One of the last things to happen under commissioner Scott Gottlieb’s watch at the Food and Drug Administration (FDA) was the approval of Spravato, a nasal spray treatment of esketamine for use as an antidepressant in combination with an oral antidepressant.
Esketamine is a variation on ketamine—a non-opioid anesthetic used primarily by veterinarians but more commonly known as a street drug with psychedelic properties and severe effects called “K-holes.”
A clinical trial in 2006 showed promise for ketamine as a potential breakthrough for people suffering from severe depression that don’t respond to other drugs.
Psychiatrists had been prescribing it off-label for some time as the body of research on it grew, leading to the FDA’s Fast-Track, Breakthrough Therapy designations and recent FDA approval . It’s expected to cost between $4,720 and $6,785 a treatment and needs to be administered in a doctor’s office.
But while the hype for ketamine for treating depression has grown by leaps and bounds, different clinical trials have shown substantially difference success rates.
Every clinical trial tests different sets of patients with differing symptoms using different drug combinations.
But the discrepancy in the results can be large depending on who is overseeing the trial: Janssen Pharmaceuticals, the manufacturer of Spravato, or an independent researcher.
Of the 19 clinical trials for esketamine and depression registered on clinicaltrials.gov , all are overseen by Janssen Research & Development. And the vast majority of them list esketamine as providing a robust antidepressant effect.
Most list success rates for improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) above 90 percent, with little effect on placebo participants and few side effects. Effects are listed as rapidly onset and sustained.
Results for the trials are not posted on the clinicaltrials.gov site but in separately published academic papers.
While Janssen received the FDA approval for Spravato and funded all of the listed research on esketamine and depression, there is plenty of research on ketamine and depression with the results published on clinicaltrials.gov. And those results paint a very different picture.
One trial showed less than half of the participants going into remission with one suicide and another suffering from worsening depression.
Another showed ketamine performing near or worse than another antidepressant, diphenhydramine. Another showed ketamine performing similar to placebo, with 2 participants suffering from worsening depression. Another had some positive responses but that the effects weren’t sustained beyond a week.
In a National Institute of Medical Health study , researchers from Massachusetts General Hospital called ketamine unlikely to “become a practical treatment for most cases of depression” because it could potentially trigger adverse side effects and patients also typically relapse after treatment ends.
Some trials did show mixed results with potential for ketamine use as an antidepressant.
One showed a temporary improvement in the Beck Scale for Suicidal Ideation, although opioids showed an even better rate.
Eight out of 18 taking an intranasal version of ketamine , like that of Spravato, showed a marked improvement and that “these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression.”
But that study and a few others were headed by researchers from the Icahn School of Medicine at Mount Sinai. Janssen recently funded the Icahn school’s research into neuroscience and depression and at least two of the researchers on those studies received research support from Janssen.