Breaking Sad: Unleashing the Breakthrough Potential of Ketamine's Rapid Antidepressant Effects.
Drug Development Research December 2016 DOI: 10.1002/ddr.21347 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Sample size | 8 |
| Population | Depressed patients who had failed conventional medications |
| Intervention | Ketamine |
| Dose | low dose, subanesthetic doses |
| Topics | Ketamine Esketamine |
| Keywords | Ampa Nmda Antidepressant Psychedelic Treatment resistant depression |
| Key findings | Low-dose infused ketamine can induce remission of depression within 24 hours in patients who have failed conventional medications, distinguishing it from other antidepressants by rapid onset. However, benefits from a single subanesthetic infusion typically last less than three weeks, and infusions cause a transient psychedelic experience and blood pressure increases requiring monitoring, with a theoretical addiction risk. The author argues these limitations must be separated from ketamine's therapeutic effects to realize its potential. |
Abstract
Preclinical Research The surprising results of a small clinical trial on the effects of low dose ketamine, a 65-year old anesthetic drug that is also used off-label for chronic pain and recreationally as a club drug, in eight depressed subjects unleashed the most significant advance in antidepressant drug development in decades. That study and subsequent ones have demonstrated that low dose, infused ketamine is able to induce a remission of depression in patients who have failed conventional medications, within 24 h. The apparent increased efficacy and rapid onset of effect of ketamine distinguish it from all other current antidepressant treatments. However, a single infusion of subanesthetic doses of ketamine produces benefits that typically last <3 weeks. The infusions are associated with a transient "psychedelic" experience and increased blood pressure that requires monitoring. There is also a theoretical potential to induce ketamine addiction. These features limit ketamine's ability to be a widely used treatment for depression and thus limit is ability to have a meaningful impact on the heavy morbidity and mortality associated with this disorder, despite its "breakthrough" rate of efficacy and speed of action. While growing numbers of clinicians are using ketamine to treat treatment resistant depression, many in the depression field believe that the aforementioned limiting aspects need to be separated from its remarkable therapeutic effects in order to unlock the breakthrough potential of this agent. To that end, drug development efforts have focused on various features of ketamine as targets for optimization including its modulation of the NMDA receptor, its pharmacokinetics, its chirality and its active metabolites including HNK (2R, 6R)-hyroxynorketamine. Drug Dev Res 77 : 489-494, 2016. © 2016 Wiley Periodicals, Inc.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cited by 2
- Assessing the effects of methodological differences on outcomes in the use of psychedelics in the treatment of anxiety and depressive disorders: A systematic review and meta-analysis Journal of Psychopharmacology September 14, 2021
- The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease Neurology International June 23, 2022
Cites 7
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
and 2 more in the library