IOM Tackles Standards on Cognition in Depression

Cognitive dysfunction is a neglected aspect of depression, and much work remains to be done before mapping a research path to treat this dimension of the disorder, concluded panelists at an Institute of Medicine workshop February 24 in Washington, D.C.

Aaron Levin

Depression is as much a cognitive as a mood disorder, given the brain regions involved. Many patients who respond to treatment for depression “continue to have subjective complaints and have difficulty returning to their previous level of function,” according to the workshop’s co-chairs, National Institute of Mental Health (NIMH) Director Thomas Insel, M.D., and Thomas Laughren, M.D., director of Laughren Psychopharm Consulting. Laughren formerly worked at the Food and Drug Administration (FDA) as director of the Division of Psychiatry Products in the Office of New Drugs in the Center for Drug Evaluation and Research.

Workshop participants included representatives from NIMH, the FDA, academia, and the pharmaceutical industry.

That eclectic mix began what is likely to be a long-term discussion of cognition’s role in the definition, research, diagnosis, and treatment of depression.

“Cognitive deficits are associated with poor treatment response, noncompliance with antidepressant treatment, increased suicide risk, and poor return to employment,” said Diego Pizzagalli, Ph.D., a professor of psychiatry at Harvard Medical School. “But we see only moderate effect of treatment on cognition, even as depression symptoms abate.”

In addition, both cognition and mood may be independent of functional deficits, Insel noted. “Maybe we should not spend a lot of time on intermediate measures and look more at performance measures like going back to work,” he said.

He pointed out how little is known about cognition and its relationship to depression. Meta-analyses examining the state of the science have been “underwhelming” because they were limited by heterogeneity and highly variable assessments and were not linked to the patients’ functioning, he said.

Current treatment options are inadequate, added Insel in an interview with Psychiatric News after the workshop. But part of the problem in developing new treatments—whether medications, devices, or psychotherapies—is the lack of universally accepted standards of what and how to measure.

Government, industry, academic researchers, and clinicians must settle on common data elements and ways to measure them easily so as to perceive meaningful change. Doing so means deciding which domains of cognition should be measured, which assessments are best for doing so, how they can best be obtained from patients, and what study designs would work best at revealing the answers.

“What’s missing is a framework for having these discussions,” said Laughren. “We need to continue and find one that will lead to something that summarizes where we are, where we could go, and how we will innovate, design trials, and measure outcomes. The drug companies won’t enter the arena without some clarity.”

Someone must ultimately produce a guidance document to provide some structure for continuing the February discussion, Laughren added. That might be the FDA or NIMH but might also be a semi-independent entity like the Measurement and Treatment Research to Improve Cognition in Schizophrenia, an NIMH initiative that a decade ago sought to stimulate the development of medications to improve cognition in schizophrenia.

“So the challenge is to think about mechanisms, but from an explanatory-model perspective, not just looking at symptoms or objective measures of functioning,” said Amit Etkin, M.D., Ph.D., an assistant professor of psychiatry and behavioral sciences at Stanford University. “But ultimately, we also have to ask patients about what they care about changing in their lives.” ■