A Randomized, Double-Blind, Midazolam-Controlled Trial of Low-Dose Ketamine Infusion in Patients With Treatment-Resistant Depression and Prominent Suicidal Ideation
T. Su, Cheng-Ta Li, Wei-Chen Lin, Hui-Ju Wu, S. Tsai, Ya-Mei Bai, W. Mao, P. Tu, Li-Fen Chen, Wei-Chi Li, Mu-Hong Chen
International Journal of Neuropsychopharmacology March 26, 2023 DOI: 10.1093/ijnp/pyad014 via Semantic Scholar
Summary
A single low-dose ketamine infusion (0.5 mg/kg) produces an antidepressant effect lasting up to 14 days in outpatients with treatment-resistant depression and prominent suicidal thoughts, compared with a low-dose midazolam control. The antisuicidal effect, however, persists only 5 days. The benefits are most pronounced in patients whose current depressive episode has lasted less than 24 months or who have failed four or fewer prior antidepressants. The treatment is safe and well tolerated.
Study at a glance
| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 84 |
| Population | Outpatients with treatment-resistant depression and prominent suicidal ideation |
| Keywords | Medicine Psychology |
| Citations | 48 |
| Key finding | Low-dose ketamine provides an antidepressant effect lasting up to 14 days and an antisuicidal effect lasting 5 days, with stronger responses in patients whose current episode is shorter than 24 months or who have failed four or fewer antidepressants. |
Abstract
Abstract Background The benefits of low-dose ketamine for patients with treatment-resistant depression (TRD) and prominent suicidal ideation require further investigation. The effects of treatment refractoriness, the duration of the current depressive episode, and the number of prior antidepressant failures on ketamine efficacy also require clarification. Methods We recruited 84 outpatients with TRD and prominent suicidal ideation—defined as a score ≥4 on item 10 of the Montgomery–Åsberg Depression Rating Scale (MADRS)—and randomized them into 2 groups to receive 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. We assessed depressive and suicidal symptoms prior to infusion; 240 minutes post infusion; and 2, 3, 5, 7, and 14 days post infusion. Results According to the MADRS scores, the antidepressant effect (P = .035) was significantly noted in the ketamine group up to 14 days than in the midazolam group. However, the antisuicidal effect of ketamine, as measured by the Columbia-Suicide Severity Rating Scale Ideation Severity Subscale (P = .040) and MADRS item 10 (P = .023), persisted only 5 days post infusion. Furthermore, the antidepressant and antisuicidal effects of ketamine infusion were noted particularly in patients whose current depressive episode lasted <24 months or whose number of failed antidepressants was ≤4. Conclusions Low-dose ketamine infusion is a safe, tolerable, and effective treatment for patients with TRD and prominent suicidal ideation. Our study highlights the importance of timing; specifically, ketamine is more likely to achieve therapeutic response when the current depressive episode lasted <24 months and the number of failed antidepressants is ≤4.