Neuro endocrinology lettersJun 28, 2013

Link between ketamine’s antidepressant effects and psychosis-like side effects in unipolar depression

Psychedelic Science Weekly Brief ↗PubMed ↗

Updated Apr 3, 2026

Abstract

A single ketamine infusion (0.54 mg/kg) was shown to produce a superior antidepressant effect compared to placebo in a clinical trial with 27 patients.

Higher intensity of psychotomimetic symptoms during ketamine administration was associated with improved mood ratings in the following week, peaking on day seven.
Ketamine demonstrated significant antidepressant effects across all assessment days (day 1, 4, and 7) as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).
Effect sizes for ketamine's superiority over placebo were 0.62 on day 1, 0.57 on day 4, and 0.44 on day 7.
No significant correlation was found between ketamine or nor-ketamine plasma levels and changes in MADRS scores at any time point.
A substantial relationship between ketamine's antidepressant and psychotomimetic effects was observed, potentially linked through NMDA receptors.

Simplified

OBJECTIVES: Ketamine and other NMDA (N-methyl-D-aspartate) antagonists produce fast-acting antidepressant-like effects, although the underlying mechanism is unclear. Furthermore, high affinity NMDA antagonists such as ketamine are associated with psychotomimetic effects. To date the link between the antidepressant and psychotomimetic effects of ketamine has not been explored. We examined the relationship between the antidepressant and psychotomimetic effects of a single ketamine infusion in subjects diagnosed with major depressive disorder.

METHODS: In a double-blind, cross-over, placebo-controlled, two weeks clinical trial we studied the effects of ketamine (0.54 mg/kg within 30 min) in a group of 27 hospitalized depressive patients.

RESULTS: Higher intensity of psychotomimetic symptoms, measured using BPRS, during ketamine administration correlated with alleviation in mood ratings during the following week with maximum on day seven. Ketamine was superior to placebo in all visits (day 1, 4, and 7) assessed by MADRS with effect size (Cohen´s d) of 0.62, 0.57, and 0.44 respectively. There was no significant correlation between ketamine and nor-ketamine plasma levels and MADRS score change at any study time point.

CONCLUSION: The substantial relationship between ketamine's antidepressant and psychotomimetic effects was found. This relationship could be mediated by the initial steps of ketamine's action, trough NMDA receptors, shared by both ketamine's clinical effects.

Link between ketamine’s antidepressant effects and psychosis-like side effects in unipolar depression

Abstract

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief

Abstract

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief