Neurocognitive effects of subanesthetic serial ketamine infusions in treatment resistant depression.
Artemis Zavaliangos-Petropulu, Shawn M. Mcclintock, Jacqueline Khalil, S. Joshi, Brandon Taraku, Noor B. Al-Sharif, Randall Espinoza, Katherine L Narr
Journal of Affective Disorders April 1, 2023 DOI: 10.1016/j.jad.2023.04.015 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 66 |
| Population | Patients with treatment-resistant depression |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | Four infusions over an unspecified period, with assessments at baseline, 24 hours after the first and fourth infusions, and 5 weeks after the end of treatment |
| Topics | Depression Esketamine Ketamine |
| Citations | 16 |
| Key findings | Ketamine treatment leads to improvements in neurocognitive function that persist for at least five weeks and are independent of antidepressant response. |
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.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |