Recurrent Serotonin Syndrome After Ketamine-assisted Electroconvulsive Therapy: A Case Report and Review of the Literature.
Aniruddha Deka, Emmanuel Joseph, Neha Sharma, Tirsit Berhanu, Jonathan Kaplan
Journal of Psychiatric Practice May 1, 2024 DOI: 10.1097/PRA.0000000000000787 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case report and literature review Peer reviewed |
|---|---|
| Sample size | 1 |
| Population | 72-year-old woman |
| Interventions | Ketamine Electroconvulsive therapy |
| Topics | Esketamine Ketamine Serotonin |
| Keywords | Depression treatment Drug interactions Serotonin syndrome Patient safety Psychiatric medicine |
| Citations | 3 |
| Key findings | Combining ketamine with electroconvulsive therapy can precipitate recurrent serotonin syndrome in patients taking serotonergic medications. |
Abstract
Serotonin (5-HT) syndrome (SS) consists of changes in mental status as well as autonomic and neuromuscular changes. Though not well understood, serotonergic pathways have been implicated in the mechanism of action of electroconvulsive therapy (ECT). Ketamine has been used as an induction agent in ECT and as therapy for treatment-resistant depression. Utilizing a case report and literature review, we explored the underlying serotonergic mechanisms of ECT and ketamine by which a syndrome of serotonin toxicity may be precipitated. We describe the case of a 72-year-old woman who developed recurrent SS on 2 occasions in similar circumstances involving the administration of ketamine for ECT. In our literature review, we found 5 cases in which SS was associated with ECT and 1 case linking ketamine to SS. There is emerging evidence that the mechanism of ECT involves 5-HT1A and 5-HT2A receptors, the same receptors that are involved in SS. ECT can transiently increase the permeability of the blood-brain barrier, leading to increased levels of antidepressants in the brain. ECT can, therefore, enhance 5-HT transmission and the likelihood of SS in the presence of serotonergic agents. The effect of ketamine on 5-HT transmission is mediated by the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Ketamine increases α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid activity in the medial prefrontal cortex, which leads to downstream 5-HT release through glutamate. Through this mechanism, ketamine can increase 5-HT transmission, leading to SS. To our knowledge, this is the only case report of recurrent SS with concurrent use of ECT and ketamine. As ketamine is frequently used in ECT and many patients undergoing ECT are on serotonergic medications, it is important to recognize ketamine as a potential risk factor for SS. There is no evidence for added efficacy when combining ECT and ketamine. Thus, one should proceed with caution when combining these treatments. The burgeoning use of ketamine in ambulatory settings makes it necessary to elucidate the risks, which we discuss further. More research is needed into the mechanisms of ketamine and ECT, specifically how the combination of these treatments influence 5-HT levels.
Comparable studies
Other case reports and case series on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Lasting Neuropsychiatric Sequelae of (??)Methylenedioxymethamphetamine (???Ecstasy???) in Recreational Users Persons who ingested large doses of MDMA | 1991 | Case study | n = 2 |
| Striatal serotonin is depleted in brain of a human MDMA (Ecstasy) user Chronic MDMA user | 2000 | Case study | n = 1 |
| Death following ingestion of MDMA (ecstasy) and moclobemide People who died after ingesting moclobemide and MDMA | 2003 | Case series | n = 4 |
| Ecstasy Intoxication: An Overlap Between Serotonin Syndrome and Neuroleptic Malignant Syndrome A 19-year-old woman and 15 other cases reported in the literature | 1996 | Case report and literature review | n = 16 |
| Recurrent seizures and serotonin syndrome following "2C-I" ingestion. 19-year-old male who insufflated 2C-I | 2013 | Case report | n = 1 |
Citations in the library
Cites 12
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- 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 April 16, 2018
- Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry 2018
- Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial American Journal of Psychiatry December 5, 2017
and 7 more in the library