Total and cause-specific standardized mortality ratios in patients with schizophrenia and/or substance use disorder

Individuals with schizophrenia have a two- to three-fold increased mortality compared to the general population [1–3] and a 10-20-year reduction in average life span [2, 4–6]. Individuals with substance use disorder (SUD) have an even higher risk of premature death, ranging from a four-fold increased mortality among persons with alcohol use disorder (AUD) [7–10] to a four to-15-fold increased mortality among opioid users [11–13]. A concurrent diagnosis of schizophrenia spectrum disorder (SCZ) and SUD (henceforth referred to as SCZ+SUD) is associated with a variety of detrimental outcomes, among these increased somatic morbidity [14–19], increased risk of fatal overdoses, violent behavior [20–23] and victimization [24, 25]. Despite these vulnerabilities and a high [26, 27], and probably increasing [28], prevalence of comorbid SUD in SCZ patients, the mortality in the comorbid group has been less studied and with contrasting results. Studies of SCZ individuals with co-morbid SUD have found both increased [29–34] and decreased [35] all-cause mortality, increased suicide mortality [36, 37], but no difference in cardiovascular mortality [38] compared to SCZ individuals without SUD. Studies of SUD individuals report both higher [39, 40], similar [12, 13, 40–43], and lower [44] mortality in individuals also diagnosed with a psychotic disorder, compared to individuals with SUD-only, depending on type of SUD and gender [40]. Only a few studies with complete national coverage have investigated all cause [30, 33, 34, 40] or cause-specific mortality [33, 34] in patients with SCZ-only, SUD-only or co-morbid SCZ and SUD, and neither of these reported results for different age groups or mortality from unnatural causes of death. Introduction: The aims of the present study were to (i) investigate standardized mortality ratios for all cause mortality (SMRs) in patients with SCZ, SCZ-only, SUD-only and SCZ+SUD, diagnosed in Norwegian psychiatric or somatic specialist health care, (ii) describe how much of the excess mortality that could be attributed to a concurrent diagnosis of SCZ and SUD, and (iii) investigate age-, sex-, and cause-specific SMRs in patients with SCZ-only, SUD-only or SCZ+SUD. We hypothesized that mortality in patients with SCZ and/or SUD would be increased compared to the general population for all main causes of death, and that patients with a concurrent diagnosis of SCZ and SUD would have particularly high SMRs.Individuals with schizophrenia or substance use disorder have a substantially increased mortality compared to the general population. Despite a high and probably increasing prevalence of comorbid substance use disorder in people with schizophrenia, the mortality in the comorbid group has been less studied and with contrasting results. We performed a nationwide open cohort study from 2009 to 2015, including all Norwegians aged 20–79 with schizophrenia and/or substance use disorder registered in any specialized health care setting in Norway, a total of 125,744 individuals. There were 12,318 deaths in the cohort, and total, sex-, age- and cause-specific standardized mortality ratios (SMRs) were calculated, comparing the number of deaths in patients with schizophrenia, schizophrenia only, substance use disorder only or a co-occurring diagnosis of schizophrenia and substance use disorder to the number expected if the patients had the age-, sex- and calendar-year specific death rates of the general population. The SMRs were 4.9 (95% CI 4.7–5.1) for all schizophrenia patients, 4.4 (95% CI 4.2–4.6) in patients with schizophrenia without substance use disorder, 6.6 (95% CI 6.5–6.8) in patients with substance use disorder only, and 7.4 (95% CI 7.0–8.2) in patients with both schizophrenia and substance use disorder. The SMRs were elevated in both genders, in all age groups and for all considered causes of death, and most so in the youngest. Approximately 27% of the excess mortality in all patients with schizophrenia was due to the raised mortality in the subgroup with comorbid SUD. The increased mortality in patients with schizophrenia and/or substance use disorder corresponded to more than 10,000 premature deaths, which constituted 84% of all deaths in the cohort. The persistent mortality gap highlights the importance of securing systematic screening and proper access to somatic health care, and a more effective prevention of premature death from external causes in this group.The study is funded by a research grant offered by the Regional Health Authorities in Northern Norway. Grant number: PFP1236-15. URL: https://helse-nord.no/. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.publishedVersio