There is sparse literature describing serotonin syndrome related to ketamine use. Ketamine has been shown to increase levels of glutamate in the medial prefrontal cortex. Higher levels of glutamine in turn stimulate excitatory glutamatergic neurons that project to the dorsal raphe nucleus. When stimulated, the dorsal raphe nucleus releases serotonin.6 There is also evidence that ketamine inhibits uptake of serotonin in synapses.7 These mechanisms combine to create a net increase in CNS-wide serotonin.
Ketamine is being increasingly used to treat depression and other conditions. This case report underscores the importance of considering serotonin syndrome when treating patients receiving ketamine, especially when it is used in conjunction with selective serotonin reuptake inhibitors.