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

ABSTRACT: 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.

SUBMITTER: Shivanekar S

PROVIDER: S-EPMC9656070 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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

Shivanekar Sharvari S Shivanekar Sharvari S Gopalan Priya P Pizon Anthony A Spotts Crystal C Cruz Nicolas N Lightfoot Michael M Rohac Rebecca R Baumeister Andrew A Griffo Angela A Panny Benjamin B Kucherer Shelly S Israel Alex A Rengasamy Manivel M Price Rebecca R

International journal of environmental research and public health 20221024 21

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 medica ...[more]

PMID: 36360672

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Project description:Suicide accounts for nearly 800,000 deaths per year worldwide with rates of both deaths and attempts rising. Family studies have estimated substantial heritability of suicidal behavior; however, collecting the sample sizes necessary for successful genetic studies has remained a challenge. We utilized two different approaches in independent datasets to characterize the contribution of common genetic variation to suicide attempt. The first is a patient reported suicide attempt phenotype asked as part of an online mental health survey taken by a subset of participants (n = 157,366) in the UK Biobank. After quality control, we leveraged a genotyped set of unrelated, white British ancestry participants including 2433 cases and 334,766 controls that included those that did not participate in the survey or were not explicitly asked about attempting suicide. The second leveraged electronic health record (EHR) data from the Vanderbilt University Medical Center (VUMC, 2.8 million patients, 3250 cases) and machine learning to derive probabilities of attempting suicide in 24,546 genotyped patients. We identified significant and comparable heritability estimates of suicide attempt from both the patient reported phenotype in the UK Biobank (h2SNP = 0.035, p = 7.12 × 10-4) and the clinically predicted phenotype from VUMC (h2SNP = 0.046, p = 1.51 × 10-2). A significant genetic overlap was demonstrated between the two measures of suicide attempt in these independent samples through polygenic risk score analysis (t = 4.02, p = 5.75 × 10-5) and genetic correlation (rg = 1.073, SE = 0.36, p = 0.003). Finally, we show significant but incomplete genetic correlation of suicide attempt with insomnia (rg = 0.34-0.81) as well as several psychiatric disorders (rg = 0.26-0.79). This work demonstrates the contribution of common genetic variation to suicide attempt. It points to a genetic underpinning to clinically predicted risk of attempting suicide that is similar to the genetic profile from a patient reported outcome. Lastly, it presents an approach for using EHR data and clinical prediction to generate quantitative measures from binary phenotypes that can improve power for genetic studies.

Project description:BackgroundKetamine is approved for antidepressant therapy, but evidence regarding its use in women with perinatal depression is lacking. Herein, we investigated the effects of low-dose ketamine in women with prenatal depressive symptoms and tested the feasibility of a future large randomized trial.MethodsThis was a randomized, double-blind, placebo-controlled pilot trial. Sixty-six women with prenatal depressive symptoms who were scheduled for elective cesarean delivery were randomized to receive either low-dose ketamine (0.5 mg/kg) or placebo (normal saline). The study drugs were intravenously infused over a 40-minute period after clamping the umbilical cord. The primary outcome was depression score assessed with the Edinburgh Postnatal Depression Scale at 48 h postpartum. Among other and safety outcomes, occurrence of nausea or vomiting was observed, pain intensity was assessed with the numeric rating scale. The feasibility of implementing the protocol was also evaluated.ResultsA total of 64 parturients were included in the intention-to-treat analysis. The depression score at 48 h did not differ between groups: median 9 (interquartile range 6 to 13) with ketamine vs. 8 (6 to 10) with placebo; median difference 1, 95% CI -1 to 3; P = 0.608. The pain intensity at 4 h postpartum was less severe in the ketamine group (median difference -1, 95% CI -1 to 0, P = 0.002). Among safety outcomes, intraoperative nausea or vomiting was less common in patients given ketamine (0.0% [0/33] with ketamine vs. 21.2% [7/33] with placebo, P = 0.011). Recruitment was satisfactory and the protocol was acceptable to participants and clinicians.ConclusionsA single low-dose ketamine infusion did not decrease the depression score at 2 days, but reduced intraoperative nausea and vomiting and lowered pain intensity at 4 h after cesarean delivery among women with prenatal depressive symptoms. The study protocol is feasible for a large randomized trial.Clinical trial registrationThe study was registered with ClinicalTrials.gov (identifier: NCT03336541; 08/11/2017).

Dataset Information

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

Publications

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

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