Janssen Pharmaceutical Companies, a subsidiary of Johnson & Johnson (JNJ.NYSE) have submitted a supplemental New Drug Application to the U.S. Food and Drug Administration (FDA) for an esketamine nasal spray.
SPRAVATO is an esketamine treatment for the “rapid reduction of depressive symptoms in adult patients with major depressive disorder (MDD) who have active suicidal ideation with intent.”
Janssen’s submission to the FDA comes off the heels of Phase 3 clinical studies to evaluate the efficacy and safety of esketamine in patients with MDD, a group “typically excluded from antidepressant treatment studies,” according to Johnson & Johnson.
Anti-depressant medications have been the go-to for years, but they take time to become effective, and there is a risk of increased suicidality among patients prescribed anti-depressants.
Patients experiencing suicidal ideation may benefit from the use of acute, near-instantaneous treatment, and “Although currently available antidepressants are effective for many patients, their onset of effect can take four to six weeks, offering limited benefit to those in urgent need,” according to Dr. Carla Canuso, M.D., senior director of clinical research with Janssen.
“In the ASPIRE I & II trials, 54 percent and 47 percent, respectively, of the SPRAVATOTM plus SOC group achieved remission (MADRS score ≤ 12) by the end of the double-blind period,” according to the study.
Janssen says the clinical improvements in patients during the double-blind period was maintained over the nine-week follow-up period in conjunction with the use of oral antidepressants.
The most common side effects of SPRAVATO were dizziness, dissociation, nausea, somnolence, blurred vision, vomiting, paresthesia, increased blood pressure and sedation.
Esketamine leaves more questions
Esketamine differs from ketamine in that it seems to cause fewer side-effects such as hallucinations and derealisation.
But the effectiveness of esketamine as a long-lasting treatment is still unknown. In a 2018 study led by Canuso, suicidal thoughts decreased between the baseline to the four hour mark in patients who used esketamine, but similar improvements were not observed at 24 hours post-treatment, nor on day 25 of observation which was the double-blind endpoint.
Improvements in depressive symptoms were “numerically greater in the esketamine group compared with the placebo group at all time points over the 4-week double-blind phase,” however.
But a 2019 study found esketamine combined with antidepressant medications showed significant improvements over the group which was given antidepressants and a placebo.
In an interview with Vice News, Charles Nemeroff, a University of Miami psychiatrist, said he was concerned about the use of ketamine due to the potential for abuse and a lack of long-term data on ketamine or esketamine users.
“…many patients who receive ketamine have not yet received other FDA-approved treatments for depression such as repetitive transcranial magnetic stimulation or a variety of medication combinations, not to mention evidence-based psychotherapy such as [cognitive behavioral therapy].”
Dr. Alan F. Schatzberg wrote an editorial article in May as a word of caution to counter the excitement surrounding esketamine as a treatment.
In it, he said the 2019 study on esketamine’s efficacy was “in the mild range,” and that readers “should have cause to wonder, with a small effect and a rather limited control comparison, whether efficacy has been truly demonstrated.”
Schatzberg also raised concerns as to the three suicides which occurred four to 20 days after the last dose of esketamine, none of which, he says, were from the placebo group:
“Two of the patients who died by suicide showed no previous signs of suicidal activity during the study, either at baseline or at the last visit. This suggests a protracted withdrawal reaction, as has been reported with opioids, and one that is different from the more physical withdrawal symptoms seen acutely with opioids.”