People with mental illness have significantly higher mortality rates compared to the general population. The elevated mortality spans all causes of death, age groups, and diagnostic subgroups, but it is particularly high for those with severe mental disorders. Deaths from unnatural causes such as suicides and accidents are high, but the majority of life years lost are due to somatic diseases, particularly cardiometabolic and respiratory diseases. Mortality is a long-term outcome measure, and addressing it requires complex actions. Optimal treatment of the mental disorder is crucial; an integrated focus on physical and mental health, along with tailored screening and treatment for established somatic diseases, are just some of the components of this large puzzle. Overall, this issue concerns equity in healthcare more than equality, implying that both resources and efforts must be more extensive than in the general population to achieve a comparable result.
The increased mortality in persons with severe mental illness compared to the rest of the population has been consistently reported by in studies spanning from nearly 100 years ago (1, 2) to recent decades (3, 4), and it does not seem to have improved. The World Health Organization (WHO) and others have highlighted the increasing burden of disease caused by mental illness (5, 6). Additionally, the Lancet Psychiatry Commission has described the drastically high mortality among individuals with mental illness, as well as the personal, social, and economic challenges associated with mental illness throughout the lifespan (7). In all mortality studies, including those focusing on individuals with mental illness and other subgroups, it is crucial to consider the baseline mortality rate of the general population, which can vary between countries and complicate international comparisons. This also underscores the importance of accounting for covariates such as gender, age, and socioeconomic factors.
Severe mental illness (SMI) refers to psychological problems of such a debilitating nature that they severely impair a person’s ability to engage in functional and occupational activities (8). The definition of severe mental disorders (SMD), however, varies somewhat among authors. Severe mental disorders typically includes conditions such as moderate to severe depression, bipolar disorder, and schizophrenia and other psychotic disorders, as defined by the WHO (5). Other definitions apply criteria of severity, duration and dysfunction (9). The observed increased mortality is most prominent for severe mental disorders as defined by the WHO, but it is also evident in other groups, such as patients with severe eating disorders, severe personality disorders, or substance use disorders (3, 10-15).
In 2015, Walker ER et al conducted a systematic meta-analysis and review of 203 studies from 29 countries (10). These studies employed a variety of methods, including calculation of standardized mortality ratios, relative risks, hazard ratios, odds ratios, and years of potential life lost, to estimate the mortality differences between people with mental illness and the general population. Their inclusion criteria were broad and encompassed less severe mental illness such as anxiety. Despite this, the median potential life years lost was 10 years, and mental disorders were estimated to account for 14.3 % of deaths worldwide, or approximately 8 million deaths each year. People with mental disorders have a 2.22 times higher all-cause relative mortality risk than the general population (RR, 95% CI 2.12 – 2.33), the highest all-cause mortality was observed in patients with psychoses (RR=2.54, 95% CI 2.35 - 2.75). Among the severe mental disorders, schizophrenia is the diagnostic group associated with the highest rates of premature deaths compared to the general population, with more than 20 life years lost and a particularly high mortality in younger age groups (16), followed by mood disorders and bipolar disorder (17). The high mortality for schizophrenia is shown throughout the world, with a similar pattern of elevated mortality due to natural causes in all countries studied (18). However, there are significant regional differences related to cause-specific and suicide-related mortality.
Unnatural deaths
The high mortality can arise from unnatural causes of deaths, such as suicide or accidents, or from natural causes. Compared to the general population the rates of unnatural deaths are very high, and the association between suicide and mental disorders and substance use disorders is well documented (19). Also, mental disorders are shown to be strong, independent risk factors for accidents (20), with or without substance use. The review by Ali et al concludes that for schizophrenia, there is an almost nine times higher relative risk to die from unnatural causes compared to the general population, for bipolar disorder the risk is even higher; ten times higher risk compared to the general population (4). The suicide risk is particularly high in younger age groups and during the first years after diagnosis, with an increased risk during admission or shortly after discharge (21).
Natural deaths
However, the majority of excess deaths and life years lost are still attributed to natural causes among people with severe mental disorders. For schizophrenia, mortality rates are elevated for all causes of death, and across all age and sex groups. Mortality due to natural causes is almost three times higher than in the general population for both sexes (RR=2.89 at a mean age of 53 years, 95% CI 2.50 – 3.34). Somatic multimorbidity affects the mortality (22). Similar to the general population, cardiovascular diseases (CVDs) are the leading cause of death also in persons with severe mental illness. However, the rates are more than doubled compared to the general population, with a relative risk of 2.13 (95% CI 1.01 – 4.49). The relative risk for respiratory diseases compared to the general population is also very high; 4.26 (95% CI 3.89 - 4.66) (4). The mortality in schizophrenia is higher in younger age groups, and higher in men. The pattern concerning mortality is similar for bipolar disorders, though slightly lower (except from unnatural causes). For both sexes, the relative risk for patients with bipolar disorder compared to the general population is 2.99 for respiratory diseases (95% CI 2.33 – 3.84) and 2.00 for CVD (95% CI 1.67 – 2.38). Some studies report higher overall mortality in women with bipolar disorder than on men, whereas others report no differences.
Mortality due to cancer is also somewhat elevated, but less so than for CVD and respiratory diseases. The relative risk for schizophrenia and bipolar disorder is 1.76 (95% CI 1.24 – 2.51), and 1.15 (95% CI 1.02 -1.29), respectively. The pattern related to cancer subgroups is more complex, with somewhat conflicting results in different studies (17). Additionally, there is the paradox where cancer incidence does not appear to be elevated, yet cancer mortality is. This consistent reporting of higher cancer fatality rates in cancer concurrent with a schizophrenia diagnosis could be due to several factors, such as lower access to health care, poor adherence to treatment, smoking, or comorbidity issues.
The high mortality rate has been emphatically established in numerous review articles in recent years, and many reports and action plans emphasize the importance of preventive and treatment measures to reduce mortality and improve physical health among individuals with severe mental disorders.
Why is the morbidity and mortality so high?
To explore the possible causes of high morbidity and mortality, as well as potential measures to improve the situation, is akin to trying to solve a vast jigsaw puzzle. The explanation does not lie in one definite cause, nor does it have a single solution. The relationship between mental illness and somatic disease is also bidirectional; individuals with mental illness have a higher risk of developing physical diseases, and conversely, the presence of physical diseases can increase the risk of developing mental illness. Additionally, the risk of suicide increases with both mental and physical illnesses. Therefore, improving physical health may indirectly help reduce suicide rates.
The high mortality rate is of course closely linked to increased morbidity, as demonstrated by the significantly higher incidence of CVDs, such as coronary heart disease and congestive heart failure, among individuals with schizophrenia compared to the general population (23). Furthermore, two to four times higher rates of diabetes, metabolic syndrome, dyslipidemia and hypertension is observed in numerous studies, and is also estimated as higher in younger age groups than in the general population (24). Accordingly, a significantly increased cardiometabolic morbidity is observed also in individuals with bipolar disorder or depression, compared to the general population. Very high prevalence of chronic obstructive pulmonary disease (COPD) is also reported (25). Severe anxiety disorders and experiences of persistent or intense stress, or posttraumatic stress disorder, also seem to be independently associated with an increased CVD risk (26).
Genetic overlap
Some pieces of the puzzle emerge from genetic studies that report a genetic overlap between schizophrenia and CVD risk factors, such as type 2 diabetes, systolic and diastolic blood pressure, blood lipids, body mass index, and waist-to-hip ratio (27, 28). However, the genetic influences of psychiatric illnesses on an increasing range of human traits and diseases are extremely complex. This complexity is further compounded by the clinical and genetic heterogeneity and overlap between mental disorders.
Environmental risk factors
Other pieces of the puzzle relate to biological, neurohormonal, behavioural and psychological factors (26), which are again linked to the well-known higher prevalence of CVD risk factors (26). The biological mechanisms suggested to be involved in the relationship between mental illness and CVDs have included autonomic nervous system dysfunction, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, oxidative stress, increased platelet activity, and inflammation. Inflammation is of particular interest, as it might be a shared etiological factor for both mental illness and CVD; inflammatory biomarkers known to predict CVD and cardiovascular events have also been demonstrated in severe mental disorders such as schizophrenia and bipolar disorder.
One of the most important and prevalent behavioural risk factors is smoking (7). People with severe mental illness exhibit a much higher prevalence of smoking compared to the general population, and those who smoke generally consume more nicotine than smokers without mental illness. Additionally, sedentary behaviour and poor nutrition are significantly more prevalent among persons with mental illness. Moreover, comorbid substance use disorder has consistently been reported to increase all-cause mortality (16). The prevalence of substance use is high in people with severe mental illness and is itself a risk factor for CVD.
Allostatic load
Other risk factors stem from the complex interplay among experienced adverse childhood experiences, allostatic load (described as “the cost of chronic exposure to fluctuating or heightened neural or neuroendocrine response resulting from repeated or chronic environmental challenge that an individual reacts to as being particularly stressful related to stress”(29)), low socioeconomic status, and a higher prevalence of somatic diseases and unfavourable health outcomes in adulthood. This is discussed in an intriguing review by Misiak et al from 2022 (30), which suggests an overall lasting impact on biological dysregulation in adult life due to heightened psychosocial stress and adverse experiences early in life. However, the possible mediating and moderating processes are complex, and specific disease outcomes remain unclear.
Antipsychotics
Furthermore, it has been questioned whether treatment with antipsychotic medication actually increases morbidity and mortality. Despite the well-known cardiometabolic side effects and weight gain associated with antipsychotics, the review by Correll et al from 2022 summarizes that antipsychotics were found to be protective against all-cause and natural cause-related mortality compared to no use of antipsychotics (16). The largest effect was observed for second-generation antipsychotics. However, first generation antipsychotics used by patients with incident schizophrenia were associated with increased mortality due to suicides and natural causes.
Treatment disparities
There is compelling evidence that people with severe mental illness, particularly those with schizophrenia, receive less frequent screening and lower-quality treatment than the general population for both cardiometabolic diseases and cancer (31, 32). The reasons for these disparities are multifaceted. They may originate from factors related to the structural characteristics of the healthcare system, including a lack of targeted and continuous cooperation between somatic and mental healthcare, insufficient focus on and knowledge about somatic disorders within mental healthcare, or correspondingly limited knowledge about severe mental illness in somatic healthcare. Additionally, several patient-related factors associated with mental symptoms may exacerbate these disparities; psychotic symptoms, social withdrawal, or impairments related to social functioning or cognition can reduce the ability to recognize or interpret symptoms or seek help. This may be further impaired by previous negative experiences with healthcare. Nonadherence to treatment, particularly complex treatment procedures, socioeconomic factors, and a lack of social network or family support add to this complexity. Moreover, there is a lack of financial and professional incentives aimed at the comprehensive treatment of complex issues such as somatic screening and treatment for patients with severe mental illness. Many consider it time-consuming and challenging, which may further increase stigma and barriers to offering screening and treatment. A kind of "negative pragmatism" may also deepen this stigma; based on the underlying assumption that the patient has a chronically impaired quality of life and therefore will not benefit from or have the ability to, for example, quit smoking, reduce weight, or engage in physical activity.
"The mortality rate is significantly higher among those with mental disorders compared to the general population, especially for those with severe mental disorders."
Is it changing?
As mentioned above, the mortality rate among individuals with mental illness must be compared to that of the general population. Over the last few decades, general mortality from cardiovascular diseases has decreased in the general population due to improved treatments and behavioural changes such as dietary modifications and smoking cessation. However, this decline is not observed among individuals with severe mental illness; in fact, the rate ratio of CVD-related mortality has almost doubled since the 1990s, particularly in younger age groups (33). A Danish study reported a slight increase in expected life years in the overall group with mental illness, but this was not the case for severe mental disorders such as schizophrenia or substance use disorders (34). In other words, the somatic health benefits seen in the general population in most countries are not reflected in the group of people with severe mental illness. Service improvements may have somewhat reduced the overall risk of suicides and accidents among people with severe mental illness over the last few decades in several countries, whereas the life years lost due to somatic diseases have in fact increased. The result is a persisting and even widening mortality gap.
Summary
Most individuals with mental illness do not die directly from the illness, but from associated factors. The mortality rate is significantly higher among those with mental disorders compared to the general population, especially for those with severe mental disorders. Deaths from unnatural causes such as suicides and accidents are notably higher, but the majority of life years lost are due to somatic diseases, particularly cardiometabolic and respiratory diseases. The high mortality rate has been emphatically established in numerous review articles in recent years, and many reports and action plans emphasize the importance of preventive and treatment measures to reduce mortality and improve physical health among individuals with severe mental disorders. Although the efforts so far have not shown very encouraging results, mortality is a long-term outcome measure, and both the causes and measures to reduce it require complex actions and increased healthcare resources. Optimal treatment of the mental disorder is crucial. Furthermore, an integrated focus on physical and mental health, and tailored screening and treatment for established somatic diseases are just some of the pieces in this large puzzle. Overall, this concerns equity in healthcare more than equality; implying that both resources and efforts must be more extensive than in the general population for a comparable result to be achieved. □
References by request
Malzberg B. Mortality in involution melancholia. The American journal of psychiatry. 1937;93(5):1231-8.
ØDegard Ø. Mortality in Norwegian mental hospitals 1926-1941. Acta Genet Stat Med. 1951;2(2):141-73.
Plana-Ripoll O, Musliner KL, Dalsgaard S, Momen NC, Weye N, Christensen MK, et al. Nature and prevalence of combinations of mental disorders and their association with excess mortality in a population-based cohort study. World psychiatry : official journal of the World Psychiatric Association (WPA). 2020;19(3):339-49.
Ali S, Santomauro D, Ferrari AJ, Charlson F. Excess mortality in severe mental disorders: A systematic review and meta-regression. Journal of psychiatric research. 2022;149:97-105.
Comprehensive Mental Health Action Plan 2013-2030. Geneva: World Health Organization; 2021. Report No.: 9789240031029.
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. The lancet Psychiatry. 2022;9(2):137-50.
Firth J, Siddiqi N, Koyanagi A, Siskind D, Rosenbaum S, Galletly C, et al. The Lancet Psychiatry Commission: a blueprint for protecting physical health in people with mental illness. The lancet Psychiatry. 2019;6(8):675-712.
Network NMHI. Severe mental illness (SMI) and physical health inequalities: briefing. Public Health England; 2018.
Ruggeri M, Leese M, Thornicroft G, Bisoffi G, Tansella M. Definition and prevalence of severe and persistent mental illness. The British journal of psychiatry : the journal of mental science. 2000;177:149-55.
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):334-41.
van Hoeken D, Hoek HW. Review of the burden of eating disorders: mortality, disability, costs, quality of life, and family burden. Current opinion in psychiatry. 2020;33(6):521-7.
Tiosano S, Laur L, Tirosh A, Furer A, Afek A, Fink N, et al. Personality disorders and cause-specific mortality: a nationwide study of 2 million adolescents. Psychological medicine. 2022;52(9):1746-54.
Høye A, Jacobsen BK, Bramness JG, Nesvåg R, Reichborn-Kjennerud T, Heiberg I. Total and cause-specific mortality in patients with personality disorders: the association between comorbid severe mental illness and substance use disorders. Social psychiatry and psychiatric epidemiology. 2021;56(10):1809-19.
Solmi M, Monaco F, Højlund M, Monteleone AM, Trott M, Firth J, et al. Outcomes in people with eating disorders: a transdiagnostic and disorder-specific systematic review, meta-analysis and multivariable meta-regression analysis. World psychiatry : official journal of the World Psychiatric Association (WPA). 2024;23(1):124-38.
Aldridge RW, Story A, Hwang SW, Nordentoft M, Luchenski SA, Hartwell G, et al. Morbidity and mortality in homeless individuals, prisoners, sex workers, and individuals with substance use disorders in high-income countries: a systematic review and meta-analysis. Lancet (London, England). 2018;391(10117):241-50.
Correll CU, Solmi M, Croatto G, Schneider LK, Rohani-Montez SC, Fairley L, et al. Mortality in people with schizophrenia: a systematic review and meta-analysis of relative risk and aggravating or attenuating factors. World psychiatry : official journal of the World Psychiatric Association (WPA). 2022;21(2):248-71.
Biazus TB, Beraldi GH, Tokeshi L, Rotenberg LS, Dragioti E, Carvalho AF, et al. All-cause and cause-specific mortality among people with bipolar disorder: a large-scale systematic review and meta-analysis. Molecular psychiatry. 2023;28(6):2508-24.
Solmi M, Croatto G, Fornaro M, Schneider LK, Rohani-Montez SC, Fairley L, et al. Regional differences in mortality risk and in attenuating or aggravating factors in schizophrenia: A systematic review and meta-analysis. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2024;80:55-69.
Ferrari AJ, Norman RE, Freedman G, Baxter AJ, Pirkis JE, Harris MG, et al. The burden attributable to mental and substance use disorders as risk factors for suicide: findings from the Global Burden of Disease Study 2010. PloS one. 2014;9(4):e91936.
Crump C, Sundquist K, Winkleby MA, Sundquist J. Mental disorders and risk of accidental death. The British journal of psychiatry : the journal of mental science. 2013;203(3):297-302.
Nordentoft M, Wahlbeck K, Hallgren J, Westman J, Osby U, Alinaghizadeh H, et al. Excess mortality, causes of death and life expectancy in 270,770 patients with recent onset of mental disorders in Denmark, Finland and Sweden. PloS one. 2013;8(1):e55176.
Kugathasan P, Stubbs B, Aagaard J, Jensen SE, Munk Laursen T, Nielsen RE. Increased mortality from somatic multimorbidity in patients with schizophrenia: a Danish nationwide cohort study. Acta psychiatrica Scandinavica. 2019;140(4):340-8.
Correll CU, Solmi M, Veronese N, Bortolato B, Rosson S, Santonastaso P, et al. Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large-scale meta-analysis of 3,211,768 patients and 113,383,368 controls. World psychiatry : official journal of the World Psychiatric Association (WPA). 2017;16(2):163-80.
Goldfarb M, De Hert M, Detraux J, Di Palo K, Munir H, Music S, et al. Severe Mental Illness and Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022;80(9):918-33.
Jaén-Moreno MJ, Rico-Villademoros F, Ruiz-Rull C, Laguna-Muñoz D, Del Pozo GI, Sarramea F. A Systematic Review on the Association between Schizophrenia and Bipolar Disorder with Chronic Obstructive Pulmonary Disease. Copd. 2023;20(1):31-43.
De Hert M, Detraux J, Vancampfort D. The intriguing relationship between coronary heart disease and mental disorders. Dialogues in clinical neuroscience. 2018;20(1):31-40.
Andreassen OA, Djurovic S, Thompson WK, Schork AJ, Kendler KS, O'Donovan MC, et al. Improved detection of common variants associated with schizophrenia by leveraging pleiotropy with cardiovascular-disease risk factors. American journal of human genetics. 2013;92(2):197-209.
Andreassen OA, Hindley GFL, Frei O, Smeland OB. New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications. World psychiatry : official journal of the World Psychiatric Association (WPA). 2023;22(1):4-24.
McEwen BS, Stellar E. Stress and the individual. Mechanisms leading to disease. Arch Intern Med. 1993;153(18):2093-101.
Misiak B, Stańczykiewicz B, Pawlak A, Szewczuk-Bogusławska M, Samochowiec J, Samochowiec A, et al. Adverse childhood experiences and low socioeconomic status with respect to allostatic load in adulthood: A systematic review. Psychoneuroendocrinology. 2022;136:105602.
Solmi M, Fiedorowicz J, Poddighe L, Delogu M, Miola A, Høye A, et al. Disparities in Screening and Treatment of Cardiovascular Diseases in Patients With Mental Disorders Across the World: Systematic Review and Meta-Analysis of 47 Observational Studies. The American journal of psychiatry. 2021;178(9):793-803.
Solmi M, Firth J, Miola A, Fornaro M, Frison E, Fusar-Poli P, et al. Disparities in cancer screening in people with mental illness across the world versus the general population: prevalence and comparative meta-analysis including 4 717 839 people. The lancet Psychiatry. 2020;7(1):52-63.
Lambert AM, Parretti HM, Pearce E, Price MJ, Riley M, Ryan R, et al. Temporal trends in associations between severe mental illness and risk of cardiovascular disease: A systematic review and meta-analysis. PLoS Med. 2022;19(4):e1003960.
Plana-Ripoll O, Weye N, Momen NC, Christensen MK, Iburg KM, Laursen TM, McGrath JJ. Changes Over Time in the Differential Mortality Gap in Individuals With Mental Disorders. JAMA psychiatry. 2020;77(6):648-50.