By Ed Cara Published January 22, 2025 | Comments (1) | Ketamine has become an important alternative for treatment-resistant depression in recent years, Shablon via Shutterstock An emerging treatment for clinical depression has reached an important milestone. This week, the Food and Drug Administration approved Johnson & Johnsons ketamine-based nasal spray, Spravato, as a standalone therapy for cases of depression that havent responded to other options. J&J announced the FDAs supplemental approval Tuesday. Previously, Spravato was approved as an add-on therapy for treatment-resistant depression, in conjunction with an oral antidepressant. The expanded use signals a promising future for ketamine and similar drugs as a mental health intervention. Spravato was first approved by the FDA in 2019, following years of research suggesting that ketamine therapy could provide unique and fast-acting antidepressant benefits. Though ketamine is perhaps more infamously known as a recreational drug with dissociative effects, its long used medically as an anesthetic. Prior to Spravatos approval, intravenous ketamine had became 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 intravenouslya chemical sibling called esketamine. In the years since its approval, Spravato and ketamine have continued to show their potential as a depression treatment. Studies following its release have found, for instance, that ketamine can outperform other standard alternatives for treatment-resistant depression, such as certain antipsychotics. The FDA granted Spravatos expanded approval on the basis of another post-market phase 4 trial, one that compared Spravato alone to a placebo. The double-blinded, randomized, and controlled trial involved people with treatment-resistant depression, who were assigned to three groups: two groups who received different doses of Spravato twice a week for four weeks and a control group who 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 instance, compared to 22.5% of people taking Spravato. The drug also appeared to be as safe as its appeared in earlier trials.Treatment-resistant depression can be very complicated, especially for patients who do not respond to oral antidepressants or cannot tolerate them, said Bill Martin, the global therapeutic area head of neuroscience at J&Js innovative medicine department, in a statement. Spravato is now available as a standalone treatment, meaning patients may experience improvements in depressive symptoms as early as 24 hours and at 28 dayswithout the need for daily oral antidepressants. Like any drug, ketamine isnt without its risks. When used for depression, common side effects can include sedation, dissociation, and respiratory depression (overly slow or shallow breathing). These side effects and the potential risk of harmful dependence have led to the FDA mandating a special treatment strategy for providing Spravato to patients, known as a Risk Evaluation and Mitigation Strategy, or REMS, program. People taking Spravato can only do so at clinics or medical offices certified to distribute it, and only under direct medical supervision.Still, Spravatos 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 big reason why researchers have been so excited about ketamine is that the drug targets different receptors in the brain tied to depression than other medications. This not only allows ketamine to possibly help people who havent responded to past treatments, it could someday mean the arrival of newer drugs that work in a similar way. And if these drugs can be made even safer, then they could also become frontline treatments for depression in general.Daily Newsletter