Comparison of the Antianhedonic Effects of Repeated-dose Intravenous Ketamine in Older and Younger Adults with Major Depressive Episode.
Wei Zheng, Limei Gu, Jianqiang Tan, Yanling Zhou, Chengyu Wang, Xiaofeng Lan, Bin Zhang, Zezhi Li, Yuping Ning
Current Neuropharmacology 2025 DOI: 10.2174/1570159X23666240923112548 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label clinical trial Peer reviewed |
|---|---|
| Sample size | 135 |
| Population | Patients with major depressive episodes |
| Intervention | Intravenous ketamine |
| Dose | 0.5 mg/kg over 40 min |
| Duration | 12-day infusion period, with follow-up to day 26 |
| Topics | Depression Ketamine Esketamine |
| Keywords | Anhedonia Major depressive disorder. Older adults Younger adults Mental health Depression treatment Ketamine therapy Age differences Clinical research |
| Citations | 1 |
| Key findings | Older depressed patients had a lower antianhedonic response to repeated-dose intravenous ketamine than younger adults, with no older patients achieving remission. |
Abstract
Growing evidence suggests that repeated-dose intravenous ketamine in patients with depression had rapid antianhedonic effects. However, a comparison of the antianhedonic effects of repeated-dose intravenous ketamine between younger adults and older depressed patients has not been examined. To the best of my knowledge, this study with a total of 135 patients with major depressive episodes (MDE) is the first to compare the antianhedonic effects between younger adult (n = 116) and older (n = 19) depressed patients receiving six ketamine infusions (0.5 mg/kg over 40 min). Montgomery- Åsberg Depression Rating Scale (MADRS) was applied in this study to evaluate the clinical symptoms, and MADRS anhedonia item scoring was used to evaluate anhedonia symptoms. Patients received six open-label intravenous infusions of ketamine for 12 days. MADRS anhedonia subscale scores decreased in both younger (3.3, 95% CI = 2.5-4.1, p < 0.05) and older (2.8, 95% CI = 1.1-4.6, p < 0.05) MDE patients at 4h after the first infusion compared to baseline scores and the reduction was maintained over the subsequent infusion period in both groups (all Ps < 0.05). Younger MDE patients had lower MADRS anhedonia subscale scores on day 26 compared with older patients (P = 0.02). Compared with younger adult MDE patients, older patients had a lower antianhedonic response (51.7% [95% CI = 42.5%-61.0%] versus 31.6% [95% CI = 8.6%-54.6%)] and remission (24.1% [95% CI = 16.2%-32.0%] versus 0%). This study indicates that repeated-dose intravenous ketamine administration induces rapid and robust antianhedonic effects in older MDE patients. However, older MDE patients displayed less response to ketamine than younger adult MDE patients.