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Cognitive outcomes from the randomised, active-controlled Ketamine for Adult Depression Study (KADS).

Donel M Martin¹, Anna J Harvey², Bernard Baune³

¹University of New South Wales, Sydney, NSW, Australia; Black Dog Institute, Sydney, NSW, Australia; The George Institute for Global Health, Sydney, NSW, Australia.

Journal of Affective Disorders

|February 20, 2024

Summary

This study found that repeated ketamine treatment, even at escalating doses, did not negatively impact cognition in adults with treatment-resistant depression over four weeks.

Keywords:

Cognition Ketamine TRD Treatment resistant depression

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Area of Science:

Neuroscience
Psychiatry
Clinical Trials

Background:

Ketamine shows rapid antidepressant effects for treatment-resistant depression.
Cognitive effects of repeated or higher-dose ketamine require further investigation.
The Ketamine for Adult Depression Study (KADS) aimed to clarify ketamine's cognitive profile.

Purpose of the Study:

To assess cognitive changes following repeated ketamine treatment versus midazolam.
To evaluate cognitive safety in two distinct dosing protocols (fixed and escalating).
To provide data on ketamine's cognitive impact in treatment-resistant Major Depressive Disorder (MDD).

Main Methods:

A multicentre, randomised, double-blind, active-controlled, parallel-group phase 3 trial.
Two cohorts investigated fixed (0.5 mg/kg) and escalating (0.5-0.9 mg/kg) ketamine doses over 4 weeks.
Cognitive measurements were taken at baseline and end of treatment.

Main Results:

No significant cognitive differences were observed between ketamine and midazolam in Cohort 1 (fixed dose).
Similarly, no cognitive differences were found between ketamine and midazolam in Cohort 2 (escalating dose).

Conclusions:

Repeated ketamine administration, at both fixed and escalating doses, appears cognitively safe in the short term.
Findings support the use of ketamine for treatment-resistant depression without significant cognitive impairment.
Further long-term studies may be warranted to fully understand cognitive effects.