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The FDA has expanded the approval of Spravato (esketamine) nasal spray to include use as monotherapy for treatment-resistant depression (TRD), based on results from a phase 4 trial. The study demonstrated significant improvement in depressive symptoms within 24 hours of initial treatment, with sustained benefits through 4 weeks when compared to placebo. This new indication adds to Spravato’s existing approvals for TRD in combination with oral antidepressants and for major depressive disorder with acute suicidal ideation.
Key Points:
- The phase 4 TRD4005 trial evaluated Spravato monotherapy at 56mg and 84mg doses administered twice weekly, showing statistically significant improvements in MADRS scores compared to placebo (LS mean differences: -5.1 [95% CI, -7.9, -2.3] for 56mg; -6.8 [95% CI, -9.5, -4.1] for 84mg; P<.001)
- Clinical benefits emerged within 24 hours of initial administration and persisted through the 4-week treatment period, offering a rapid-acting option for TRD patients
- Common adverse reactions include dissociation, nausea, dizziness, headache, anxiety, vomiting, feeling drunk, increased blood pressure, and sedation
- Each Spravato device delivers two sprays totaling 28mg of esketamine and requires administration under direct healthcare provider supervision due to its Schedule III classification
- The Spravato REMS program mandates supervised administration and post-treatment monitoring to manage risks of sedation, dissociation, and respiratory depression
Treatment-resistant depression affects about 30% of people diagnosed with major depressive disorder.
Depression Summaries