Increased mortality in schizophrenia ‘not attributable to drug therapy’

Sep 4 2013

By Joanna Lyford, Senior medwireNews Reporter

The increased mortality risk observed among patients with severe psychiatric illness, including schizophrenia, does not seem to be attributable to use of psychopharmacologic therapy, study findings indicate.

“Contrary to expectations, the mortality risk is not increased with short-and medium-term exposure to modern psychotropic agents, such as atypical antipsychotics or antidepressants,” state Arif Khan (Duke University School of Medicine, Durham, North Carolina, USA)) and co-authors in JAMA Psychiatry.

Khan’s team used the Freedom of Information Act to obtain data from the US Food and Drug Administration on the safety and efficacy of 43 psychopharmacologic agents approved between 1990 and 2011.

These “Summary Basis of Approval” reports include data on 92,542 patients who participated in placebo-controlled trials and safety extension studies of treatments for schizophrenia, depression, bipolar disorder, anxiety disorders, and attention-deficit/hyperactivity disorder (ADHD).

The total exposure period for psychotropic agents was 23,711 years and 2183 years for placebo. Overall mortality risk in the study population was high, with suicides accounting for 41.1% of the 265 deaths.

Mortality risk was strongly associated with psychiatric diagnosis, report Khan et al. Compared with the general population, mortality was increased 3.8-fold in patients with schizophrenia, 3.2-fold in those with depression, and threefold in those with bipolar disorder.

Mortality was not increased in patients with anxiety disorders, however, and there were no deaths among those with ADHD.

Importantly, Khan’s team found that in patients with schizophrenia, overall mortality was lower among those treated with antipsychotic agents than in those given placebo.

A similar pattern was seen in patients with bipolar disorder while in patients with depression or anxiety disorders there was no difference in mortality between the active therapy and placebo groups.

The exception was patients with depression, in whom mortality was higher in those given tricyclic or tetracyclic antidepressants than in those given placebo. The actual numbers were too small for statistical analysis, however.

Khan et al say that their study suggests that short- and medium-term exposure to modern psychotropic agents does not increase mortality risk; however, they call for further detailed analysis of the data before drawing firm conclusions.

“To obtain definitive results, prospectively designed studies are required,” they conclude. “Given the magnitude of excess mortality risk associated with some of the psychiatric diagnoses, such studies are essential both for evaluating mortality risk and for designing methods or treatments to reduce it.”

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