Suicidal ideation and suicide attempt following ketamine prescription in patients with treatment-resistant depression: a nation-wide cohort study
Rong Xu, Yiheng Pan, Maria Gorenflo, Pamela Davis, David Kaelber, Susan De Luca
Research Square August 7, 2023 preprint DOI: 10.21203/rs.3.rs-3207199/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective cohort study |
|---|---|
| Sample size | 321,367 |
| Population | US patients with a diagnosis of treatment-resistant depression prescribed relevant treatment, drawn from electronic health records |
| Interventions | Ketamine Esketamine |
| Duration | Follow-up from 1 day to 270 days |
| Topics | Depression Esketamine Ketamine |
| Key findings | Ketamine or esketamine prescription was associated with lower risk of suicidal ideation than other common antidepressants, with hazard ratios of 0.65 at 1-7 days, 0.78 at 1-30 days, 0.81 at 1-90 days, 0.82 at 1-180 days, and 0.83 at 1-270 days. No significant difference was observed for suicide attempts overall, except an increased 30-day risk among adolescents aged 10-24 (HR 2.22). |
Abstract
Abstract Ketamine, including esketamine, is an effective treatment for patients with treatment-resistant depression (TRD); however, its long-term efficacy in real-world populations remains poorly characterized. This is a retrospective cohort study using TriNetX US Collaborative Network, a platform aggregating electronic health records (EHRs) data from 93 million patients from 56 health care organizations in the US, and the study population includes 321,367 patients with a diagnosis of TRD who were prescribed relevant treatment in their EHRs. The prescription of ketamine (including esketamine) was associated with significant decreased risk of suicidal ideation compared to prescription of other common antidepressants: HR = 0.65 (95% CI: 0.53 – 0.81) at 1 day – 7 days, 0.78 (95% CI: 0.66 – 0.92) at 1 day – 30 days, 0.81 (95% CI: 0.70 – 0.92) at 1 day – 90 days, 0.82 (95% CI: 0.72 – 0.92) at 1 day – 180 days, and 0.83 (95% CI: 0.74 – 0.93) at 1 day – 270 days. This trend was especially robust among adults over 24 years of age, males, and White patients with TRD. No significant difference was observed for suicide attempts, except significantly increased risk for adolescents (aged 10-24) at 1 day – 30 days with HR = 2.22 (95% CI: 1.01-4.87). This study provides real-world evidence that ketamine has long-term benefits in mitigating suicidal ideation in patients with treatment-resistant depression. Future work should focus on optimizing dosage regimens for ketamine, understanding the mechanism, and the difference in various demographic subpopulations.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |