Navigating the Maze of Treatment-Resistant Depression

September 18, 2017
George I. Papakostas

Path Remains Murky Despite an Abundance of Options

NEW ORLEANS—Clinicians have many options to use for patients with treatment-resistant depression (TRD), and more are on the way. But the correct approach to take is still rarely clear-cut and the need for more research remains, speaker and author George I. Papakostas, MD, said in a lecture at Psych Congress 2017.

It’s a conundrum faced by a wide swath of mental health clinicians. Dr. Papakostas cited a meta-analysis he had published in 2009, which showed that only about half of adults with major depressive disorder (MDD) exhibited clinical response after a single trial of an approved antidepressant.

“That’s, of course, something we know in the clinic,” he said. “Oftentimes, after treating a patient with an antidepressant, we’re going to have to follow up with a number of strategies in order to get them to full remission.”

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There is a significant need for more studies on switching to another antidepressant after a patient fails to have a sufficient response to a first-line medication, said Dr. Papakostas, Scientific Director, Massachusetts General Hospital Clinical Trials Network and Institute, and Associate Professor of Psychiatry, Harvard Medical School, Boston, Massachusetts.

In addition, there have been no high-quality, randomized studies comparing switching antidepressants with adding treatments to them, he said.

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As a result, “the decision of whether to augment or switch is more of a theoretical one, and takes into account different factors as opposed to a data-driven position,” said Dr. Papakostas, who also maintains an active clinical practice in Boston. Those factors include cost, drug interactions, side effects, potential withdrawal, and possible loss of therapeutic benefit if a drug is discontinued.

While augmentation presents some risks (particularly in the elderly) and can result in complicated treatment plans, there are a variety of agents that can be used when an adjunctive approach is chosen.

The most widely studied adjunctive treatment is atypical antipsychotics, which gives them an advantage, Dr. Papakostas said. (He thinks the evidence base of ketamine products eventually will overtake that of the atypicals.)

Research has shown atypicals to be effective as add-on treatments in depression, but they can carry significant side effects, such as weight gain, increased prolactin or lipids, and extrapyramidal symptoms.