Ketamine for acute catatonia: A case report

Research into the anesthetic ketamine is gradually expanding, and the use of this agent for treating various psychiatric illnesses, including both unipolar and bipolar depression, has been increasing.² Empiric evidence suggests ketamine is effective for certain psychiatric disorders, but the mechanism of action remains unclear. Although the evidence base is small, additional cases demonstrating the effectiveness of ketamine in the treatment of acute catatonia might make it a therapeutic option for use by psychiatrists and emergency medicine clinicians.

In this article, we discuss ketamine’s possible role in the treatment of catatonia, possible adverse effects, dosing strategies, and theories about ketamine’s mechanism of action.

Ketamine’s utility in psychiatry

Ketamine is a rapid-acting anesthetic that acts primarily by antagonizing N-methyl-d-aspartate (NMDA) receptors in the CNS. It is characterized by dissociative anesthesia as it disrupts association pathways in the brain.³ Ketamine has been shown to be efficacious in treating MDD and posttraumatic stress disorder, and for the long-term management of chronic pain disorders, including fibromyalgia and many neuro­pathic conditions.^4-7 Esketamine is an intranasal formulation of ketamine that is FDA-approved for treatment-resistant depression.⁸ There is scant literature describing using ketamine for treating catatonia.

Previously, ketamine had been thought to induce a catatonic state, which was supported by a neurophysiologic model of catatonia that suggested the condition was caused in part by glutamate hypo­activity at the NMDA receptor.⁹ However, recent studies have shown that the NMDA receptor antagonists amantadine and memantine may be useful for treatment-refractory cases of catatonia, which suggests that a broader model of glutamatergic dysfunction, and not simply glutamate hypoactivity, may be more accurate.^10,11 Denysenko et al¹² proposed that the efficacy of memantine for patients with lorazepam-resistant catatonia could be explained by increases in dopamine levels in the frontal cortex and striatum. While this effect could explain why amantadine has anticatatonic effects, it does not explain why other NMDA antagonists such as ketamine are potentially pro-catatonic. Other proposed physiologic mechanisms explaining this difference include the fact that memantine and ketamine have differing effects on brain-derived neurotrophic factor (BDNF) expression and certain glutamatergic postsynaptic density proteins.^13,14

Ketamine originally was used for sedation, and much of its safety and risk profile has been developed from decades of administration as an anesthetic. Studies have found that ketamine has a large therapeutic window in children and adults.^15,16 Moreover, it does not depress the respiratory system. As an anesthetic, ketamine has a rapid onset and a quick resolution, with its sedative and disorienting effects resolving within 30 to 120 minutes.¹⁷ Ketamine’s rapid onset of action extends beyond its sedating effects. Trials with the intranasal spray esketamine for treatment-resistant depression have demonstrated an onset antidepressant effects within 2 days.¹⁸ This is much faster than that of traditional antidepressants, such as selective serotonin reuptake inhibitors.¹⁸ Based on these features, ketamine has the potential to be a useful medication in the emergency psychiatric setting, particularly for acute presentations such as catatonia.

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