Ketamine Nasal Spray Approved as Standalone Treatment for Severe 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-based nasal spray, Spravato, as a stand-alone therapy for depression cases that have not responded to other options.

J&J announced additional FDA approval on Tuesday. Previously, Spravato was approved as an add-on therapy for treatment-resistant depression, in conjunction with an oral antidepressant. Expanded use signals a promising future for ketamine and similar drugs as mental health interventions.

You were fine first approved by the FDA in 2019, after years of research suggesting that ketamine therapy could provide unique and rapid antidepressant benefits. Although ketamine is perhaps most infamously known as a recreational drug with dissociative effects, it has long been used medically as an anesthetic. Before Spravato’s approval, intravenous ketamine had become a growing, if off-label, option for difficult cases of depression. However, Spravato contains a different form of ketamine than the version that is used intravenously – a chemical sibling called esketamine.

In the years since its approval, Spravato and ketamine have continued to show their potential as a treatment for depression. Studies after its release have found, for example, that ketamine can overcome other standard alternatives for treatment-resistant depression, such as some antipsychotics. The FDA granted Spravato’s expanded approval based on another post-marketing Phase 4 trial, which compared Spravato alone to a placebo.

The double, randomized and controlled trial involved people with treatment-resistant depression, who were assigned to three groups: two groups that received different doses of Spravato twice a week for four weeks and a control group that had received a placebo spray. Those on Spravato experienced a significant and sustained reduction in depression symptoms compared to controls, the study found. Only 7.6% of patients taking a placebo experienced a clear remission of their symptoms, for example, compared to 22.5% of people taking Spravato. The drug also appeared to be safe as it appeared in previous trials.

“Treatment-resistant depression can be very complicated, especially for patients who do not respond to or cannot tolerate oral antidepressants,” said Bill Martin, the head of the global therapeutic area of ​​neuroscience in the department of J&J’s innovative medicine, in a declaration. “Spravato is now available as a stand-alone treatment, which means patients can experience improvement in depressive symptoms within 24 hours and up to 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 (too slow or shallow breathing). These side effects and the potential risk of harmful addiction have led the FDA to mandate a special treatment strategy for providing Spravato to patients, known as a Risk Evaluation and Mitigation Strategy, or REMS, program. People who take Spravato can only do so in clinics or medical offices certified for distribution, and only under direct medical supervision.

However, expanding Spravato into a standalone therapy means more people with treatment-resistant depression will be able to access the drug. In the long run, a big reason why researchers have been so excited about ketamine is that the drug targets different receptors in the brain linked to depression than other medications. This not only allows ketamine to help people who have not responded to past treatments, it could mean one day the arrival of newer drugs which works in a similar way. And if these drugs can be made even safer, then they could also become first-line treatments for depression in general.