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The effects of ketamine on typical and atypical depressive symptoms

Lawrence T. Park, David A. Luckenbaugh, Steven Pennybaker, Matthew Hopkins, Ioline D. Henter, Marc S. Lener, Bashkim Kadriu, Elizabeth D. Ballard, Carlos A. Zarate

Acta Psychiatrica Scandinavica July 17, 2020 DOI: 10.1111/acps.13216 (opens in new tab) via OpenAlex

Summary

AI-generated from the abstract

A single intravenous dose of ketamine improved both typical/melancholic and atypical depressive symptoms in people with treatment-resistant major depressive disorder or bipolar depression. At one day after infusion, the effect was larger for typical/melancholic symptoms (Cohen's d = 0.61) than for atypical symptoms (Cohen's d = 0.41), and improvements persisted at day three. The findings suggest ketamine may have early preferential effects on typical/melancholic symptoms, though it benefits both symptom dimensions.

Study at a glance

Characteristics Double-blind, placebo-controlled, crossover study Peer reviewed
Sample size 68
Population Participants with treatment-resistant major depressive disorder or bipolar depression
Intervention Ketamine
Dose a single intravenous dose
Duration Up to 14 days postinfusion
Topics Depression Ketamine
Keywords Placebo Melancholic depression Rating scale Depression economics
Citations 23
Key finding Ketamine improved both typical/melancholic and atypical depressive symptoms, with greater early effects on typical/melancholic symptoms.

Abstract

OBJECTIVE: Ketamine's effects on different dimensions of depressive symptomatology, including typical/melancholic and atypical depression, remain largely unknown. This study examined the effects of a single intravenous dose of ketamine on general depressive symptoms (measured using the Montgomery-Asberg Depression Rating Scale (MADRS), typical/melancholic symptoms (measured using the MADRS5), and atypical symptoms (measured using the Scale for Atypical Symptoms (SAS)). METHODS: Data from 68 participants with treatment-resistant major depressive disorder (MDD) or bipolar depression were pooled from three separate, double-blind, placebo-controlled, crossover studies investigating ketamine's efficacy in depression. MDD participants were unmedicated; bipolar participants received therapeutic-dose lithium or valproate. Clinical symptoms were collected preinfusion and up to 14 days postinfusion. Effect sizes were calculated for days 1 and 3 postinfusion. The primary measures of interest for this exploratory analysis were total MADRS, MADRS5, and SAS scores. Individual symptoms were also analyzed in an exploratory manner. RESULTS: Scores improved significantly at Day 1 postinfusion (MADRS: Cohen's d = 0.64; MADRS5: Cohen's d = 0.61; SAS: Cohen's d = 0.41) and continued to be significantly improved over placebo at Day 3 (MADRS: Cohen's d = 0.49; MADRS5: Cohen's d = 0.43; SAS: Cohen's d = 0.39). Effect sizes were greater for typical/melancholic than atypical symptoms at Day 1 postinfusion. CONCLUSION: Ketamine appears to effectively treat both the typical/melancholic and atypical symptoms of depression, but may have early preferential effects for the former.

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