4 December 2007. It comes as no surprise that people with schizophrenia tend to die sooner than those without it, but a meta-analysis of 37 research papers from 25 nations shows that the mortality difference between the two groups has burgeoned in recent decades. This alarming finding comes from a report in the October Archives of General Psychiatry by John McGrath and others at the Queensland Centre for Mental Health Research in Brisbane, Australia. Although suicide deaths garner most of the research attention, the researchers write, “Less widely appreciated is the fact that people with schizophrenia are at increased risk for premature death associated with comorbid somatic conditions.”
To compare death rates in two populations, researchers often compute the standardized mortality ratio, or SMR. In this context, they divide the number of deaths observed in subjects with schizophrenia by the number expected in an age- and sex-matched cohort from the general population. Two earlier meta-analyses—one based on studies published between 1969 and 1996 (Brown, 1997), the other on studies from 1973 to 1995 (Harris and Barraclough, 1998)—found an SMR of 1.5 to 1.6, meaning that people with schizophrenia are about one and a half times more likely than the general population to die during a given period.
It may not be a coincidence that the later review found a greater risk. A Swedish study published after the prior meta-analyses revealed that the added death risk associated with schizophrenia rose from 1976 to 1995. In the one meta-analysis that explored time trends, the mortality gap widened from the 1970s to the 1980s, although it narrowed in the 1990s. Since those decades brought stepped-up efforts to treat mental illness, along with the introduction of second-generation antipsychotic drugs, McGrath and colleagues wanted to clarify whether the death disparity has worsened.
To do so, McGrath, first author Sukanta Saha, and David Chant conducted a meta-analysis of studies released between 1980 and early 2006 that examined mortality in schizophrenia. The studies came from countries at various stages of economic development; they spanned the globe from North and South America to Europe, Australia, and Asia. Overall, the studies furnished information on 22,296 deaths.
McGrath and his collaborators zeroed in on research reports that gave either the SMR or the data needed to compute it. When possible, they also determined the annual all-cause case fatality rate, or CFR. The CFR indicates the percentage of persons diagnosed with a particular illness who died during a given time frame.
Not just suicide, but physical diseases, too
In comparing cohorts with schizophrenia to the general population, the analysis found an all-cause SMR of 2.58, consistent with the 2006 review. When Saha and colleagues looked at the studies’ follow-up dates, they found a significant rise in the SMRs, from 1.84 in the 1970s, to 2.98 in the 1980s, and even 3.20 in the 1990s. They note that this trend runs counter to the decline in age-standardized mortality rates seen in the general population of most nations. Since CFRs stayed constant, “These findings suggest that people with schizophrenia have not fully benefited from the improvements in health outcomes available to the general population,” they write.
As for causes of death, subjects with schizophrenia were eight times more likely than others to die of unnatural causes such as homicide, suicide, and accidents. Indeed, they were 12 times more likely to die by suicide. These numbers, although tragic, belie the fact that natural causes such as heart disease kill the majority of people with schizophrenia, who are twice as likely as those in the larger community to die of natural causes.
That excess death risk extended to all categories of disease except cerebrovascular diseases. The highest median SMRs occurred for infectious (4.29), nervous (4.22), genitourinary (3.70), and respiratory disease (3.19). The median SMR for deaths due to cardiovascular disease, a top cause of death in many countries, was 1.79, and from endocrine disease, 2.63.
What’s going on?
Saha and colleagues did not probe the reasons for the widening mortality gap, but they hint that second-generation antipsychotic drugs may further amplify the differences (see SRF related news stories on heart disease, glucose metabolism, and weight gain). They note, “Compared with typical antipsychotics, several of the second-generation antipsychotics are more likely to cause weight gain and metabolic syndrome,” two big risk factors for death across all causes and particularly from heart disease. In fact, the National Hospital Discharge Survey found that the prevalence of diabetes in people with schizophrenia versus those without mental illness soared, after a lag period, following the debut of atypical antipsychotics. Because these risk factors may take decades to steal a life, the authors warn that the future may bring an even grimmer reality.
“Apart from adverse effects related to medication, schizophrenia can trigger a cascade of socioeconomic and lifestyle factors that, in turn, can translate into adverse physical health outcomes,” Saha and colleagues write. For instance, people with schizophrenia tend to receive inadequate care for their physical health needs and to engage in unhealthy behaviors such as smoking. Furthermore, the same environmental and genetic factors that may foster schizophrenia could contribute to other medical problems.
This meta-analysis shows the need for more research to find ways to prevent suicide by people with schizophrenia, as well as to pinpoint the causes of the added risk of somatic illness that also threatens their lives. As Saha and colleagues write, “Given the potential for an even greater disease burden as a result of the introduction of second-generation antipsychotic medications, research aimed at optimizing the physical health of people with schizophrenia needs to be undertaken with a sense of urgency.”—Victoria L. Wilcox.
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 Oct; 64(10):1123-1131. Abstract