Comparative effectiveness of esketamine in the treatment of anhedonia in bipolar and unipolar depression

J Affect Disord. 2021 Jan 1;278:515-518. doi: 10.1016/j.jad.2020.09.056. Epub 2020 Sep 15.


Background: Anhedonia is a symptom associated with poorer outcomes in depression treatment, including resistance to treatment, higher functional impact and suicidality. Few drugs are known to adequately treat anhedonia in both unipolar and bipolar depression. The NMDA antagonist ketamine has been demonstrated to be effective in rapidly ameliorating anhedonia in depressive episodes. The main aim of present study is to evaluate the anti-anhedonic effect of esketamine, the S-enantiomer of ketamine recently approved for treatment-resistant depression, in unipolar and bipolar depression.

Methods: 70 patients with unipolar or bipolar depression were treated with 6 weekly subcutaneous esketamine infusions (0.5-1mg/kg). Anhedonia was measured through MADRS item 8 before and 24h after each infusion.

Results: A significant reduction in anhedonia severity was observed (p<0.0001) after 6 infusions. The effect was statistically significant 24h after the first infusion (p<0.001) in both unipolar and bipolar groups and increased with repeated infusions. Anti-anhedonic effect of esketamine did not differ between groups.

Limitations: This is an open-label, real-world study. Lack of blinding and of a placebo arm may limit the interpretation of findings.

Conclusion: Although preliminary, present findings suggest that repeated subcutaneous esketamine infusions are effective for the treatment of anhedonia in both unipolar and bipolar depressed patients. These results need to be confirmed through replication in larger double-blinded controlled trials.

Keywords: Bipolar disorder; Major depressive disorder; NMDA antagonists; Treatment-resistant depression; ketamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anhedonia
  • Antidepressive Agents / therapeutic use
  • Bipolar Disorder* / drug therapy
  • Humans
  • Ketamine* / therapeutic use


  • Antidepressive Agents
  • Esketamine
  • Ketamine