A new study finds that a nasal spray formulated from the anesthetic ketamine is a safe, fast-acting and effective treatment for treatment-resistant depression. Researchers presented the findings this week at the annual meeting of the American Psychiatric Association.
Esketamine, the intranasal formulation of ketamine, recently received FDA approval as a depression treatment when used with an oral antidepressant, based in part on findings from this study. The results open the door to a potential new alternative for the estimated 30% of depression patients suffering from treatment-resistant depression.
The study included 197 adults from 39 outpatient centers over a two-year period. All of the participants had either moderate or severe depression and hadn’t responded well to at least two antidepressants in the past. Participants were randomly assigned to one of two groups: The first switched from their current antidepressant treatment to esketamine nasal spray and a new oral antidepressant; the other switched from their current treatment to a placebo nasal spray and a new antidepressant.
The results showed significant improvements in depression symptoms among those in the esketamine group compared to the placebo group four weeks into the study, with signs of improvement starting much earlier.
“The study supports the efficacy and safety of esketamine nasal spray as a rapidly acting antidepressant for patients with treatment-resistant depression,” the study concluded.
“Not only was adjunctive esketamine therapy effective, the improvement was evident within the first 24 hours,” said Michael Thase, M.D., one of the study authors. “The novel mechanism of action of esketamine, coupled with the rapidity of benefit, underpins just how important this development is for patients with difficult-to-treat depression.”
The researchers reported that most of the negative side-effects in the esketamine group, including dissociation, nausea, vertigo, dysgeusia (impaired sense of taste) and dizziness, disappeared within a couple of hours. A small percentage of patients dropped out of the study due to side effects.
Ketamine has been in headlines for more than a decade as the party drug (aka “Special K”) with promise of becoming a next-generation depression treatment. Early studies showed patients with a history of treatment-resistant depression responded well to ketamine almost immediately. Those studies generally used intravenous ketamine at a low enough dose to not deliver anesthetic effects (what ketamine was originally designed to do in humans and animals), but intravenous ketamine for the treatment of depression hasn’t been approved by the FDA. The intranasal formulation (brand name Spravato) received FDA approval in March of this year but is only available through a restricted distribution system with a certified clinic or doctor’s office.
The news isn’t entirely upbeat, however, with some researchers urging caution as the drug moves closer to pharmacy shelves. In commentary accompanying the study in the American Journal of Psychiatry, Alan Schatzberg, M.D., from Stanford University School of Medicine, cautioned that while this study shows potential benefits of using the drug, “there are more questions than answers…and care should be exercised in its application in clinical practice.”
Schatzberg pointed out that clinicians don’t have adequate information about how often the medication should be prescribed, how long patients should use it, or what the correct course of action should be if patients eventually stop responding to it.
He also highlighted the potential for abuse, echoing concerns raised by many health professionals all along the drug’s road to approval. Using the history of opioids as an example, he added, “We have witnessed four decades of supposedly new and safer opioids that have turned out often to be, if anything, even more abusable and lethal.”
“Still, the agent [esketamine] could be helpful to many patients with refractory depression,” Schatzberg said, ending on the positive, “and efforts to develop rapidly acting agents for severely depressed patients need to be applauded.”
The study was published online in the American Journal of Psychiatry.