Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Nov;142(5):394-401.
doi: 10.1111/acps.13216. Epub 2020 Aug 6.

The effects of ketamine on typical and atypical depressive symptoms

L T Park  1 , D A Luckenbaugh  1   2 , S J Pennybaker  1   3 , M A Hopkins  1   4 , I D Henter  1 , M S Lener  1   5 , B Kadriu  1 , E D Ballard  1 , C A Zarate Jr  1
Affiliations
Randomized Controlled Trial

The effects of ketamine on typical and atypical depressive symptoms

L T Park et al. Acta Psychiatr Scand. 2020 Nov.

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.

Keywords: appetite; atypical depression; ketamine; melancholic depression; sleep.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

All other authors have no conflict of interest to disclose, financial or otherwise.

Figures

Fig. 1.
Fig. 1.
Effect size of ketamine on MADRS, MADRS5, and SAS total scores. MADRS, Montgomery–Asberg Depression Rating Scale; SAS, Scale for Atypical Symptoms.
Fig. 2.
Fig. 2.
Effect size of ketamine on MADRS and SAS individual items at days 1 and 3. MADRS, Montgomery–Asberg Depression Rating Scale; SAS, Scale for Atypical Symptoms. *Indicates P ≤ 0.05, not Bonferroni corrected.
See this image and copyright information in PMC

References

    1. Robertson HA, Lam RW, Stewart JN, Yatham LN, Tam EM, Zis AP. Atypical depressive symptoms and clusters in unipolar and bipolar depression. Acta Psychiatr Scand 1996;94:421–427. - PubMed
    1. Nierenberg AA, Alpert JE, Pava J. Course and treatment of atypical depression. J Clin Psychiatry 1998;59(Suppl 18):5–9. - PubMed
    1. West ED, Dally PJ. Effects of iproniazid in depressive syndromes. Br Med J 1959;1:1491–1494. - PMC - PubMed
    1. Sargant W. Some newer drugs in the treatment of depression and their relation to other somatic treatments. Psychosomatics 1960;1:14–17.
    1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th edn. Arlington, VA: Author; 2013.

Publication types