Psychotropics Lower, Don't Raise, Mortality in Psych Patients

Fran Lowry

August 29, 2013

Severe psychiatric illness, especially schizophrenia and major depression, are associated with an increased risk for death, but the newer agents prescribed to treat these illnesses appear to reduce this risk, new research suggests.

The results, from an analysis of US Food and Drug Administration (FDA) Summary Basis of Approval (SBA) reports comprising more than 92,000 patients with psychiatric illness, should be very reassuring to clinicians, Arif Khan, MD, from Northwest Clinical Research Center, Bellevue, Washington, told Medscape Medical News.

"Our study confirms that certain psychiatric illnesses, in particular schizophrenia and major depressive disorder, do come with an increased risk of death," said Dr. Khan. "But it also shows that pharmacotherapy with serotonin reuptake inhibitors, and other psychotropic drugs, is very effective in reducing that risk."

The study was published online August 28 in JAMA Psychiatry.

Illness-Related Mortality

It has been known since the 1920s that mental illness is associated with a risk for early death. More recently, with the advent of psychopharmacology, some investigators have been concerned that psychotropic drugs may make patients sicker and cause death.

Dr. Arif Khan

"We wanted to investigate and verify these assumptions," Dr. Khan said. "There are very good statistical models that we can use now, clinical trials give good quality data, and the FDA SBA reports are very thorough. Until 1976, those reports used to be confidential, but now with the Freedom of Information Act, the data have become public, and we can access it."

The investigators collected all of the mortality data from the SBA reports for new drug approvals for 28 psychopharmacologic drugs between 1990 and 2011.

A total of 92,542 patients with schizophrenia, depression, bipolar disorder, anxiety disorders, or attention-deficit/hyperactivity disorder (ADHD) participated in the clinical trials.

The researchers found that overall, patients with a psychiatric diagnosis had a significantly higher risk for death compared with the general population (P < .001).

Patients with schizophrenia had the highest risk for death, with a 3.8-fold increase compared with the general adult population. Patients with major depression had a 3.15-fold increased risk for death, and those with bipolar disorder had a 3.0-fold increased risk.

In all, there were 265 deaths, and 109 (41.1%) were from suicide.

Fears Quelled

There was no increased risk for death among patients with anxiety or ADHD diagnoses. The mortality risk among patients with anxiety disorders (222 per 100,000 patient exposure years; 95% confidence interval, 28 - 416) was similar to that in the general population in the year 2000, and there were no deaths in the 3 programs that included adult patients with ADHD.

Even after taking out the risk associated with suicide, the increased early death risk or shortened life span was 2-fold higher among patients with schizophrenia and major mood disorders compared with the general population, mainly because of myocardial infarction, strokes, and similar illnesses.

"This shortening of life span or an increase in early death could not be fully accounted for by poor medical care or ongoing severe medical illnesses, as such patients were not included in these research trials, and good-quality medical care was provided during trial participation," Dr. Khan said.

"It is likely that these psychiatric illnesses are associated with inherent risk of brain, heart, and other organ abnormalities and thus carry serious risk of early death such as the risk seen in patients with high blood pressure or high cholesterol," he said.

Treatment with psychotropic drugs did not increase mortality, as had been feared, Dr. Khan said.

The overall mortality was lower among patients with schizophrenia assigned to antipsychotic agents, including haloperidol and modern atypical antipsychotics, compared with patients with schizophrenia assigned to placebo. The same result held true for patients with depression and bipolar disorder who were randomly assigned to active drug vs placebo.

In all, treatment with modern psychotropic drugs decreased mortality risk by 25% to 70%.

"The old class of drugs, like Elavil and Tofranil, increased mortality risk compared with placebo, but all of the others that we use now, like Zoloft, Depakote, they all reduced mortality risk compared to placebo," Dr. Khan said.

"This was contrary to our expectations. At least short-term exposure to these modern psychotropic agents for up to 3 or 4 months does not increase mortality risk. The reason for such a finding is unknown at present," he added.

"These medicines are very positive, people should take them, and physicians should feel reassured they have a positive effect. This is not just an imagined effect. It is real."

Mitigates Risk

Jeffrey Lieberman, MD, professor and chairman of psychiatry at Columbia University, New York, New York, agrees with this view.

Dr. Jeffrey Lieberman

Describing the study as "very important," Dr. Lieberman told Medscape Medical News that the study refutes prior reports that psychotropic drugs are harmful.

"It is well known that people with specific forms of mental illness have a markedly increased rate of mortality or decreased survival than do individuals who don't have these mental illnesses. This particularly pertains to schizophrenia, bipolar disorder, and depression, and this study replicates the finding from prior reports," he said.

"In addition, the study also disabuses inaccurate notions of psychotropic medicines that say that while these drugs may be therapeutic against mental symptoms they are also dangerous or produce adverse effects that are harmful from a medical standpoint," Dr. Lieberman said.

"These findings show that the psychotropic drugs, whether they are antipsychotic drugs, mood stabilizers, or serotonin reuptake inhibitor antidepressants, do not contribute to increased mortality, in fact they mitigate that."

Showing that psychotropic drugs are in fact beneficial carries the implication that it is the illness itself and the lifestyle that it leads people into, which are the primary risk factors for the increased mortality, increased medical morbidity, and risk for suicide, Dr. Lieberman said.

"Treatment, while it may have side effects, has a net benefit to people by mitigating their illness and protecting them from the lifestyle patterns that incur increased morbidity and mortality and prevent people who are potentially inclined to suicide from acting on those inclinations."

Dr. Khan is founder and director of Columbia Northwest Pharmaceuticals LLC. Dr. Lieberman has disclosed no relevant financial relationships.

JAMA Psychiatry. Published online August 28, 2013 Abstract

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