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Patients with mental illness face high mortality risk in drug trials

Patients with psychiatric disorders such as schizophrenia, depression and bipolar disorder who participated in clinical drug trials were at a significantly increased risk for death, researchers reported.

"[M]ortality risk is associated with specific psychiatric diagnoses and detectable within relatively short durations of observation, even among relatively physically healthy patients," Arif Khan, MD, of Duke University, and colleagues wrote. "Interestingly, even when suicide deaths are excluded, the natural cause mortality rates in adult patients with schizophrenia, bipolar disorder, or depression still exceeded those in the general population."

To assess the mortality risk among drug trial participants, the researchers analyzed data from FDA Summary Basis of Approval (SBA) reports on drug applications submitted by pharmaceutical companies from 1990 to 2011. Their analysis included 92,542 adult patients who participated in 47 psychopharmacology clinical trials for for the treatment of schizophrenia, depression, bipolar disorder, anxiety disorders or attention-deficit/hyperactivity disorder.

Results suggested that mortality risk was significantly associated with psychiatric diagnosis (P<.001). Schizophrenia carried the greatest risk for death (3.8-fold increase), followed by depression (3.15-fold increase) and bipolar disorder (threefold increase).

Patients with anxiety disorders faced a mortality risk comparable to that of the general population, the researchers said, and no deaths occurred among patients with ADHD.

Suicide accounted for 109 (41.1%) of the 265 deaths that occurred during the clinical drug trials.

Khan and colleagues also found that short- and medium-term exposure to psychotropic agents, including atypical antipsychotic agents, selective serotonin reuptake inhibitors and selective serotonin-nonrepinephrine reuptake inhibitors, did not compound the risk for death.

The researchers said the results should be viewed with caution because FDA SBA reports are used to evaluate the safety and efficacy of psychotropic treatments, and not mortality risk.

"Our results suggest that further detailed analysis of the clinical trial data by the FDA or the pharmaceutical companies is required before any firm conclusions can be drawn," they wrote. "Furthermore, it is desirable to acquire much longer-term data, such as a decade in duration, regarding potential mortality risk when exposed to psychotropic agents based on the findings from the population studies."

Disclosure: See the study for a full list of financial disclosures.