Excess mortality in patients with schizophrenia spectrum disorders in Malaga (Spain): A cohort study

Abstract

Introduction

In general, mental disorders are strongly associated with premature mortality worldwide (Walker et al., 2015) and remain an important global health problem (Liu et al., 2017). Among them, excess mortality in schizophrenia spectrum disorders is a major public health concern that causes significant suffering in patients, families and society. Reviews of the literature on mortality in schizophrenia and psychotic disorders have found a standardised mortality ratio (SMR) of 2–4 (Saha et al., 2007; McGrath et al., 2008; Ringen et al., 2014; Piotrowski et al., 2017). A recent meta-analysis by Oakley et al. (2018) found a gender-pooled SMR of 3.08 for schizophrenia and psychotic disorders in the community. Likewise, a recent systematic review (Hjorthøj et al., 2017) found 14.5 potential years of life lost (YLL) associated with schizophrenia, with an overall weighted average life expectancy of 64.7 years, being lower for men (59.9 years) than for women (67.6 years).

Mortality in schizophrenia is associated with natural causes, mainly cardiovascular diseases (Brown et al., 2010; Bushe et al., 2010), cardiometabolic adverse events related to anti-psychotic medication (Mitchell et al., 2013) and other physical health comorbidities such as cancer (Crump et al., 2013; Laursen et al., 2014; Morgan et al., 2014). Among the unnatural causes of death, suicide is the most common (Rantanen et al., 2009; Brown et al., 2010; Laursen et al., 2014). Concerning sociodemographic factors, living in areas of socioeconomic disadvantage has been associated with higher mortality rates (Tsai et al., 2014).

In addition, the excess mortality found in schizophrenia spectrum disorders does not seem to be diminishing with the advances in diagnostic and therapeutic methods; instead, it is increasing (McGrath et al., 2008; Oakley et al., 2018). Although mortality has declined for the general population, people with schizophrenia spectrum disorders still have elevated mortality (Ösby et al., 2016; Westman et al., 2018). Lee et al. (2018) found that the SMR increased by 37% from pre-1970 to post-1970 studies and Bushe et al. (2010) found a peak in the mid-1990s. Therefore, as a public concern, excess mortality in schizophrenia remains a phenomenon that is insufficiently studied and unsolved (Piotrowski et al., 2017) and analyses have shown high levels of heterogeneity between regions.

Furthermore, there is a lack of studies in southern and eastern Europe on mortality in schizophrenia spectrum disorders (Gondek et al., 2015) and the study of possible regional differences could be informative and valuable (Galletly, 2017). The scarcity of studies in these regions makes it difficult to assess the longitudinal evolution of mortality in schizophrenia spectrum disorders in a large part of Europe and also to explore more about the different sociodemographic factors that could be influencing the so-called mortality gap. In Spain, there has been one published study estimating the characteristics of physical disease in hospitalised patients with schizophrenia, which concluded that physical disease in schizophrenia was associated with an SMR of 3.6 (Bouza et al., 2010). In order to evaluate the mortality in schizophrenia and related disorders, we have carried out this study based on data from a well-defined catchment area in southern Spain where a comprehensive case register operating since 2003 was developed. Hence, the purpose of the present study is to present mortality data in a cohort of patients with schizophrenia spectrum disorders in Malaga (Spain); specifically, the causes of mortality, SMR, life expectancy, YLL and possible sociodemographic factors associated with mortality were analysed.

Methods

Results

In this study, 1418 patients were included. Briefly, cases were more frequently male (63.90%), middle-aged (average: 42.31; s.d.: 13.63), single (61.35%), with no formal education or primary education only (64.53%), living with their family of origin/other relatives (48.02%) and receiving welfare benefits mainly due to their severe mental illness (41.60%). Most of the cohort lives in non-deprived urban areas (72%). The majority had a diagnosis of schizophrenia (60.08%). Table 1 shows the demographic characteristics and diagnoses of the sample at baseline, the number of events (deaths), person-years of follow-up and mortality rates.

Discussion

The main finding of this study was the corroboration of a mortality gap in patients with schizophrenia spectrum disorder compared with the general population in a wide catchment area of Spain and the association of mortality with socioeconomic disadvantages. To the best of our knowledge, this is the first study in Spain to calculate mortality indexes using a population-based register from mental health services (including mainly community care-based users and in-patients). Importantly, the study was carried out in a population in which there was a lack of information on a fundamental issue such as the mortality of patients with schizophrenia spectrum disorders in a population where the mental health care services are less developed than in the countries where mortality has been studied.

Our results indicate that the SMR was 3.189 in the cohort and 3.997 in the sample of individuals diagnosed with schizophrenia, with both values being higher than in the meta-analysis of Oakley et al. (2018), which found an SMR of 3.085 in schizophrenia spectrum disorders and 3.103 for studies that only included schizophrenia. The YLL found in our study was more than 5 years higher in comparison with a meta-analysis by Hjorthøj et al. (2017) in which the YLL was 14.5. However, despite the YLL and SMR indicating higher relative mortality in our cohort, life expectancy was higher in comparison with the value of 64.7 years reported by Hjorthøj et al. (2017). This apparently contradictory result could be explained by Spain having one of the most long-lived populations in the world and corroborates the mortality gap in schizophrenia in southern Spain, confirming that this population does not benefit completely from the health improvements that have occurred in our context in recent decades. Nevertheless, these results need to be replicated in extended studies. Regarding results in nearby countries, a study in France found an SMR that was very similar to that of our study (Tran et al., 2009), but another study in northern Italy found a lower SMR (2.17) in a population with schizophrenia (Grigoletti et al., 2009). The difference in SMR in the present study in comparison with the Italian study is relevant and might be explained by the limited sample size of the Italian study (4613 person-years) and the differences in socioeconomic variables between regions. It is also important to highlight that the mortality gap is higher in the younger population. Thus, one of the most concerning outcomes is that the SMR is more than nine times higher than in the general population at younger ages of 15–29 years and seven times higher at ages of 30–44 years. This could be explained by the high mortality due to suicide in the young population with schizophrenia spectrum disorders among other factors. In fact, another important result in our study is that the SMR of suicide (22.18) was higher in comparison with other studies; for example, a meta-analysis of ten studies found an SMR of 12.86 (Saha et al., 2007) and highlighted the need to improve treatments to prevent suicides in our environment. This elevated SMR may be influenced by the lower rates of suicide and suicidal behaviour in southern European regions, including Spain, compared with other countries in northern Europe (Castillejos et al., 2020). Further studies in our area are needed to explore this issue in more depth. Our study also shows that the mortality gap is higher in men than in women, as found by other studies (Laursen, 2011; Crump et al., 2013; Nielsen et al., 2013; Lesage et al., 2015).

Regarding natural causes of death, in accordance with our results, other studies have found that cardiovascular disease is the main cause of mortality (Ösby et al., 2016; Westman et al., 2018), highlighting the necessity to reduce cardiovascular risk in this population. Studies carried out in Spain on the physical health of a population with severe mental disorders show a high prevalence of risk factors of mortality: metabolic syndrome, tobacco consumption and unhealthy lifestyle behaviours (Manzanares et al., 2014; Fernández Guijarro et al., 2020). In general, schizophrenia spectrum disorders have been associated with unhealthy lifestyles that have a negative impact on health and also reduce access to healthcare (Kurdyak et al., 2012; Tsai et al., 2014; Jayatilleke et al., 2017; Gur et al., 2018). Likewise, results from a Spanish consensus on the physical health of patients with schizophrenia concluded that an awareness of several aspects of the physical health of this population should be increased among primary healthcare providers and specialists (Sáiz Ruiz et al., 2008). Concerning non-natural causes of mortality, suicide was the most frequent (13.09%) and the first cause of mortality among patients <35 years old. Our results are in accordance with those of Alaräisänen et al. (2009), who analysed a cohort of patients with schizophrenia, following them from 16 to 39 years and found that half of the cause of death was suicide. Likewise, Palmer et al. (2005) found that the suicide rate was higher in a first-episode cohort than in those followed-up later during their illness.

After controlling by confounders, several sociodemographic variables were associated with mortality: age, gender, type of area of residence and receiving welfare benefits (compared with employed status). Interestingly, our study found a relationship between mortality and participants who lived in disadvantaged socioeconomic areas. This finding is consistent with some studies suggesting that socioeconomic inequalities influence mortality and morbidity in schizophrenia spectrum disorders (Kisely et al., 2007; Burns et al., 2014). Unfavourable socioeconomic conditions are frequent in populations with serious mental illness and could affect the course of the mental disorder and influence the mortality gap (Muntaner et al., 2004). Also, medical advances and improvements in healthcare, which have turned illnesses that were fatal into chronic diseases, have had no relevant impact on specific subgroups, including persons with schizophrenia (Lee et al., 2018). Lee et al. (2018) suggest a parallel between socially or economically disadvantaged segments of the general population and people with schizophrenia concerning mortality gap. It is important to highlight the potential role of the recession in the results of this study as the economic crisis resulted in increased unemployment, poverty and inequality in Spain from 2008. Another important consequence of the recession was the reduction in mental health services in the catchment area (Moreno-Küstner and Masedo Gutierrez, 2017). Future studies are necessary to analyse these issues in more depth.

Finally, we found that participants receiving welfare benefits had increased mortality compared with employed participants. It is possible that receiving welfare benefits is associated with more frequent physical illnesses and higher severity of the disorder. It would be relevant to study whether employment promotion might be beneficial in preventing early mortality in this population. In summary, in accordance with Galletly (2017), socioeconomic factors cannot be ignored in the analysis of mortality outcomes.

Conclusions and clinical implications

In summary, this study showed that individuals suffering from schizophrenia spectrum disorders had higher mortality than the general population. The study provides detailed information about mortality: the SMR was more than 3, the YLL was more than 20 and life expectancy at birth was 67.11 years. Finally, several characteristics, such as age, being male, living in socioeconomically deprived urban areas and receiving welfare benefits, were associated with mortality.

Our results imply that urgent studies are required in Spain and southern Europe to determine factors associated with premature mortality in schizophrenia spectrum disorders and how they might be reduced in our environment. Future studies should explore the relative contribution to the mortality of, for example, medication and substance use, among others. Our findings support the necessity to implement strategies to improve the healthcare of this population and increase efforts to prevent suicide. Actions directed to improving living conditions, socioeconomic integration and the quality of health services could be beneficial in reducing mortality.

Acknowledgements

Financial support

Fermin Mayoral Cleries and Jose Guzman-Parra have received funding from the Andalusia Government in the grants for human resources reinforcement in the research activity (Acción A de intesificación 2017 and Acción B de refuerzos de larga duración 2014). Berta Moreno Küstner has received funding from the Andalusian Government (P10-CTS-5862), and from the Ministry of Health (Ministry of Health, Social Services and Equality, Spain (Grant: PI16/00647) and co-founded by European Regional Development Fund (FEDER)

Ethical standards

This study was approved by the Provincial Ethics Committee of Research of Malaga and by the University of Malaga's Ethics Committee. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000.

References