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A New Generation of Depression Treatment Approaches

December 19, 2018
Michael Thase, MD

Emerging Therapies Could Address Unmet Needs In Patients

Since Michael Thase, MD, became a psychiatrist in 1983, the landscape of depression treatments and approaches has changed dramatically.

The tricyclic antidepressants and monoamine oxidase inhibitors of the early 1980s were followed by selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, first-generation antipsychotics, and modern forms of psychotherapy.

In the early 2000s, a few successful monoamine- targeted antidepressants emerged. But after that, activity in the field dwindled, said Dr. Thase, Professor of Psychiatry, Perelman School of Medicine, University of Pennsylvania, and Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania.

“None of the potentially exciting newgeneration treatments that were being researched at that time came to fruition as antidepressants,” he said, noting that many large pharmaceutical companies moved away from research and development of antidepressants after major trials failed. “No new truly different antidepressants came out for over a decade.”

Simultaneously, about 12 years ago, the first reports began to emerge about ketamine. Dr. Thase was skeptical about it then. But today he is optimistic about what ketamine—and other emerging psychiatric medications with new mechanisms of action—may mean for the future of mental health treatment.

“There’s just more and more evidence that although ketamine itself may ultimately not be the way forward, the way it engages a different receptor system in the brain is truly different than the old monoamine reuptake inhibitors,” he said. “So that does create the excitement of a new way forward.”

Dr. Thase reviewed data on some of those emerging medications, outlined the pathophysiology of depression, and discussed the limitations of available treatments at a session at Psych Congress 2018.

“There’s clearly not a sense that we’ve won, that we’ve got all that we need,” he said. “One out of 3 people who begin treatment don’t achieve, ultimately, the goal of having a full and sustained remission, and that’s an unacceptably high failure rate given all the ways that depression can complicate or potentially even ruin your life or lead to suicide.”

Dr. Thase believes that esketamine, a stereoisomer of ketamine which is administered intranasally, will likely be approved by the US Food and Drug Administration (FDA) in 2019. And he wouldn’t be surprised if, one day, ketamine programs can be found at most major treatment centers, as electroconvulsive therapy (ECT) and neuromodulation programs are.

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