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Mandate to Assess Suicide Risk in Drug Trials

The Food and Drug Administration (FDA) has asked pharmaceutical companies to collect data on psychiatric side effects encountered in clinical trials or to retrospectively re-analyze adverse effects on a case-by-case basis.

The New York Times had reported in January that all pharmaceutical companies would be required to submit clinical trial data on suicidal risk and ideation. Neurology Today contacted the FDA for clarification of the policy.

The request is not a formal policy change, said Crystal Rice, of the FDA Center for Drug Evaluation and Research, and the agency is not requiring this information for new drug applications. But it is asking some manufacturers to cull the data on a case-by-case basis with certain drug classes — such as antidepressants, obesity drugs, or anti-seizure drugs — that might have an associated risk for suicide.

Several leading neurology investigators agreed that the FDA's proactive stance is proper, and that suicide risk should be assessed in treatment trials involving people who may be depressed, psychotic, or have some other affective disorder. Murray Grossman, MD, associate professor of neurology at the Hospital of the University of Pennsylvania, whose research on language and communicative processing in patients with Alzheimer disease (AD) and Parkinson disease (PD), as well as early diagnosis in frontotemporal dementia, includes a clinical assessment of suicide risk in his studies.

Daniel Weintraub, MD, assistant professor of psychiatry and neurology at the University of Pennsylvania and a consultant psychiatrist for the Parkinson's Disease Centers at the Philadelphia Veterans Affairs Medical Center and the University of Pennsylvania, who studies psychiatric and cognitive complications of PD and AD, also assesses scales to evaluate the risk for ideation for suicide or death.

“I think any trial involving a CNS-active drug should include an assessment for suicidal or death behaviors and ideation,” Dr. Weintraub said. He noted that psychiatric and cognitive complications in patients with neurological conditions have long been under-recognized, adding that physicians should routinely screen for depression, anxiety, psychosis, and cognitive impairment. “It is not sufficient to rely on adverse event reporting to ascertain these signs and symptoms.”

“The risk of untreated depression is far greater than any potential side effects of antidepressants, and the same case may be able to be made for all classes of psychiatric drugs, “ Dr. Weintraub continued. “But those decisions need to be made after weighing the potential risks and benefits for each individual patient.”

Dr. Grossman emphasized the difficulty of predicting accurately for suicide risk. “Some suicides occur without any apparent warning at all,” he said.

“The research suggesting a slight increase in risk of suicidal and death behaviors and ideation from a range of medications, both psychiatric and non-psychiatric, only highlights the importance of screening for psychiatric and cognitive complications,” Dr. Weintraub said.

The latest FDA safety step follows several developments that began with the 2004 FDA black box warning stamped on all antidepressants that warns of increased suicidality in children and adolescents, a case which exemplified the fact that many drugs are not tested for subtle behavioral changes, which might cause development of psychiatric side effects like heightened suicidal ideation and urges.