Risk of All-Cause and Suicide Death in Patients With Schizophrenia: An Entire-Population Longitudinal Study in Taiwan

Chih-Ming Cheng, MD; Wen-Han Chang, MSc; Shih-Jen Tsai, MD; Cheng-Ta Li, MD, PhD; Chia-Fen Tsai, MD, PhD; Ya-Mei Bai, MD; Wei-Chen Lin, MD; Tung-Ping Su, MD; Tzeng-Ji Chen, MD; Mu-Hong Chen, MD, PhD

J Clin Psychiatry 2023;84(6):22m14747

ABSTRACT

Background: Schizophrenia increases mortality from all causes and specific causes. Comprehensive research on modifiable risk factors for early mortality from multiple sources is needed.

Methods: Taiwan’s National Health Insurance Research Database, which contains claims data from a lifetime insurance program for the whole population, provided extensive medical inpatient and outpatient data categorized by ICD-9-CM and ICD-10 for this nationwide retrospective longitudinal cohort study. The National Mortality Registry provided data on all-cause, natural, suicide, and accidental deaths. 191,553 patients with schizophrenia and 26,362,448 individuals without schizophrenia were monitored from January 1, 2003, to December 31, 2017. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for mortality risk were calculated using Cox regression models. We compared different mortality risks associated with schizophrenia across age, sex, and Charlson Comorbidity Index (CCI) subgroups.

Results: We found that schizophrenia results in a relatively higher increase in suicidal mortality in those aged ≤ 20 years (aHR = 15.55; 95% CI, 13.95–17.34), and that effect decreased with age. The effect of schizophrenia in female individuals (suicide death: female, aHR = 11.82, 95% CI, 11.21–12.46; male, aHR = 8.11, 95% CI, 7.77–8.47; difference, P < .001) and individuals without comorbidity (natural cause of death, CCI = 0 aHR = 5.94, 95% CI, 5.68–6.22; CCI = 1–2 aHR = 3.62, 95% CI, 3.52–3.73; CCI > 2 aHR = 1.61, 95% CI, 1.58–1.64) led to comparatively higher mortality risks. The effect of schizophrenia in individuals with AIDS (suicide death, aHR = 2.73, 95% CI, 1.70–4.39) resulted in a relatively smaller increase in suicide mortality compared to individuals with other comorbidities; however, in patients with connective tissue diseases, a diagnosis of schizophrenia still leads to an alarming increase in natural and unnatural mortality.

Conclusions: Schizophrenia in combination with younger age, female sex, comorbid connective tissue disease, or major organ problems necessitates more tailored countermeasures to lessen the higher mortality risk in these patients compared with patients who have these characteristics and conditions but do not have schizophrenia.

J Clin Psychiatry 2023;84(6):22m14747

Author affiliations are listed at the end of this article.

Continue Reading...

Did you know members enjoy unlimited free PDF downloads as part of their subscription? Subscribe today for instant access to this article and our entire library in your preferred format. Alternatively, you can purchase the PDF of this article individually.

Subscribe Now

Already a member? Login

Purchase PDF for $40

Members enjoy free PDF downloads on all articles. Join today

References (49)

Laursen TM, Plana-Ripoll O, Andersen PK, et al. Cause-specific life years lost among persons diagnosed with schizophrenia: is it getting better or worse? Schizophr Res. 2019;206:284–290. PubMed CrossRef
Tanskanen A, Tiihonen J, Taipale H. Mortality in schizophrenia: 30-year nationwide follow-up study. Acta Psychiatr Scand. 2018;138(6):492–499. PubMed CrossRef
Hjorthøj C, Stürup AE, McGrath JJ, et al. Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis. Lancet Psychiatry. 2017;4(4):295–301. PubMed CrossRef
Crump C, Winkleby MA, Sundquist K, et al. Comorbidities and mortality in persons with schizophrenia: a Swedish national cohort study. Am J Psychiatry. 2013;170(3):324–333. PubMed CrossRef
Høye A, Jacobsen BK, Hansen V. Increasing mortality in schizophrenia: are women at particular risk? a follow-up of 1111 patients admitted during 1980–2006 in Northern Norway. Schizophr Res. 2011;132(2-3):228–232. PubMed CrossRef
Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry. 2007;64(10):1123–1131. PubMed CrossRef
Chen WJ, Huang YJ, Yeh LL, et al. Excess mortality of psychiatric inpatients in Taiwan. Psychiatry Res. 1996;62(3):239–250. PubMed CrossRef
Pan YJ, Yeh LL, Chan HY, et al. Excess mortality and shortened life expectancy in people with major mental illnesses in Taiwan. Epidemiol Psychiatr Sci. 2020;29:e156. PubMed CrossRef
Walker ER, McGee RE, Druss BG. Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. JAMA Psychiatry. 2015;72(4):334–341. PubMed CrossRef
Dickerson F, Origoni A, Schroeder J, et al. Mortality in schizophrenia and bipolar disorder: clinical and serological predictors. Schizophr Res. 2016;170(1):177–183. PubMed CrossRef
Laursen TM, Nordentoft M, Mortensen PB. Excess early mortality in schizophrenia. Annu Rev Clin Psychol. 2014;10(1):425–448. PubMed CrossRef
Dipasquale S, Pariante CM, Dazzan P, et al. The dietary pattern of patients with schizophrenia: a systematic review. J Psychiatr Res. 2013;47(2):197–207. PubMed CrossRef
Fleury MJ, Grenier G, Bamvita JM, et al. Professional service utilisation among patients with severe mental disorders. BMC Health Serv Res. 2010;10(1):141. PubMed CrossRef
Cradock-O’Leary J, Young AS, Yano EM, et al. Use of general medical services by VA patients with psychiatric disorders. Psychiatr Serv. 2002;53(7):874–878. PubMed CrossRef
Huang MH, Chen MH, Huang KL, et al. Increased risk of type 2 diabetes among the siblings of patients with schizophrenia. CNS Spectr. 2019;24(4):453–459. PubMed CrossRef
Ringen PA, Engh JA, Birkenaes AB, et al. Increased mortality in schizophrenia due to cardiovascular disease: a non-systematic review of epidemiology, possible causes, and interventions. Front Psychiatry. 2014;5:137. PubMed CrossRef
Bai YM, Su TP, Chen MH, et al. Risk of developing diabetes mellitus and hyperlipidemia among patients with bipolar disorder, major depressive disorder, and schizophrenia: a 10-year nationwide population-based prospective cohort study. J Affect Disord. 2013;150(1):57–62. PubMed CrossRef
Harris LW, Guest PC, Wayland MT, et al. Schizophrenia: metabolic aspects of aetiology, diagnosis and future treatment strategies. Psychoneuroendocrinology. 2013;38(6):752–766. PubMed CrossRef
Nielsen RE, Uggerby AS, Jensen SO, et al. Increasing mortality gap for patients diagnosed with schizophrenia over the last three decades: a Danish nationwide study from 1980 to 2010. Schizophr Res. 2013;146(1-3):22–27. PubMed CrossRef
Dickerson F, Origoni A, Rowe K, et al. Risk factors for natural cause mortality in a cohort of 1494 persons with serious mental illness. Psychiatry Res. 2021;298:113755. PubMed CrossRef
Berardi D, Stivanello E, Chierzi F, et al. Mortality in mental health patients of the Emilia-Romagna region of Italy: a registry-based study. Psychiatry Res. 2021;296:113702. PubMed CrossRef
Das-Munshi J, Chang CK, Dutta R, et al. Ethnicity and excess mortality in severe mental illness: a cohort study. Lancet Psychiatry. 2017;4(5):389–399. PubMed CrossRef
Brown S, Kim M, Mitchell C, et al. Twenty-five year mortality of a community cohort with schizophrenia. Br J Psychiatry. 2010;196(2):116–121. PubMed CrossRef
Erlangsen A, Andersen PK, Toender A, et al. Cause-specific life-years lost in people with mental disorders: a nationwide, register-based cohort study. Lancet Psychiatry. 2017;4(12):937–945. PubMed CrossRef
Olfson M, Gerhard T, Huang C, et al. Premature mortality among adults with schizophrenia in the United States. JAMA Psychiatry. 2015;72(12):1172–1181. PubMed CrossRef
Pelton M, Ciarletta M, Wisnousky H, et al. Rates and risk factors for suicidal ideation, suicide attempts and suicide deaths in persons with HIV: a systematic review and meta-analysis. Gen Psychiatr. 2021;34(2):e100247. PubMed CrossRef
Wang CC, Shao CH, Li HJ, et al. Profiles and persistence of initial antiretroviral therapy among HIV infected patients in Taiwan: a nationwide population-based cross-sectional study from 2011 to 2017. J Microbiol Immunol Infect. 2022;55(5):838–844. PubMed CrossRef
de los Rios P, Okoli C, Punekar Y, et al. Prevalence, determinants, and impact of suboptimal adherence to HIV medication in 25 countries. Prev Med. 2020;139:106182. PubMed CrossRef
Lee CY, Jen IA, Lan YC, et al. AIDS incidence trends at presentation and during follow-up among HIV-at-risk populations: a 15-year nationwide cohort study in Taiwan. BMC Public Health. 2018;18(1):589. PubMed CrossRef
Closson K, McLinden T, Patterson TL, et al; Comparative Outcomes And Service Utilization Trends (COAST) Study. HIV, schizophrenia, and all-cause mortality: a population-based cohort study of individuals accessing universal medical care from 1998 to 2012 in British Columbia, Canada. Schizophr Res. 2019;209:198–205. PubMed CrossRef
Quan H, Sundararajan V, Halfon P, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43(11):1130–1139. PubMed CrossRef
Shinozaki T, Mansournia MA, Matsuyama Y. On hazard ratio estimators by proportional hazards models in matched-pair cohort studies: emerging themes in epidemiology. 2017;14(1):6.
Correll CU, Solmi M, Croatto G, et al. Mortality in people with schizophrenia: a systematic review and meta-analysis of relative risk and aggravating or attenuating factors. World Psychiatry. 2022;21(2):248–271. PubMed CrossRef
Haas AD, Ruffieux Y, van den Heuvel LL, et al; IeDEA Southern Africa collaboration. Excess mortality associated with mental illness in people living with HIV in Cape Town, South Africa: a cohort study using linked electronic health records. Lancet Glob Health. 2020;8(10):e1326–e1334. PubMed CrossRef
GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry. 2022;9(2):137–150. PubMed CrossRef
Carlborg A, Winnerbäck K, Jönsson EG, et al. Suicide in schizophrenia. Expert Rev Neurother. 2010;10(7):1153–1164. PubMed CrossRef
Sher L, Kahn RS. Suicide in schizophrenia: an educational overview. Medicina (Kaunas). 2019;55(7):361. PubMed
Thara R, Kamath S. Women and schizophrenia. Indian J Psychiatry. 2015;57(suppl 2):S246–S251. PubMed CrossRef
Laursen TM, Munk-Olsen T, Gasse C. Chronic somatic comorbidity and excess mortality due to natural causes in persons with schizophrenia or bipolar affective disorder. PLoS One. 2011;6(9):e24597. PubMed CrossRef
Sun D, Li L, Zhang X, et al. Causes of sudden unexpected death in schizophrenia patients: a forensic autopsy population study. Am J Forensic Med Pathol. 2019;40(4):312–317. PubMed CrossRef
Mirza RA, Eick-Cost A, Otto JL. The risk of mental health disorders among US military personnel infected with human immunodeficiency virus, active component, US Armed Forces, 2000–2011. MSMR. 2012;19(5):10–13. PubMed
Helleberg M, Pedersen MG, Pedersen CB, et al. Associations between HIV and schizophrenia and their effect on HIV treatment outcomes: a nationwide population-based cohort study in Denmark. Lancet HIV. 2015;2(8):e344–e350. PubMed CrossRef
Wang LY, Chen SF, Chiang JH, et al. Autoimmune diseases are associated with an increased risk of schizophrenia: a nationwide population-based cohort study. Schizophr Res. 2018;202:297–302. PubMed CrossRef
Benros ME, Pedersen MG, Rasmussen H, et al. A nationwide study on the risk of autoimmune diseases in individuals with a personal or a family history of schizophrenia and related psychosis. Am J Psychiatry. 2014;171(2):218–226. PubMed CrossRef
Garen T, Lerang K, Hoffmann-Vold AM, et al. Mortality and causes of death across the systemic connective tissue diseases and the primary systemic vasculitides. Rheumatology (Oxford). 2019;58(2):313–320. PubMed CrossRef
Parperis K, Kyriakou A, Voskarides K, et al. Suicidal behavior in patients with systematic lupus erythematosus: systematic literature review and genetic linkage disequilibrium analysis. Semin Arthritis Rheum. 2022;54:151997. PubMed CrossRef
Crump C, Sundquist K, Winkleby MA, et al. Mental disorders and risk of accidental death. Br J Psychiatry. 2013;203(4):297–302. PubMed CrossRef
Hellemose LAA, Laursen TM, Larsen JT, et al. Accidental deaths among persons with schizophrenia: a nationwide population-based cohort study. Schizophr Res. 2018;199:149–153. PubMed CrossRef
Bohnert AS, Ilgen MA, Ignacio RV, et al. Risk of death from accidental overdose associated with psychiatric and substance use disorders. Am J Psychiatry. 2012;169(1):64–70. PubMed CrossRef