Neurocognitive effects of subanesthetic serial ketamine infusions in treatment resistant depression

Artemis Zavaliangos-Petropulu; Shawn M McClintock; Jacqueline Khalil; Shantanu H Joshi; Brandon Taraku; Noor B Al-Sharif; Randall T Espinoza; Katherine L Narr

doi:10.1016/j.jad.2023.04.015

Neurocognitive effects of subanesthetic serial ketamine infusions in treatment resistant depression

J Affect Disord. 2023 Jul 15:333:161-171. doi: 10.1016/j.jad.2023.04.015. Epub 2023 Apr 14.

Authors

Artemis Zavaliangos-Petropulu¹, Shawn M McClintock², Jacqueline Khalil³, Shantanu H Joshi³, Brandon Taraku³, Noor B Al-Sharif³, Randall T Espinoza⁴, Katherine L Narr⁵

Affiliations

¹ Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA. Electronic address: azavalia@g.ucla.edu.
² Division of Psychology, Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA.
³ Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
⁴ Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
⁵ Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA; Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.

PMID: 37060953
DOI: 10.1016/j.jad.2023.04.015

Abstract

Introduction: Ketamine treatment prompts a rapid antidepressant response in treatment-resistant depression (TRD). We performed an exploratory investigation of how ketamine treatment in TRD affects different cognitive domains and relates to antidepressant response.

Methods: Patients with TRD (N = 66; 30 M/35F; age = 39.5 ± 11.1 years) received four ketamine infusions (0.5 mg/kg). Neurocognitive function and depressive symptoms were assessed at baseline, 24 h after the first and fourth ketamine infusion, and 5 weeks following end of treatment. Mixed effect models tested for changes in seven neurocognitive domains and antidepressant response, with post-hoc pairwise comparisons between timepoints, including follow-up. Relationships between change in neurocognitive function and antidepressant response over the course of treatment were tested with Pearson's correlation and mediation analyses. Associations between baseline neurocognitive performance and antidepressant response were tested with Pearson's correlation.

Results: Significant improvements in inhibition, working memory, processing speed, and overall fluid cognition were observed after the first and fourth ketamine infusion. Improvements in processing speed and overall fluid cognition persisted through follow-up. Significant improvements in depressive symptoms reverted towards baseline at follow-up. Baseline working memory and change in inhibition were moderately correlated with antidepressant response, however, improvements in neurocognitive performance were statistically independent from antidepressant response.

Conclusion: Antidepressant ketamine leads to improved neurocognitive function, which persist for at least 5 weeks. Neurocognitive improvements observed appear independent of antidepressant response, suggesting ketamine may target overlapping but distinct functional brain systems. Limitations Research investigating repeated serial ketamine treatments is important to determine cognitive safety. This study is a naturalistic design and does not include placebo.

Keywords: Antidepressant; Cognition; Depression; Ketamine; Neurocognitive; Treatment.

Publication types

Clinical Trial
Research Support, N.I.H., Extramural

MeSH terms

Adult
Antidepressive Agents / adverse effects
Depression
Depressive Disorder, Treatment-Resistant* / drug therapy
Humans
Infusions, Intravenous
Ketamine* / adverse effects
Middle Aged
Treatment Outcome

Substances

Antidepressive Agents
Ketamine

Abstract

Publication types

MeSH terms

Substances

Grants and funding