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SUMMARY
- Dosing:
- Treatment-Resistant Depression (TRD) Studies – The recommended dose of SPRAVATO during the first 4 weeks is 56 mg or 84 mg twice per week in adults. Dosage adjustments should be made based on efficacy and tolerability.1
- ASPIRE-I and ASPIRE-II Studies – SPRAVATO was studied at 84 mg twice weekly for 4 weeks.2,3 After Day 1, a single dose reduction to 56 mg was permitted for intolerance and continued thereafter.
- Although consecutive day administration of SPRAVATO during induction was not studied, and investigators were advised not to dose on consecutive days, the pharmacokinetics of SPRAVATO does not suggest significant concerns with such approach when necessary.
CLINICAL DATA
Induction Schedule in Phase 3 Studies
In patients with TRD, during the 4-week induction period of SPRAVATO phase 3 studies, SPRAVATO was dosed twice weekly.4-8 Dosing on consecutive days was not studied during the SPRAVATO phase 3 studies and investigators were advised not to dose on consecutive days.9 However, the time to reach maximum ESK plasma concentration is 20 to 40 minutes after the last nasal spray of a treatment session and the mean terminal half-life (t1/2) of ESK is relatively short (7 to 12 hours), therefore although not optimal, the pharmacokinetic profile of the product suggests that there are no significant concerns with consecutive day dosing, if needed.
Literature Search
A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT Drug databases (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 25 August 2026.
| 1 | Center for Drug Evaluation and Research. Clinical Pharmacology and Biopharmaceutics Review. NDA 211243 - SPRAVATO (esketamine) - Reference ID: 4397019. 2019- [cited 2024 May 14]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211243Orig1s000ClinPharmR.pdf |
| 2 | Fu DJ, Ionescu DF, Li X, et al. Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent: Double-Blind, Randomized Study (ASPIRE I). J Clin Psychiatry. 2020;81(3). |
| 3 | Ionescu DF, Fu DJ, Qiu X, et al. Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II). Int J Neuropsychopharmacol. 2020;24(1):22-31. |
| 4 | Popova V, Daly EJ, Trivedi M, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019;176(6):428-438. |
| 5 | Daly EJ, Trivedi MH, Janik A, et al. Supplement to: Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2019;76(9):893-903. |
| 6 | Ochs-Ross R, Daly EJ, Zhang Y, et al. Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression-TRANSFORM-3. Am J Geriatr Psychiatry. 2020;28(2):121-141. |
| 7 | Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616-630. |
| 8 | Wajs E, Aluisio L, Holder R, et al. Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: assessment of long-term safety in a phase 3, open-label study (SUSTAIN-2). J Clin Psychiatry. 2020;81(3):19m12891. |
| 9 | Daly EJ, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2018;75(2):139-148. |
