Effect of continuous esketamine infusion on brain white matter microstructure in patients with major depression: A diffusion tensor imaging study.
Xiang Liu, Zhipeng Wei, Lifeng Li, Jiangping Li, Yingke Deng, Yumeng Liu, Haijun Li, Dechang Peng, Xin Wan, Guojiang Wu
Journal of Affective Disorders March 1, 2025 DOI: 10.1016/j.jad.2024.12.002 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | Patients with major depressive disorder and healthy controls |
| Intervention | Esketamine |
| Dose | 0.25 mg/kg intravenous |
| Duration | 2-week treatment |
| Topics | Depression Esketamine |
| Keywords | Antidepressants antidepressant medication Depression medication Mood medication Esketamine ketamine therapy Ketamine treatment Intranasal ketamine Severe depression |
| Citations | 12 |
| Key findings | Short-term esketamine treatment improved depressive symptoms but did not reverse the compromised white matter fiber integrity observed in patients with major depressive disorder. |
Abstract
Esketamine has demonstrated acute antidepressant effects in patients with major depressive disorder (MDD). This study investigated whether these effects associate with reversible white matter fiber integrity recovery using diffusion imaging. Twenty patients with MDD and 20 healthy controls received 2-week esketamine treatment. Patients received 0.25 mg/kg intravenous esketamine. Emotional and cognitive recovery were assessed. Diffusion tensor imaging and tract-based spatial statistics evaluated white matter fiber integrity pre/post-treatment. Correlation analyses examined associations between white matter changes and clinical scales. Compared to controls, patients with MDD exhibited decreased fractional anisotropy (FA) values of cerebral white matter fibers involving the association fibers, the commissural fibers and projection fibers. Esketamine effectively reduced depression, anxiety, and suicidal ideation scores while improving cognitive function. However, no reversible recovery of compromised white matter integrity was observed after 2 weeks of esketamine treatment. FA reductions in projection fibers correlated with anxiety and suicidal ideation severity. Concurrent sertraline use and lack of placebo control limited our ability to isolate esketamine's effects. The wide age range may have introduced response variability. We used minimal effective dosages based on previous research. The small sample size limited statistical power. Larger, more controlled studies are needed to validate these preliminary findings. This study enhances MDD neuropathological understanding, with widespread white matter impairment and associations between projection fibers and symptom severity. While producing significant antidepressant effects, short-term esketamine did not recover compromised white matter microstructure.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 4
- Effects of Binaural Beat Music and Esketamine for ECT in the Treatment of Major Depressive Disorder: A Randomized Controlled Trial Protocol. Neuropsychiatric Disease and Treatment 2025
- Structural Neurotoxic and Neuroprotective Effects of Ketamine and Esketamine in Preclinical and Human Studies: A Systematic Review Research Square May 27, 2026
- Multiple peripheral inflammatory markers in adolescents with major depressive disorder treated with repeated esketamine infusions: results from a randomized controlled trial. Journal of Affective Disorders February 23, 2026
- Potential molecular pathways and therapeutic implications of rapid-acting antidepressants on myelin biology: a scoping review. Frontiers in Neuroscience 2025
Cites 10
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II) The International Journal of Neuropsychopharmacology August 26, 2020
- Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Journal of Affective Disorders September 23, 2020
- Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent The Journal of Clinical Psychiatry May 11, 2020
and 5 more in the library