Rapid Antidepressant and Antisuicidal Effects of Low-Dose Ketamine Infusion in Patients With Treatment-Resistant Depression With or Without Low-Grade Inflammation.
Mu-Hong Chen, Tung-Ping Su, Wei-Chen Lin, Cheng-Ta Li, Hui-Ju Wu, Shih-Jen Tsai, Ya-Mei Bai, Wei-Chung Mao, Pei-Chi Tu
Pharmacopsychiatry December 20, 2024 DOI: 10.1055/a-2499-7207 via PubMed
Summary
AI-generated from the abstractLow-grade inflammation (LGI) is linked to poor response to standard antidepressants, but its role in ketamine treatment for treatment-resistant depression (TRD) was unclear. In 167 patients with TRD, 46 had LGI (C-reactive protein ≥3 mg/L) and 121 did not. A single low-dose ketamine infusion improved depressive symptoms only in patients without LGI, showing no significant antidepressant effect in those with LGI. However, ketamine reduced suicidal thoughts in both groups. The placebo response was notably greater in patients with LGI, which may explain the lack of observed ketamine effect in that group. Further research is needed to confirm these findings.
Study at a glance
| Characteristics | Randomized controlled trial Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 167 |
| Population | Patients with treatment-resistant depression |
| Interventions | low-dose ketamine placebo |
| Duration | Baseline to day 3 |
| Keywords | Depression treatment Ketamine therapy Mental health Antidepressants Inflammation biomarkers |
| Citations | 1 |
| Key finding | Low-dose ketamine improved depressive symptoms only in patients with treatment-resistant depression who did not have low-grade inflammation, while its antisuicidal effect was present regardless of inflammation status. |
Abstract
Low-grade inflammation (LGI) contributes to resistance against traditional antidepressants. However, whether the antidepressant and antisuicidal effects of ketamine on patients with treatment-resistant depression (TRD) differ between those with LGI and those without LGI remains unknown.This study included 167 patients with TRD, among whom 46 had LGI and 121 did not have LGI. The patients received a single infusion of either low-dose ketamine or a placebo. A C-reactive protein level of≥3 mg/L indicated LGI. Depressive symptoms were measured from baseline to day 3 by using the 17-item Hamilton Depression Rating Scale (HDRS) and the Montgomery-Asberg Depression Rating Scale (MADRS).Generalized estimating equation models revealed antidepressant effect of ketamine in patients with no LGI (HDRS scores: p0.05). The antisuicidal effect of ketamine (indicated by the score on item 10 of the MADRS) was observed in both groups of patients with (p=0.046) and without LGI (p<0.001). However, ketamine was effective for TRD regardless of whether inflammation levels were high or low, while the placebo response was notably greater only in patients with LGI.This study suggests that among patients with TRD, only those without LGI respond to low-dose ketamine infusion. Whether the negative findings of the antidepressant effect of ketamine among patients with LGI may be because of the effect of the placebo infusion needs further investigation. Further randomized, placebo-controlled studies are needed to validate these findings.