Schizophrenia Diagnosis Associated With Higher Mortality Rate

WACOL, Australia, Oct 5-Schizophrenia leads to an age-related mortality rate that is about 2.5 times that of the general population, and the difference appears to be increasing, researchers here reported.

Suicide, which was more than 12 times more likely among people with schizophrenia, was the leading cause-specific mortality risk, John McGrath, MD, PhD, of the Park Center for Mental Health, and colleagues, reported in the October issue of Archives of General Psychiatry.

The investigators examined the standardized mortality ratios (SMRs), which were calculated by dividing the observed mortality reported in 37 schizophrenia studies by the expected mortality rates as predicted by age and sex in the general population. The studies, conducted in 25 countries, were published from January 1, 1980, through January 31, 2006.

The SMRs were derived from an estimated total of 22,296 discrete deaths reported in the 37 studies.

Among those with schizophrenia, the median SMR for suicide was 12.86. The next most common cause-specific SMR was infectious diseases (4.29), followed by nervous diseases (4.22), genitourinary diseases (3.70), respiratory diseases (3.19), endocrine diseases (2.68), and digestive diseases (2.38).

Strokes were unlikely to be a cause of death, with a median SMR of 0.69 for cerebrovascular disease. Cancer was not a leading cause of death (SMR 1.37 for neoplastic diseases). The authors said the SMR for neoplastic diseases confirmed reports from linkage studies that have “suggested that cancers may be significantly less prevalent in people with schizophrenia.”

The investigators wrote that the introduction of the second-generation of atypical antipsychotic medications, which were initially “found to be associated with better quality of life and reduced risk of relapse,” may be a factor in mortality because more recent studies linked the drugs to weight gain and metabolic syndrome.

The metabolic syndrome is associated with a 3-fold increase in cardiovascular mortality and a 2-fold increase in all-cause mortality.

But, the investigators were “unable to explore the role of atypical medications as a contributing factor” for the increasing mortality because it may take decades for those data to emerge. Studies undertaken in 1990s, which were the most recent included in the review, “would capture only a small facture of the eventual burden of mortality” associated with drugs associated with obesity and metabolic syndrome, they wrote.

But the clock was ticking for second-generation atypicals and the authors suggested that the use of those medications was likely to contribute to “an even greater disease burden” in coming decades.

The investigators found that the relative risk for mortality associated with schizophrenia was greatest in developed countries, where the median standardized mortality ratio was 2.79, vs 2.19 in emerging nations, and 2.02 in the least developed nations. But they urged caution with this observation because only 3 studies had data from the least developed and emerging nations. Moreover, “a single derived variable was used to define economic status.”

The authors said a number of factors appear to contribute to increased mortality, including the relatively early onset of illness-usually in late teens or early 20s-that “can result in a cascade of unhealthy lifestyle factors that elevate the risk of various somatic diseases and consequently increase the risk of death.”

For example, those with schizophrenia are thought to be less likely to seek health care and to use prescribed medicines, and more likely to engage in high-risk behaviors.

The authors also speculated that there might be genetic factors, such a link between schizophrenia and diabetes, that have not yet been elucidated.

As delivery of health services to the general population improves and mortality rates from a number of conditions continues to decline, the mortality gap between patients with schizophrenia and healthy adults is likely to increase, the authors wrote. “Research aimed at optimizing the physical health of people with schizophrenia needs to be undertaken with a sense of urgency,” they concluded.