SLE who had attempted suicide,9 whereas Karrasa et al. noted lymphopenia in 6 of 7 suicide attempts in patients with SLE.10 The significance of these findings remains to be answered. Our study has some limitations. Firstly, our study is hospital-based and patients with SLE who used more lethal suicide methods might not be enrolled. Therefore, the effect of suicide attempts on patients with SLE might be underestimated. However, because of female predominance among patients with SLE25 and lower suicide completion rate in women,27 it is possible that we only missed few cases. Secondly, the sample size in our study is small, making the study result less powerful. Thirdly, this study is retrospective, and as such, it is prone to biases resulting from missing data and incomplete documentation. Finally, 3 patients with SLE who were identified in our hospital have not received a formal assessment by a psychiatrist, and our results may therefore underestimate the prevalences of psychiatric disorders and suicidal ideation before the suicide attempt. In conclusion, our results showed that prior NPSLE and comorbid psychiatric disorders are prevalent in patients with SLE who attempt suicide. If a rheumatologist suspects that a patient with SLE has a psychiatric disorder, he or she should refer the patient to a psychiatrist for interventions. We sincerely thank the Clinical Informatics Research and Development Center of Taichung Veterans General Hospital for providing the clinical data of patients enrolled in the study. Disclosure: This research received grant funding from the Taichung Veterans General Hospital Research Program only. The authors declare that there is no conflict of interests.
References 1. Krug EG, Mercy JA, Dahlberg LL, Zwi AB: The world report on violence and health. Lancet 2002; 360(9339):1083–1088
194
www.psychosomaticsjournal.org
2. Hawton K, van Heeringen K: Suicide. Lancet 2009; 373 (9672):1372–1381
Psychosomatics 56:2, March/April 2015
Tang et al. 3. Tang NK, Crane C: Suicidality in chronic pain: a review of the prevalence, risk factors and psychological links. Psychol Med 2006; 36(5):575–586 4. Schmeding A, Schneider M: Fatigue, health-related quality of life and other patient-reported outcomes in systemic lupus erythematosus. Best Pract Res Clin Rheumatol 2013; 27(3):363–375 5. Waldheim E, Elkan AC, Bergman S, Frostegard J, van Vollenhoven R, Henriksson EW: Extent and characteristics of self-reported pain in patients with systemic lupus erythematosus. Lupus 2013; 22(2):136–143 6. Bachen EA, Chesney MA, Criswell LA: Prevalence of mood and anxiety disorders in women with systemic lupus erythematosus. Arthritis Rheum 2009; 61(6):822–829 7. Pego-Reigosa JM, Isenberg DA: Psychosis due to systemic lupus erythematosus: characteristics and long-term outcome of this rare manifestation of the disease. Rheumatology (Oxford) 2008; 47(10):1498–1502 8. Harris EC, Barraclough BM: Suicide as an outcome for medical disorders. Medicine (Baltimore) 1994; 73(6):281–296 9. Matsukawa Y, Sawada S, Hayama T, Usui H, Horie T: Suicide in patients with systemic lupus erythematosus: a clinical analysis of seven suicidal patients. Lupus 1994; 3(1):31–35 10. Karassa FB, Magliano M, Isenberg DA: Suicide attempts in patients with systemic lupus erythematosus. Ann Rheum Dis 2003; 62(1):58–60 11. Silverman MM, Berman AL, Sanddal ND, O’Carroll PW, Joiner TE: Rebuilding the tower of Babel: a revised nomenclature for the study of suicide and suicidal behaviors. Part 2: suicide-related ideations, communications, and behaviors. Suicide Life Threat Behav 2007; 37(3):264–277 12. Hochberg MC: Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40(9):1725 13. ACR Ad Hoc Committee On Neuropsychiatric Lupus Nomenclature: The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999; 42(4):599–608 14. Miyakis S, Lockshin MD, Atsumi T, et al: International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4(2):295–306 15. Petri M, Kim MY, Kalunian KC, et al: Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005; 353(24):2550–2558
Psychosomatics 56:2, March/April 2015
16. Buyon JP, Petri MA, Kim MY, et al: The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial. Ann Intern Med 2005; 142:953–962 17. Sutton EJ, Davidson JE, Bruce IN: The systemic lupus international collaborating clinics (SLICC) damage index: a systematic literature review. Semin Arthritis Rheum 2013; 43(3):352–361 18. Charlson ME, Pompei P, Ales KL, MacKenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40(5):373–383 19. MacNeill A, Grennan DM, Ward D, Dick WC: Psychiatric problems in systemic lupus erythematosus. Br J Psychiatry 1976; 128:442–445 20. Bonfa E, Golombek SJ, Kaufman LD, et al: Association between lupus psychosis and anti-ribosomal P protein antibodies. N Engl J Med 1987; 317(5): 265–271 21. Weissman MM, Bland RC, Canino GJ, et al: Prevalence of suicide ideation and suicide attempts in nine countries. Psychol Med 1999; 29(1):9–17 22. Mok CC, Ho CT, Wong RW, Lau CS: Damage accrual in southern Chinese patients with systemic lupus erythematosus. J Rheumatol 2003; 30(7):1513–1519 23. Jarpa E, Babul M, Calderon J, et al: Common mental disorders and psychological distress in systemic lupus erythematosus are not associated with disease activity. Lupus 2011; 20(1):58–66 24. Ainiala H, Hietaharju A, Loukkola J, et al: Validity of the new American College of Rheumatology criteria for neuropsychiatric lupus syndromes: a population-based evaluation. Arthritis Rheum 2001; 45(5):419–423 25. Whitacre CC, Reingold SC, O’Looney PA: A gender gap in autoimmunity. Science 1999; 283(5406):1277–1278 26. Denning DG, Conwell Y, King D, Cox C: Method choice, intent, and gender in completed suicide. Suicide Life Threat Behav 2000; 30(3):282–288 27. Parra Uribe I, Blasco-Fontecilla H, García-Parés G, et al: Attempted and completed suicide: not what we expected? J Affect Disord 2013; 150(3):840–846 28. Ernst C, Mechawar N, Turecki G: Suicide neurobiology. Prog Neurobiol 2009; 89(4):315–333
www.psychosomaticsjournal.org
195
& 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Original Research Reports Suicide Attempts in Patients With Systemic Lupus Erythematosus: A Single-Center Experience and Literature Review Kuo-Tung Tang, M.D., Chia-Wei Hsieh, M.D., Tsu-Yi Hsieh, M.D., Joung-Liang Lan, Ph.D., Yi-Hsing Chen, Ph.D., Der-Yuan Chen, Ph.D.
Background: Suicide is a global health issue, and an increase in suicide risk has been found in patients with systemic lupus erythematosus (SLE) when compared with the general population. However, only a few studies have described suicide attempts in patients with SLE in detail. Objective: The aim of this study is to describe the suicide attempts in patients with SLE in a tertiary hospital in Taiwan. Methods: A total of 8 patients with SLE, 7 women and 1 man, with 12 suicide attempts among them were identified among 2469 patients visiting a tertiary medical center in Taiwan, from March 1, 2003 to November 30, 2013. Their demographic data, lupus manifestations throughout their disease course, laboratory data, and details of their suicide attempts were retrospectively documented. We also searched the MEDLINE database and found 4 articles in English
describing suicide attempts in 14 patients with SLE. Results: The median age of the 8 patients with SLE in our hospital who attempted suicide was 33 years (range: 19– 77 years). Neuropsychiatric SLE developed in 5 (63%) of these patients before the attempts, and psychiatric disorders were diagnosed in 5 (63%) of them. We also observed a high prevalence of neuropsychiatric SLE (71%) and psychiatric disorders (86%) in patients with SLE in the literature who had attempted suicide. Conclusion: We demonstrated that previous neuropsychiatric SLE and comorbid psychiatric disorders are prevalent in patients with SLE who attempt suicide. If a rheumatologist suspects that a patient with SLE has a psychiatric disorder, he or she should refer the patient to a psychiatrist. (Psychosomatics 2015; 56:190–195)
INTRODUCTION Suicide is a global health issue, with an estimated burden of 1 million deaths by suicide every year.1 It is well established that mental and physical illnesses are associated with an increased suicide risk.2 Tang and Crane indicated that patients with chronic pain had at least a 2-fold risk of death by suicide.3 Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and its manifestations, such as arthritis, are associated with long-lasting pain.4,5 In addition, many studies have demonstrated an increased prevalence of mental disorders, such as depression and psychosis, in patients with SLE.6,7 These patients are therefore at a risk for suicidal behavior. In a review conducted by Harris and Barraclough, a 4-fold increase in suicide risk was found 190
www.psychosomaticsjournal.org
Received April 13, 2014; revised May 19, 2014; accepted May 19, 2014. From Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC (K-TT, C-WH, T-YH, J-LL, Y-HC, D-YC); School of Medicine, National YangMing University, Taipei, Taiwan, ROC (C-WH, J-LL, Y-HC, D-YC); Division of Immunology and Rheumatology, China Medical University Hospital, Taichung, Taiwan, ROC (J-LL); College of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC (J-LL); Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, ROC (D-YC); Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan, ROC (D-YC). Send correspondence and reprint requests to Der-Yuan Chen, Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Blvd., Taichung 40705, Taiwan, ROC. e-mail: [email protected] & 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Psychosomatics 56:2, March/April 2015
Tang et al. in patients with SLE when compared with the general population.8 However, only a few studies have described suicide attempts in patients with SLE in detail.9,10 The aim of this study is to describe the suicide attempts in patients with SLE in a tertiary hospital in Taiwan. MATERIALS AND METHODS Patients A total of 8 patients with SLE, 7 women and 1 man, with 12 suicide attempts among them were identified among 2469 patients with SLE on regular follow-up at Taichung Veterans General Hospital, a tertiary medical center in Taiwan, from March 1, 2003 to November 30, 2013. A suicide attempt was defined as an act of selfharm with suicidal intent, despite the outcome.11 All the identified patients fulfilled the 1997-revised American College of Rheumatology criteria for SLE.12 Their demographic data, lupus manifestations throughout their disease course, laboratory data, and details of their suicide attempts were retrospectively documented, using a standard data extraction form. This study was performed in compliance with the Declaration of Helsinki, and the Institutional Review Board of Taichung Veterans General Hospital approved the study protocol. Clinical Manifestations of SLE The diagnosis of neuropsychiatric SLE (NPSLE) was based on the clinical judgment of the attending physician and classified according to the 1999 American College of Rheumatology case definitions.13 The presence of antiphospholipid antibodies and antiphospholipid antibody syndrome was defined as in the revised Sapporo classification criteria.14 Disease activity of SLE was assessed by the change in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score.15 However, serologic markers of disease activity in patients with SLE, such as anti–double-stranded DNA antibodies (antidsDNA), complement 3 (C3), and complement (C4), were seldom measured at the time these patients attempted suicides. Therefore, levels of anti-dsDNA, C3, and C4, measured within a month before or after the suicide attempt, were used in SLEDAI scoring instead. A disease flare was defined as greater than a 3-point change in the SLEDAI score.16 An active serology was defined as either a decrease in the levels of C3 or C4 less than the lower limit of the normal range or an Psychosomatics 56:2, March/April 2015
increase in the levels of anti-dsDNA more than the upper limit of the normal range when compared with last test values. Damage accrual of SLE was assessed by the Systemic Lupus International Collaborating Clinics (SLICC) damage index.17 The Charlson comorbidity index (CCI), an index that assesses both the number and severity of 19 comorbid conditions,18 was calculated for each enrolled patient with lupus. All comorbidities included in the CCI were physical disorders except dementia. SLE, as a connective tissue disease, was scored 1 in the CCI, and therefore, the lowest possible score was 1 for all the enrolled patients with SLE. Literature Review We searched the MEDLINE database (National Library of Medicine, Bethesda, MD). Only articles in English that were published before September 2013 were reviewed, and pediatric cases (r16 years old) were excluded. We found 4 articles describing suicide attempts in patients with SLE in detail.9,10,19,20 Demographic data as well as lupus manifestations, laboratory data, and details of suicide attempts in these patients with SLE were extracted from the literature. Statistics Statistical analysis was performed using SPSS software version 15.0 (SPSS Inc., Chicago, IL). Descriptive statistics for the demographic data, laboratory parameters, lupus manifestations, suicide methods, management, and outcomes of the enrolled patients with SLE in our hospital and in the literature were obtained. RESULTS Demographic Data and Clinical Characteristics of Patients With SLE in Our Hospital Who Attempted Suicide In our hospital, 8 of 2469 patients with SLE (0.3%) attempted suicide in the study period. The demographic data and clinical characteristics of our patients with SLE who attempted suicide are illustrated in Table 1. The median age of the patients was 33 years (range: 19–77 years). The median duration of SLE before the suicide attempt was 6 years, and 6 patients (75%) attempted suicide within 10 years of disease onset. Notably, NPSLE developed in 5 (63%) of our patients with SLE before the suicide attempt (acute confusion in patient 1, www.psychosomaticsjournal.org
191
Suicide Attempts in Patients With Systemic Lupus Erythematosus TABLE 1.
Clinical Characteristics of the 12 Suicide Attempts in 8 Patients With SLE in Our Hospital
Patient Age Psychiatric (y)/sex disorders 1 2 3
33/F 77/M 49/F
4
25/F
– – Reactive depression Mental retardation
SLICC CCI Duration from the onset of SLE (y)
25/F
6 7
19/F 32/F
7 7 7 8
39/F
1 4 1
11 3 11
2 2 4
þ þ þ
Insecticide poisoning Overdose of clonazepam Overdose of hypnotics
3
3
7
2
N.A.
Overdose of sulpiride
8
0
þ
1
5
2
þ
Overdose of meloxicam, liquid brown mixture, antiepileptics, and sulpiride Overdose of sertraline and Lexotan
1 1
5 4
0 0
Insecticide poisoning Detergent poisoning
1
4 4 4 7
2 2 0 10
þ þ þ þ
Self-removal of tracheostomy tube Self-removal of tracheostomy tube Jumping from the second floor Jumping from the 12th floor
Reactive 0 depression – 0 Reactive 1 depression
Psychosis
Suicide method Active serology*
0 0 0
4 5
Change in SLEDAI
1
CCI ¼ Charlson comorbidity index; N.A. ¼ not available; NPSLE ¼ neuropsychiatric systemic lupus erythematosus; SLE ¼ systemic lupus erythematosus; SLICC ¼ systemic lupus international collaborating clinics damage index; SLEDAI ¼ systemic lupus erythematosus disease activity index. n
An active serology was defined as, within a month before or after the suicidal attempt, either a decrease in the levels of C3 or C4 to less than the normal range or an increase in the levels of anti-dsDNA to more than the normal range when compared with last test values.
polyneuropathy in patient 2, intracerebral hemorrhage in patient 4, transient ischemic attack in patient 7, and psychosis in patient 8). Of our patients with SLE, 5 (63%) had psychiatric disorders diagnosed by a psychiatrist (depression in 3 patients, psychosis in 1 patient, and mental retardation in 1 patient), although an actual assessment by a qualified mental health professional was not performed in the other 3 patients. Interestingly, among these patients with psychiatric disorders, 4 (80%) had visited a psychiatrist on a regular basis and taken psychotropic medications before the suicide attempt. Mucocutaneous manifestations were present in 7 (88%) of our patients with SLE, but renal manifestations were present in only 2 (25%) of them. Overall, 3 (38%) patients had scores Z1 in the SLICC damage index, and all these patients had neuropsychiatric damage alone. In terms of comorbidities, only 2 patients (25%) scored Z1 in the CCI (4 for patient 2 and 3 for patient 4). Characteristics of Suicide Attempts in Patients With SLE in Our Hospital As illustrated in Table 1, most (67%) of the 12 suicide attempts involved ingestion of a drug or a
192
www.psychosomaticsjournal.org
toxin. Only 1 suicide attempt succeeded (jumping from the 12th floor) and 3 other attempts resulted in long-term sequelae, including esophageal ulcerations due to insecticide ingestion (patient 1), corrosive injury of the esophagus due to detergent ingestion (patient 7), and left calcaneal fracture and L1 spinal compression fracture due to jumping from the second floor (patient 7). A change in the SLEDAI score 4 3, indicating a lupus flare, was demonstrated in 2 (25%) patients with SLE in our hospital who attempted suicide. Serologic markers of lupus activity, examined within a month before or after the suicide attempt, were detected in 7 patients and an active serology was present in 5 (71%) of them. An argument with the family occurred before 3 suicide attempts. Previous suicidal ideation was detected in 4 attempts (33%), which were all made by patient 7. Of our patients with SLE, 2 received psychiatric interventions after the suicide attempt, but the dosage of steroids or immunosuppressants was not increased in any of them. After a median follow-up of 51 months, of 7 patients with SLE in our hospital with nonfatal suicide attempts, 2 (29%) attempted suicide again (patients 4 and 7).
Psychosomatics 56:2, March/April 2015
Tang et al.
TABLE 2. References
MacNeill et al.18 Bonfa et al.19 Matsukawa et al.8 Karrasa et al.9
Patients With SLE in the Literature Who Had Attempted Suicide Patients who had attempted suicide (n)
Number of suicide attempts
Number of Number of suicide completed attempts suicides during active SLE
1
2
1
1
1
41
N.A.
0
7
8
2
4
5
7
2
1
N.A. ¼ not available; SLE ¼ systemic lupus erythematosus.
*
Demographic Data and Clinical Characteristics of Patients With SLE in the Literature Who Had Attempted Suicide After conducting a literature review, we found 14 patients with SLE who had attempted suicide (Table 2). The median age of the patients was 32 years (range: 17–53 years). The median duration of SLE before the suicide attempt was 2.5 years in 5 patients with SLE in a study by Karrasa et al.10 For the other 9 patients with SLE in the literature who had attempted suicide, disease duration before the attempt was within 5 years for all, including 4 attempts at the onset of SLE. NPSLE developed in 10 patients with SLE (71%) who had attempted suicide, though Karrasa et al. regarded depression in all 5 enrolled patients as NPSLE instead of reactive depression.10 As for psychiatric disorders, 10 (71%) patients with SLE in the literature who had attempted suicide had depression, and 4 (29%) patients had psychosis. Disease activity of SLE was assessed in 13 patients who had attempted suicide, and a concurrent disease flare was present in 4 (31%) of them. Previous suicidal ideation was detected in 5 of 18 attempts (28%). Suicide methods were described in 17 suicide attempts. Overall, 7 (41%) attempts involved drug overdose or ingestion of a toxin and 5 attempts (29%) involved jumping from height. Excluding a patient whose outcomes of suicide attempts were not clearly described,21 6 (35%) of the remaining 17 suicide attempts resulted in fatalities. The dosage of steroids or immunosuppressive therapy was increased in 9 (75%)
Psychosomatics 56:2, March/April 2015
of 12 nonfatal suicide attempts, whereas psychotropic medications were prescribed in 6 attempts (50%). Of 11 patients with SLE with nonfatal suicide attempts, 3 (27%) attempted suicide again. DISCUSSION This study described the characteristics of patients with SLE who attempted suicide in a single center. To our best knowledge, this is the largest case series regarding suicide attempts in patients with SLE, which recruited 8 patients with SLE with 12 suicide attempts among them. The clinical data of these patients with SLE, such as the SLEDAI, SLICC, and CCI, were comprehensively collected. We have also conducted a literature review to further investigate this issue. We demonstrated that prior NPSLE and comorbid psychiatric disorders are prevalent in patients with SLE who attempt suicide. Previous psychiatric interventions might reduce lethal suicide attempts in these patients with SLE. Of the patients with SLE in our hospital, 0.3% attempted suicide in the study period, an incidence lower than that reported by Karassa et al.10 However, the study period of the latter study is twice that of ours.10 In addition, lifetime rate of suicide attempt in Taiwan has been shown to be much lower when compared with the other 7 countries in a cross-national comparison study,21 which may also explain this discrepancy. Patients with SLE usually attempted suicides within 10 years of the diagnosis, both in our patients with SLE and in such patients in the literature. Among patients with SLE in our hospital who attempted suicide, we found that 38% had damage resulting from lupus activity (scores Z1 in the SLICC damage index) within a median disease duration of 6 years, which is comparable to that in the general population with SLE, as Mok et al. demonstrated in a cohort study (38% with damage within a mean disease duration of 75 months).22 Conversely, psychiatric disorders were present in 63% of our patients with SLE who attempted suicide, a prevalence higher than that in the general population with SLE.23 The increased prevalence of psychiatric disorders (86%, data not shown), including psychosis (71%) and depression (29%), was also observed in such patients in the literature. Interestingly, NPSLE developed in 63% of patients with SLE in our hospital who attempted suicide and in 71% of such patients in the literature. Such prevalences of NPSLE were higher
www.psychosomaticsjournal.org
193
Suicide Attempts in Patients With Systemic Lupus Erythematosus than that in the general population with SLE (46% according to the revised American College of Rheumatology NPSLE criteria).24 Insomnia and tapering of steroid dose have been reported to be risk factors for suicide attempts in patients with SLE by Matsukawa et al.,9 although this was not found in patients in our hospital who attempted suicide. Most of the patients with SLE in our hospital who attempted suicide used less violent means, perhaps because of the female predominance among patients with SLE.25,26 The risk of suicide completion in patients with SLE in our hospital was 8%, which is comparable to that in the general population (attempted suicides 10 to 40 times more common than completed suicides).27 A somewhat higher risk of suicide completion (35%) in such patients in the literature was demonstrated, although a statistical significance was not achieved (p ¼ 0.187, the Fisher exact test). This discrepancy might be attributable to previous psychiatrist follow-up and psychiatric management among most of our patients with SLE (80%) who had psychiatric disorders, consistent with the finding by Parra Uribe et al. that suicide completers are less likely to have been followed up by a psychiatrist.27 Interestingly, the only 1 patient with SLE in our hospital who completed suicide was a patient with psychosis who had no previous regular psychiatrist follow-up (patient 8). However, it should be noted that patients who make more violent suicide attempts may die before they have the opportunity to be transferred to hospitals and thus may not be included in our hospital-based study. Population-based studies with a large number of patients with SLE who have attempted suicide are needed to elucidate this issue. The neurobiologic basis of suicide has long been the focus of research.28 Should a suicide attempt be regarded as a manifestation of SLE or a psychologic sequela to the physical illness? Overall, 25% of patients with SLE in our hospital who attempted suicide and 31% of such patients in the literature9,10,19,20 had a disease flare at the time of the suicide attempt. We also demonstrated an active serology in 71% of patients with SLE in our hospital who attempted suicide. For comparison, we retrospectively identified another 16 patients with SLE who have been
followed up for at least 6 years in our hospital (13 women and 3 men, median age 36 years). Of them, 7 (44%) had a disease flare and 8 (50%) had an active serology. We observed a lower prevalence of disease flares and a higher prevalence of active serology in patients with SLE who attempted suicide than in the comparison group in our hospital, although statistical significances were not achieved (p ¼ 1.000 and 0.405, the Fisher exact test). In previous studies, Matsukawa et al. found hypocomplementemia in 5 of 6 patients with SLE who had attempted suicide,9 whereas Karrasa et al. noted lymphopenia in 6 of 7 suicide attempts in patients with SLE.10 The significance of these findings remains to be answered. Our study has some limitations. Firstly, our study is hospital-based and patients with SLE who used more lethal suicide methods might not be enrolled. Therefore, the effect of suicide attempts on patients with SLE might be underestimated. However, because of female predominance among patients with SLE25 and lower suicide completion rate in women,27 it is possible that we only missed few cases. Secondly, the sample size in our study is small, making the study result less powerful. Thirdly, this study is retrospective, and as such, it is prone to biases resulting from missing data and incomplete documentation. Finally, 3 patients with SLE who were identified in our hospital have not received a formal assessment by a psychiatrist, and our results may therefore underestimate the prevalences of psychiatric disorders and suicidal ideation before the suicide attempt. In conclusion, our results showed that prior NPSLE and comorbid psychiatric disorders are prevalent in patients with SLE who attempt suicide. If a rheumatologist suspects that a patient with SLE has a psychiatric disorder, he or she should refer the patient to a psychiatrist for interventions. We sincerely thank the Clinical Informatics Research and Development Center of Taichung Veterans General Hospital for providing the clinical data of patients enrolled in the study. Disclosure: This research received grant funding from the Taichung Veterans General Hospital Research Program only. The authors declare that there is no conflict of interests.
References 1. Krug EG, Mercy JA, Dahlberg LL, Zwi AB: The world report on violence and health. Lancet 2002; 360(9339):1083–1088
194
www.psychosomaticsjournal.org
2. Hawton K, van Heeringen K: Suicide. Lancet 2009; 373 (9672):1372–1381
Psychosomatics 56:2, March/April 2015
Tang et al. 3. Tang NK, Crane C: Suicidality in chronic pain: a review of the prevalence, risk factors and psychological links. Psychol Med 2006; 36(5):575–586 4. Schmeding A, Schneider M: Fatigue, health-related quality of life and other patient-reported outcomes in systemic lupus erythematosus. Best Pract Res Clin Rheumatol 2013; 27(3):363–375 5. Waldheim E, Elkan AC, Bergman S, Frostegard J, van Vollenhoven R, Henriksson EW: Extent and characteristics of self-reported pain in patients with systemic lupus erythematosus. Lupus 2013; 22(2):136–143 6. Bachen EA, Chesney MA, Criswell LA: Prevalence of mood and anxiety disorders in women with systemic lupus erythematosus. Arthritis Rheum 2009; 61(6):822–829 7. Pego-Reigosa JM, Isenberg DA: Psychosis due to systemic lupus erythematosus: characteristics and long-term outcome of this rare manifestation of the disease. Rheumatology (Oxford) 2008; 47(10):1498–1502 8. Harris EC, Barraclough BM: Suicide as an outcome for medical disorders. Medicine (Baltimore) 1994; 73(6):281–296 9. Matsukawa Y, Sawada S, Hayama T, Usui H, Horie T: Suicide in patients with systemic lupus erythematosus: a clinical analysis of seven suicidal patients. Lupus 1994; 3(1):31–35 10. Karassa FB, Magliano M, Isenberg DA: Suicide attempts in patients with systemic lupus erythematosus. Ann Rheum Dis 2003; 62(1):58–60 11. Silverman MM, Berman AL, Sanddal ND, O’Carroll PW, Joiner TE: Rebuilding the tower of Babel: a revised nomenclature for the study of suicide and suicidal behaviors. Part 2: suicide-related ideations, communications, and behaviors. Suicide Life Threat Behav 2007; 37(3):264–277 12. Hochberg MC: Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40(9):1725 13. ACR Ad Hoc Committee On Neuropsychiatric Lupus Nomenclature: The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999; 42(4):599–608 14. Miyakis S, Lockshin MD, Atsumi T, et al: International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4(2):295–306 15. Petri M, Kim MY, Kalunian KC, et al: Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005; 353(24):2550–2558
Psychosomatics 56:2, March/April 2015
16. Buyon JP, Petri MA, Kim MY, et al: The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial. Ann Intern Med 2005; 142:953–962 17. Sutton EJ, Davidson JE, Bruce IN: The systemic lupus international collaborating clinics (SLICC) damage index: a systematic literature review. Semin Arthritis Rheum 2013; 43(3):352–361 18. Charlson ME, Pompei P, Ales KL, MacKenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40(5):373–383 19. MacNeill A, Grennan DM, Ward D, Dick WC: Psychiatric problems in systemic lupus erythematosus. Br J Psychiatry 1976; 128:442–445 20. Bonfa E, Golombek SJ, Kaufman LD, et al: Association between lupus psychosis and anti-ribosomal P protein antibodies. N Engl J Med 1987; 317(5): 265–271 21. Weissman MM, Bland RC, Canino GJ, et al: Prevalence of suicide ideation and suicide attempts in nine countries. Psychol Med 1999; 29(1):9–17 22. Mok CC, Ho CT, Wong RW, Lau CS: Damage accrual in southern Chinese patients with systemic lupus erythematosus. J Rheumatol 2003; 30(7):1513–1519 23. Jarpa E, Babul M, Calderon J, et al: Common mental disorders and psychological distress in systemic lupus erythematosus are not associated with disease activity. Lupus 2011; 20(1):58–66 24. Ainiala H, Hietaharju A, Loukkola J, et al: Validity of the new American College of Rheumatology criteria for neuropsychiatric lupus syndromes: a population-based evaluation. Arthritis Rheum 2001; 45(5):419–423 25. Whitacre CC, Reingold SC, O’Looney PA: A gender gap in autoimmunity. Science 1999; 283(5406):1277–1278 26. Denning DG, Conwell Y, King D, Cox C: Method choice, intent, and gender in completed suicide. Suicide Life Threat Behav 2000; 30(3):282–288 27. Parra Uribe I, Blasco-Fontecilla H, García-Parés G, et al: Attempted and completed suicide: not what we expected? J Affect Disord 2013; 150(3):840–846 28. Ernst C, Mechawar N, Turecki G: Suicide neurobiology. Prog Neurobiol 2009; 89(4):315–333
www.psychosomaticsjournal.org
195
