Recurrent Serotonin Syndrome After Ketamine-assisted Electroconvulsive Therapy: A Case Report and Review of the Literature.

A 72-year-old woman developed serotonin syndrome on two separate occasions after receiving ketamine for electroconvulsive therapy. Serotonin syndrome involves changes in mental status, autonomic function, and neuromuscular control. Electroconvulsive therapy may increase serotonin transmission by transiently opening the blood-brain barrier, raising antidepressant levels in the brain, and by acting on 5-HT1A and 5-HT2A receptors. Ketamine can also boost serotonin release by increasing glutamate activity in the medial prefrontal cortex. A literature review found five prior cases of serotonin syndrome with electroconvulsive therapy and one with ketamine alone. This is the only reported case of recurrent serotonin syndrome from combining both treatments. There is no evidence that adding ketamine to electroconvulsive therapy improves efficacy, so caution is warranted.

Study at a glance

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.