FDA approves first fast-acting oral drug for clinical depression

A newly approved drug from Axsome Therapeutics, Auvelity, can improve symptoms of major depressive disorder (MDD) — also known as clinical depression — after one week of administration, making it the first and only oral rapid-acting drug approved for the disorder. 

The drug’s mechanism is also novel and marks the first new type of medication to be approved for the condition in 60 years. Auvelity was granted Breakthrough Therapy Designation following a priority review by the Food and Drug Administration (FDA).

The announcement comes on the heels of a new review that found serotonin levels or activity are likely not the cause of depression, challenging a long-held belief the condition is the result of brain chemical imbalances and opening a window for new research on different potential treatments. 

Common medicines on the market for those with MDD include selective serotonin reuptake inhibitors (SSRIs), such as Zoloft, and serotonin-norepinephrine reuptake inhibitors (SNRIs), like Cymbalta, for example, among others. 

Trial results showed the positive benefits of Auvelity, an N-methyl D-aspartate (NMDA) receptor antagonist, were sustained at all time points assessed, although its exact mechanism of action in MDD remains unclear. It will become available to patients in the fourth quarter of 2022.

“The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile,” said Maurizio Fava of Massachusetts General Hospital in a press release. Fava is also a Slater Family professor of psychiatry at Harvard Medical School.

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The treatment comes at an opportune time as many Americans continue to suffer poor mental health outcomes resulting from the COVID-19 pandemic. 

Prior to COVID-19, “over 20 million American adults experienced major depressive disorder each year,” said Michael Pollock, Chief Executive Officer of the Depression and Bipolar Support Alliance, in the release.

But research from Brown University, published in October 2021, found depression rates tripled during the first year of COVID-19 alone, while recent economic woes, global conflict and a contentious political landscape, coupled with a shortage of mental health care providers, can all compound poor outcomes. 

“Nearly two thirds of patients treated with currently available antidepressants do not adequately respond, and those that do may not achieve clinically meaningful responses for up to six to eight weeks,” Fava said. “Given the debilitating nature of depression, the efficacy of Auvelity observed at one week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition.”

The FDA approval is based on a clinical trial program that tested the medication in more than 1,100 adults with depression. In addition to being superior to placebo, an additional study found the treatment superior to 150mg sustained release tablets of bupropion, a norepinephrine and dopamine reuptake inhibitor (NDRI). 

Common adverse effects associated with Auvelity included dizziness, headache, diarrhea and dry mouth, among  others. 

“With symptom improvement happening at week one and then remission happening by week two, the combination of those two is incredibly differentiating in the marketplace right now,” said Lori Englebert, executive vice president of Axsome’s commercial and business development, in a statement. “We’re pretty excited about the product.” 

The company hopes to set the price for the treatment in the coming weeks.

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