Ketamine Enhances Visual Sensory Evoked Potential Long-term Potentiation in Patients With Major Depressive Disorder.
Rachael L Sumner, Rebecca McMillan, Meg J Spriggs, Doug Campbell, Gemma Malpas, Elizabeth Maxwell, Carolyn Deng, John Hay, Rhys Ponton, Ian J Kirk, Frederick Sundram, Suresh D Muthukumaraswamy
Biological psychiatry. Cognitive neuroscience and neuroimaging January 2020 DOI: 10.1016/j.bpsc.2019.07.002 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, active placebo-controlled crossover trial Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Patients with depression |
| Interventions | Ketamine Remifentanil |
| Dose | 0.44 mg/kg intravenous ketamine; 1.7 ng/mL remifentanil |
| Duration | Approximately 3 to 4 hours after dosing; clinical response assessed within 1 day |
| Measures | Montgomery-Åsberg Depression Rating Scale, visually evoked potentials, dynamic causal modeling |
| Topics | Depression Ketamine Esketamine |
| Keywords | Dynamic causal modeling Electroencephelography Ltp Visually evoked potentials |
| Key findings | Ketamine produced rapid antidepressant effects, with 70% of participants showing at least 50% reduction in depression symptoms within one day. Visual long-term potentiation was demonstrated in N1 and P2 evoked components, and ketamine enhanced P2 potentiation relative to placebo, which the authors interpret as evidence that LTP-based neural plasticity contributes to ketamine's antidepressant properties. |
Abstract
The rapid-acting clinical effects of ketamine as a novel treatment for depression along with its complex pharmacology have made it a growing research area. One of the key mechanistic hypotheses for how ketamine works to alleviate depression is by enhancing long-term potentiation (LTP)-mediated neural plasticity. The objective of this study was to investigate the plasticity hypothesis in 30 patients with depression noninvasively using visual LTP as an index of neural plasticity. In a double-blind, active placebo-controlled crossover trial, electroencephalography-based LTP was recorded approximately 3 to 4 hours following a single 0.44-mg/kg intravenous dose of ketamine or active placebo (1.7 ng/mL remifentanil) in 30 patients. Montgomery-Åsberg Depression Rating Scale scores were used to measure clinical symptoms. Visual LTP was measured as a change in the visually evoked potential following high-frequency visual stimulation. Dynamic causal modeling investigated the underlying neural architecture of visual LTP and the contribution of ketamine. Montgomery-Åsberg Depression Rating Scale scores revealed that 70% of participants experienced 50% or greater reduction in their depression symptoms within 1 day of receiving ketamine. LTP was demonstrated in the N1 (p = .00002) and P2 (p = 2.31 × 10-11) visually evoked components. Ketamine specifically enhanced P2 potentiation compared with placebo (p = .017). Dynamic causal modeling replicated the recruitment of forward and intrinsic connections for visual LTP and showed complementary effects of ketamine indicative of downstream and proplasticity modulation. This study provides evidence that LTP-based neural plasticity increases within the time frame of the antidepressant effects of ketamine in humans and supports the hypothesis that changes to neural plasticity may be key to the antidepressant properties of ketamine.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |