In his presentation at the virtual meeting of the American Psychiatric Association in 2021, Dr. Richard C. Shelton, Professor Charles B. Ireland in the Department of Psychiatry and Behavioral Neurobiology at the University of Alabama at Birmingham and Director of the UAB Depression and Suicide Center discuss the functions and concerns of ketamine.
“This is not just a treatment or a treatment to be taken lightly,” Shelton said during part of his Q + A presentation. “On the other hand, we have seen remarkable results.”
Shelton began by discussing the functions of ketamine in the brain and how it restores regulatory processes for patients with mood disorders, using, for example, a study by Li et al.1
“Stressful experiences cause thorns and synapses to shrink or recede. The brain is less able to control or regulate the emotional state, “Shelton explained.
With the administration of ketamine there is an almost immediate increase in the formation of critical vertebrate and synaptic proteins.
“When you add ketamine to the system, you produce a rapid return and recovery of these spines and synapses. We see an effect within 24 hours, ”Shelton continued. “Ketamine has the ability to restore regulatory control of the brain and helps to theoretically normalize mood.”
Shelton shared data from 8 studies on ketamine and how it produces a rapid, strong effect for patients with severe, resistant mood disorders.2-9 and additional studies on how ketamine works in patients with suicidal ideation.10-13
“The good news: ketamine seems to really work in these patients with high treatment resistance,” Shelton said.
Shelton also addressed key concerns about ketamine, especially how challenging it can be to prescribe. First, the US Food and Drug Administration requires a “somewhat cumbersome” risk assessment program and mitigation strategy in which the clinic, provider, and patient must be enrolled in the program. There are preliminary obstacles to resolution, as well as problems with cost recovery. Nevertheless, Shelton finds more ketamine than he deserves.
“When I treated my first patient with IV ketamine in 2012, it was just amazing to see the effect appear within 24 hours,” Shelton said.
1. Li N, Liu RJ, Dwyer JM, et al. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by exposure to chronic stress. Psychiatry of Biol. 2011; 69 (8): 754-61.
2. Berman RM, Narasimhan M, Sanacora G, et al. A randomized clinical trial of repeated transcranial magnetic stimulation in the treatment of major depression. Psychiatry of Biol. 2000; 47 (4): 332-337.
3. Zarate CA, Singh JB, Carlson PJ, et al. A randomized study of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch General of Psychiatry. 2006; 63 (8): 856-864.
4. Singh JB, Fedgchin M, Daly EJ, et al. A double-blind, randomized, placebo-controlled, dose-dose study of intravenous ketamine in patients with treatment-resistant depression. Am J Psychiatry. 2016; 173 (8): 816-826.
5. Daly EJ, Singh JB. Additional intranasal esketamine in treatment-resistant depression-response. JAMA Psychiatry. 2018; 75 (6): 654-655.
6. Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of a fixed dose of esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results from a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019; 22 (10): 616-630.
7. Popova V, Daly EJ, Trivedi M, et al. Efficacy and safety of a flexible-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.
8. Daly EJ, Trivedi M, 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.
9. Weiss E, Aluisio L, Holder R, et al. Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: a long-term safety assessment in phase 3, open-label study (SUSTAIN-2). J Clin Psychiatry. 2020; 81 (3).
10. Wilkinson ST, Ballard ED, Bloch MH, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: Systematic review and meta-analysis of data for individual participants. Am J Psychiatry. 2018; 175 (2): 150-158.
11. Canuso CM, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal escetamine for the rapid reduction of symptoms of depression and suicide in patients at immediate risk of suicide: results from a double-blind, randomized, placebo-controlled study. Am J Psychiatry. 2018; 175 (7): 620-630.
12. Fu DJ, Ionescu DF, Li X, et al. Esketamine nasal spray to rapidly reduce the main symptoms of depressive disorder in patients who have an active suicidal ideation with intent: a double-blind, randomized study (ASPIRE I). J Clin Psychiatry. 2020; 81 (3).
13. 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 an active idea of suicide with intent: Results of a phase 3, double-blind, randomized study (ASPIRE II). Int J Neuropsychopharmacol. 2021; 24 (1): 22-31.