A Pilot Study of Ketamine Infusion after Suicide Attempt: New Frontiers in Treating Acute Suicidality in a Real-World Medical Setting.

Ketamine, in research settings, rapidly reduces suicidal thoughts 2-24 h after a single infusion in patients with high suicidal ideation. In this study, the authors investigate ketamine's effects on suicidality in a real-world sample of recent suicide attempters on a tertiary-care Consultation-Liaison (CL) psychiatry service. Using an open-label design, 16 transdiagnostic CL patients were recruited, 18-65 years old, to receive a single dose of intravenous ketamine (0.5 mg/kg) in the acute medical setting. All were psychiatrically hospitalized post-infusion. Baseline suicidality and depression measures were compared to ratings taken at 24 h, 5 days, 12 days, and 1, 3 and 6 months post-infusion using paired t-tests. Across all measures, rapid, statistically significant decreases (p's < 0.001) were observed with large to very large effect sizes (Cohen's d's: 1.7-8.8) at acute timepoints (24 h; 5 days). These gains were uniformly maintained to 6 months post-infusion. Open-label ketamine appeared to rapidly and robustly reduced suicidal symptoms in an ultra-high-risk, heterogeneous, real-world sample. Ketamine infusion may therefore be a safe, feasible, viable method to rapidly reduce suicidality among medically hospitalized patients after a suicide attempt, with potentially enduring benefits. The current pilot findings suggest ketamine could be readily integrated into the settings where high-risk CL patients already receive healthcare, with the potential to become an important and novel tool in the treatment of suicidality.

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators.

Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials [pooled n = 809]. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median = 55.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute [~24-hours; ß*(95% CI) = 0.58 (0.44, 0.72); p < 0.0001] and post-acute [~7 days; ß*(95% CI) = 0.38 (0.23, 0.54); p < 0.0001] depression severity were observed. Two study-level moderators emerged as significant: ketamine effects (relative to placebo) were larger in studies that required a higher degree of previous treatment resistance to federal regulatory agency-approved antidepressant medications (≥2 failed trials) for study entry; and in studies that used a crossover design. A comprehensive data-driven search for combined moderators identified statistically significant, but modest and clinically uninformative, effects (effect size r ≤ 0.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions.Review Registration: PROSPERO Identifier: CRD42021235630.