Intranasal Esketamine – Psychopharmacology, Side effects and Clinical Application
Antidepressants such as SSRIs and SNRIs can be limited by their 3-6 weeks delay before a therapeutic effect is observed that can result in the need for multiple medication trials.
Treatment resistant depression (TRD) is defined as the failure of at least two trials and is characterised by severe morbidity in addition to higher rates of hospitalisation, suicidal ideation, and serious medical complications.
We had previously covered ketamine and esketamine.
In 2020, the FDA approved Esketamine nasal spray to treat depressive symptoms in adults with major depressive disorder (MDD) and acute suicidal ideation or behaviour.
The Australian TGA approved intranasal Esketamine (SPRAVATO) for TRD in 2021. According to the TGA:
Spravato is indicated for treatment resistant depression (Major Depressive Disorder in adults who have not responded adequately to at least two different antidepressants of adequate dose and duration to treat the current moderate to severe depressive episode).
Spravato is to be initiated in conjunction with a newly initiated oral antidepressant.
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Fedgchin, M., Trivedi, M., Daly, E. J., Melkote, R., Lane, R., Lim, P., … & Ravindran, A. (2019). 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). International Journal of Neuropsychopharmacology, 22(10), 616-630.
Wajs, E., Aluisio, L., Holder, R., Daly, E. J., Lane, R., Lim, P., … & Kasper, S. (2020). 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). The Journal of clinical psychiatry, 81(3).
Canuso, C. M., Singh, J. B., Fedgchin, M., Alphs, L., Lane, R., Lim, P., … & Drevets, W. C. (2018). Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. American Journal of Psychiatry, 175(7), 620-630.
Ionescu DF, Fu DJ, Qiu X, Lane R, Lim P, Kasper S, Hough D, Drevets WC, Manji H, Canuso CM. 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. 2021 Jan 20;24(1):22-31.