Midazolam attenuates ketamine-induced abnormal perception and thought process but not mood changes

Area of Science:

• Anesthesiology and Pharmacology
• Neuroscience
• Psychopharmacology

Background:

• Ketamine is an anesthetic known to induce significant alterations in perception, mood, and cognition.
• Understanding the potential interactions and modulatory effects of co-administered drugs is crucial for clinical safety and efficacy.
• Midazolam is a benzodiazepine commonly used for sedation and anxiolysis.

Purpose of the Study:

• To investigate the effects of midazolam at a plasma concentration of 30 ng/mL on ketamine-induced changes in perception, mood, and cognition.
• To assess the safety and efficacy of combining midazolam with ketamine in a controlled volunteer study.

Main Methods:

• Eleven healthy volunteers received ketamine to achieve target plasma concentrations of 50, 100, or 150 ng/mL.
• Perception, mood, and thought processes were evaluated using visual analog scales.
• Cognition was assessed using the Mini-Mental State Examination (MMSE), with midazolam administered to maintain a steady plasma concentration.

Main Results:

• Ketamine significantly altered perceptions of body, surroundings, time, reality, sounds, and meaning.
• Both ketamine and midazolam, individually and in combination, reduced energy and clearheadedness and impaired thought processes.
• Co-administration of midazolam reduced the incidence of ketamine-induced perceptual and thought process abnormalities, without affecting mood or recall.

Conclusions:

• Midazolam effectively attenuates ketamine-induced alterations in perception and thought processes.
• The findings suggest a potential role for midazolam in mitigating some of the psychotomimetic and cognitive side effects of ketamine.
• Further research is warranted to explore optimal dosing and clinical applications of this combination.