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SUMMARY
- Routine measurement or monitoring of esketamine (ESK) plasma levels is not required.
- Therapeutic drug monitoring was not performed in the ESK clinical trial program in treatment-resistant depression as a means of assessing a relationship between plasma concentrations and therapeutic efficacy/tolerability.
- In phase 3 studies of SPRAVATO, efficacy was assessed based on the Montgomery-Åsberg Depression Rating Scale and tolerability was determined based on adverse event reporting and scales to assess specific safety concerns.1-7
- No accumulation of ESK in plasma was observed following twice-a-week administration.8
- Following nasal spray administration, the mean absolute bioavailability of ESK is 48%.9
- The time to reach maximum ESK plasma concentration is 20 to 40 minutes after the last nasal spray of a treatment session.8
- After maximum serum concentration (Cmax) was reached, the decline in plasma ESK concentrations was biphasic, with a rapid decline for the initial 2 to 4 hours and a mean terminal half-life that ranged from 7 to 12 hours.8
- Noresketamine, the major metabolite of ESK, had a rapid initial decline of 4 hours and a mean terminal half-life of approximately 8 hours.9
Literature Search
A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 06 December 2024.
| 1 | 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):19m13191. |
| 2 | Ionescu DF, Fu DJ, Qiu X, et al. Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive diorder who have active suicide ideation with intent: results of a phase 3, double-blind, randomized study (ASPIRE II). Int J Neuropsychopharmacol. 24(1):22-31. |
| 3 | 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. |
| 4 | 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. |
| 5 | Popova V, Daly EJ, Trivedi M, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidpressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019;176(6):428-438. |
| 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 | Daly EJ, Trivedi MH, Janik A, et al. 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. |
| 8 | Perez-Ruixo C, Rossenu S, Zannikos P, et al. Population pharmacokinetics of esketamine nasal spray and its metabolite noresketamine in healthy subjects and patients with treatment-resistant depression. Clin Pharmacokinet. 2021;60(4):501-516. |
| 9 | Center for Drug Evaluation and Research. Clinical Pharmacology and Biopharmaceutics Review. NDA 211243 - SPRAVATO (esketamine) - Reference ID: 4398871. 2019- [2024 December 06]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211243Orig1s000ClinPharmR.pdf |
