Which statement about ketamine at sub-hypnotic doses is true?

Which statement about ketamine at sub-hypnotic doses is true?

• A. Worsens depression
• B. Has no mood effects
• C. May treat severe depression at sub-hypnotic doses
• D. Causes only sedation

Answer: (C)

Ketamine at sub-hypnotic, or subanesthetic, doses can act as a rapid-acting antidepressant. At around 0.5 mg/kg given IV, many patients with severe depression, including treatment-resistant cases, experience mood improvement within hours, which is much faster than traditional antidepressants that take weeks. This antidepressant effect is the primary reason this dosing range is highlighted, and it isn’t just about sedation—the dose is low enough that the goal isn’t hypnosis, but rather a quick mood-enhancing outcome. The mood benefits are thought to arise from NMDA receptor antagonism leading to a cascade that increases AMPA throughput and promotes BDNF release and mTOR signaling, producing rapid synaptic changes in brain circuits involved in mood and cognition. While the effect can be transient and may require repeated dosing for lasting benefit, sub-hypnotic ketamine is known for this rapid antidepressant action rather than simply causing sedation or having no mood effect.

Ketamine at sub-hypnotic, or subanesthetic, doses can act as a rapid-acting antidepressant. At around 0.5 mg/kg given IV, many patients with severe depression, including treatment-resistant cases, experience mood improvement within hours, which is much faster than traditional antidepressants that take weeks. This antidepressant effect is the primary reason this dosing range is highlighted, and it isn’t just about sedation—the dose is low enough that the goal isn’t hypnosis, but rather a quick mood-enhancing outcome. The mood benefits are thought to arise from NMDA receptor antagonism leading to a cascade that increases AMPA throughput and promotes BDNF release and mTOR signaling, producing rapid synaptic changes in brain circuits involved in mood and cognition. While the effect can be transient and may require repeated dosing for lasting benefit, sub-hypnotic ketamine is known for this rapid antidepressant action rather than simply causing sedation or having no mood effect.