Role of klotho on antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression and suicidal ideation.
Mu-Hong Chen, Ya-Mei Bai, Hui-Ju Wu, Cheng-Ta Li, Wei-Chen Lin, S. Tsai, T. Su, P. Tu
Journal of Affective Disorders August 1, 2023 DOI: 10.1016/j.jad.2023.08.061 via Semantic Scholar
Summary
A single low-dose ketamine infusion (0.5 mg/kg) compared to a low-dose midazolam control (0.045 mg/kg) resulted in higher serum levels of the anti-aging hormone klotho three days after treatment in 48 patients with treatment-resistant depression and strong suicidal ideation. However, ketamine did not significantly increase klotho levels from baseline, and changes in klotho were not associated with changes in depressive or suicidal symptoms. Higher baseline klotho levels predicted a poorer antidepressant response to ketamine. The findings suggest klotho may be involved in ketamine's antidepressant mechanism, but further molecular studies are needed.
Study at a glance
| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 48 |
| Population | Patients with treatment-resistant depression and strong suicidal ideation |
| Keywords | Medicine Psychology |
| Citations | 7 |
| Key finding | Ketamine did not significantly increase klotho levels, but patients receiving ketamine had higher klotho levels at Day 3 postinfusion than those receiving midazolam, and higher baseline klotho predicted poorer antidepressant response. |
Abstract
OBJECTIVE Previous studies have found an association between klotho, an anti-aging hormone, and major depressive disorder. However, whether low-dose ketamine infusion alters klotho levels among patients with treatment-resistant depression (TRD) remains unknown. METHODS In total, 48 patients with TRD and strong suicidal ideation were randomly assigned to a single 0.5 mg/kg ketamine or 0.045 mg/kg midazolam regimen and were subjected to a 2-week follow-up. Depressive and suicidal symptoms were assessed before the infusion and during the follow-up. The serum levels of klotho were assessed at baseline and 3 days postinfusion. RESULTS A generalized linear model with adjustment of baseline klotho levels showed that, despite the fact that ketamine did not significantly increase levels of klotho, patients in the ketamine group had higher levels of klotho at Day 3 postinfusion than patients in the midazolam group (p = 0.043). However, we found no association between changes in klotho levels and changes in depressive and suicidal symptoms (all p > 0.05). Higher klotho levels at baseline were associated with poorer antidepressant effect of low-dose ketamine during postinfusion follow-up. DISCUSSION Klotho may play a role in the antidepressant effect of low-dose ketamine. Additional molecular studies are necessary to elucidate the neuromechanisms of TRD, ketamine, and klotho.