(1342) Serotonin Syndrome due to Kratom and Antidepressant Interaction: A Case Study

Introduction: Serotonin syndrome caused by the stimulation of the postsynaptic 5-HT1A and 5-HT2A receptors by serotonergic drugs can lead to severe hyperthermia, agitation, autonomic instability, and even death. We report a case of serotonin syndrome in a 28-year-old male after smoking kratom concomitantly with sertraline and bupropion.

Description: A patient presented at Yale New Haven Hospital after consistently vomiting, experiencing a severe headache, and seizing at home. During admission, he had clonus seizures and extreme agitation. Droperidol and midazolam were given for agitation without effect and further agitation required initiation of propofol and ketamine while intubated. Head CT did not reveal any acute intracranial abnormalities. Due to worsening clonus, cyproheptadine was started for management of serotonin syndrome. This diagnosis was confirmed by the Hunter Criteria, which was positive for an inducible clonus with agitation and tremor with hyperreflexia, while on a serotonergic agent. Also confirming the diagnosis, the patient’s agitation and clonus improved with cyproheptadine. After seven days, the patient’s agitation resolved, and he returned to his baseline. Bupropion was discontinued given concern for reduction of seizure threshold. The patient was not interested in continuing sertraline and instead opted to follow up frequently with the behavioral health clinic. He was counseled on the negative consequences of illicit drug use and the adverse events associated with herbal supplements.

Discussion: There have been case reports of serotonin syndrome occurring when kratom is used in combination with serotonergic drugs such as sertraline. However, there is not enough data to confirm widespread interactions between these drugs. Kratom's psychoactive effects are caused by its interaction with the mu-opioid receptors. Kratom may bind to serotonin receptors and inhibit CYP2D6 and CYP3A4, which could increase exposure to medications like sertraline that use these pathways. Bupropion is also a strong CYP2D6 inhibitor and can further potentiate an increase in serotonin. This case highlights the importance of understanding the mechanisms of action of all drugs, including herbal supplements and considering how these mechanisms can interact and cause harmful effects.