SAN DIEGO — Intranasal esketamine spray (Spravato) helped achieve a rapid reduction in depressive symptoms among people at imminent risk for suicide, according to the phase III ASPIRE-2 study.
When added to standard of care, recipients of esketamine spray saw a significant 3.9-point improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score relative to placebo within 24 hours after the first dosage (16 vs 12.2-point improvement in placebo), reported Dawn Ionescu, MD, of drug developer Janssen Research & Development in Titusville, New Jersey, at Psych Congress 2019.
This treatment benefit was even apparent within 4 hours of administration (12.5 vs 8.5-point improvement in placebo), which was a predefined secondary endpoint of the first of two phase III global studies looking at this therapy in people at imminent risk for suicide.
However, in a secondary endpoint, both esketamine and placebo improved severity of suicidality scores within 24 hours of initial dose, without any significant treatment difference between the two (-1.0 vs -1.0).
“This may be due to the substantial beneficial effects of inpatient psychiatric hospitalization in diffusing the acute suicidal crisis in patients in both treatment groups,” the researchers pointed out.
In another secondary endpoint, more patients on esketamine were able to achieve remission of depressive symptoms after 4 hours, 24 hours, and 25 days after the initial dose.
This therapy was FDA approved in March 2019 as adjunct to an oral antidepressant for treatment-resistant depression. Prior phase III studies have demonstrated its efficacy in those with moderate to severe treatment-resistant depression already on an antidepressant.
“This is the first global registration program of patients with active suicidal ideation and intent, a vulnerable and heretofore understudied population for whom there is great unmet medical need,” explained Ionescu’s group.
The study included 230 adults with major depressive disorder screening in the emergency department or another “permitted” setting, deeming them at imminent risk for suicide. Half of patients were randomized to receive 84 mg of esketamine nasal spray twice-weekly for 4 weeks, while the other half received placebo. The treatment was added to existing standard of care, which for these patients included an initial inpatient hospitalization, a newly initiated or optimized antidepressant, as well as intensive visits twice per week.
Adverse events seen with esketamine were consistent with previous findings, the most common of which were dizziness, dissociation, nausea, and dysgeusia. The drug already carries a boxed warning for risk of sedation and problems with attention, judgment, thinking, abuse, misuse, and suicidal thoughts and behaviors.
There were three suicide attempts reported in the esketamine, as well as the placebo groups, although no deaths occurred throughout the 90-day treatment and follow-up period.
Based upon the ASPIRE I & II trials, Janssen announced they submitted a New Drug Application to the FDA in October 2019, seeking a new indication for the rapid reduction of depressive symptoms in adults with major depression with active suicidal ideation with intent. If approved, this would be the first approved treatment for imminent suicide risk.
The studies were funded by Janssen. Co-authors are company employees.
Source: MedicalNewsToday.com
