REM density predicts rapid antidepressant response to ketamine in individuals with treatment-resistant depression.
Mina Kheirkhah, Wallace C Duncan, Qiaoping Yuan, Philip R Wang, Hamidreza Jamalabadi, Lutz Leistritz, Martin Walter, David Goldman, Carlos A Zarate, Nadia S Hejazi
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology May 1, 2025 DOI: 10.1038/s41386-025-02066-7 via PubMed
Summary
AI-generated from the abstractPeople with treatment-resistant depression show higher REM density in the first REM period and shorter REM latency than healthy volunteers, while total night REM density does not differ. Ketamine treatment reduces REM density in the first REM period but does not change total night REM density or REM latency. Baseline REM density in the first REM period moderately predicts whether a person will respond to ketamine, with higher levels indicating greater likelihood of response. This marker could help identify individuals most likely to benefit from ketamine therapy.
Study at a glance
| Characteristics | Observational cohort with intervention Peer reviewed |
|---|---|
| Sample size | 104 |
| Population | Drug-free individuals with treatment-resistant depression and healthy volunteers |
| Intervention | Ketamine |
| Topics | Depression |
| Keywords | Ketamine therapy Sleep patterns Rem sleep Mental health treatment |
| Citations | 6 |
| Registration | NCT00088699 NCT01204918 |
| Key finding | Baseline REM density in the first REM period moderately predicted antidepressant response to ketamine, with higher levels associated with greater likelihood of response. |
Abstract
Abnormalities during rapid eye movement (REM) sleep contribute to the pathophysiology of major depressive disorder (MDD), but few studies have explored the relationship between REM sleep and treatment-resistant depression (TRD). In MDD, REM sleep abnormalities often manifest as alterations in total night REM Density (RD), RD in the first REM period (RD1), and REM Latency (RL). Among these, RD1 is notably considered a potential endophenotype of depression. This study compared REM sleep markers between 63 drug-free individuals with TRD (39 F/24 M) and 41 healthy volunteers (25 F/16 M). It also investigated the effects of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, on these REM sleep variables. Specifically, the study investigated whether RD1 could predict antidepressant response to ketamine. TRD participants showed higher RD1 and shorter RL at baseline compared to HVs, as assessed via non-parametric tests, but Total Night RD did not differ between the two groups. Ketamine treatment decreased RD1 in TRD participants but did not affect Total Night RD or RL. As assessed via the Support Vector Machine (SVM) algorithm, baseline RD1 level moderately predicted antidepressant response to ketamine versus non-response (area under the receiver operating characteristic (ROC) curve (AUC) = 0.73, with a median accuracy of 0.75), wherein TRD participants with higher baseline RD1 were more likely to respond to ketamine. These results underscore the utility of RD1 for identifying individuals most likely to benefit from ketamine treatment, enabling more targeted and effective therapeutic strategies. Clinical Trials Identifier: NCT00088699, NCT01204918.