Ketamine nasal spray approved as a stand-alone treatment for difficult cases of depression

An emerging treatment for clinical depression has reached an important milestone. This week, the Food and Drug Administration approved Johnson & Johnson’s ketamine nasal spray, Spravato, as a stand-alone treatment for cases of depression that have not responded to other options.

J&J announced the additional FDA approval on Tuesday. Previously, Spravato was approved as an adjunctive treatment for treatment-resistant depression, in combination with an oral antidepressant. Expanded use portends a promising future for ketamine and similar drugs as a mental health intervention.

Spravato was first approved by the FDA in 2019, after years of research suggesting that ketamine treatment could offer unique, fast-acting antidepressant benefits. Although ketamine is perhaps best known as a recreational drug with dissociative effects, it has a long history of medical use as an anesthetic. Before Spravato’s approval, intravenous ketamine had become a growing, albeit off-label, option for difficult cases of depression. However, Spravato contains a different form of ketamine than the version used intravenously: a sibling chemical called esketamine.

In the years since their approval, Spravato and ketamine have continued to show their potential as treatments for depression. Studies following its publication have shown, for example, that ketamine may outperform other standard alternatives for treatment-resistant depression, such as certain antipsychotics. The FDA granted expanded approval of Spravato based on another post-marketing Phase 4 trial, comparing Spravato alone to a placebo.

The double-blind, randomized, controlled trial involved people with treatment-resistant depression, who were divided into three groups: two groups given different doses of Spravato twice a week for four weeks and a control group having received a placebo spray. According to the study, people taking Spravato experienced a significant and sustained reduction in depression symptoms compared to controls. For example, only 7.6% of patients taking a placebo experienced a clear remission of their symptoms, compared to 22.5% of people taking Spravato. The drug also seemed as safe as it appeared in earlier trials.

“Treatment-resistant depression can be very complicated, particularly for patients who do not respond to or cannot tolerate oral antidepressants,” said Bill Martin, global neuroscience therapeutic area leader in J&J’s Department of Innovative Medicine. , in a press release. “Spravato is now available as a stand-alone treatment, meaning patients can experience improvement in depressive symptoms as early as 24 hours and 28 days, without the need for daily oral antidepressants.”

Like any drug, ketamine is not without risks. When used for depression, common side effects may include sedation, dissociation, and respiratory depression (breathing that is too slow or shallow). These side effects and the potential risk of harmful dependence led the FDA to mandate a special treatment strategy for providing Spravato to patients, known as the Risk Evaluation and Mitigation Strategy, or REMS, program. People taking Spravato can only do so in clinics or doctor’s offices certified to distribute it, and only under direct medical supervision.

Nonetheless, Spravato’s expansion into a standalone therapy means that more people with treatment-resistant depression will be able to access the drug. In the long term, one of the main reasons researchers are so excited about ketamine is that the drug targets different receptors in the brain linked to depression compared to other medications. Not only does this allow ketamine to help people who have not responded to previous treatments, but it could one day mean the arrival of new drugs that work similarly. And if these drugs could be made even safer, then they could become first-line treatments for depression in general.