Dataset Information

Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Benefits, and Effect on Cognition.

ABSTRACT:

Objective

Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults.

Methods

In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this acute phase were eligible to receive weekly infusions for 4 more weeks in a continuation phase. Acceptability, tolerability, and safety, including adverse and serious adverse events (AEs and SAEs), blood pressure changes, dissociation, craving, in addition to rates of depression response and remission were evaluated. The NIH Toolbox Cognitive Battery was used to assess specific measures of executive function (EF) and overall fluid cognition.

Results

Completion rates were 88% for the acute phase and 100% for the continuation phase. No AEs resulted in participant discontinuation, and there were no SAEs. Treatment-emergent elevation of blood pressure, dissociation, and craving were transient and did not result in any participant discontinuation. Depressive symptoms improved significantly and 48% of participants responded. During the acute phase, the EF measures and the fluid cognition composite score improved (Cohen's d = 0.61), and these improvements were sustained in the continuation phase.

Conclusion

This pilot study suggests that repeated IV ketamine infusions are well-tolerated and are associated with improvement in depression and EF in older adults with TRD. These promising findings need to be confirmed and extended in a larger randomized controlled trial.

SUBMITTER: Oughli HA

PROVIDER: S-EPMC10839705 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Benefits, and Effect on Cognition.

Oughli Hanadi Ajam HA Gebara Marie Anne MA Ciarleglio Adam A Lavretsky Helen H Brown Patrick J PJ Flint Alastair J AJ Farber Nuri B NB Karp Jordan F JF Mulsant Benoit H BH Reynolds Charles F CF Roose Steven P SP Yang Lei L Butters Meryl A MA Lenze Eric J EJ

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20221205 3

<h4>Objective</h4>Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults.<h4>Methods</h4>In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this acute phase were eligible to receive weekly infusions for 4 more weeks in a continuation ph ...[more]

PMID: 36529623

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Project description:BackgroundStudies have confirmed the rapid antidepressant action of ketamine in depressive episodes. Nevertheless, a standardized procedure for the delivery of ketamine infusion in individuals suffering from treatment-resistant depression, particularly in terms of infusion frequency and total dosage, remains undetermined. In addition, an efficacious ketamine regimen for persistent pain management involved a continuous 10-day infusion period with no notable adverse effects. Consequently, the primary objective of this study was to evaluate the antidepressant capacity of consecutive ketamine infusions spanning over three successive days, the duration of therapeutic response, and the overall safety profile of the treatment.MethodsIn this randomized controlled trial, participants aged 18-64 with treatment-resistant depression were randomized to receive either intravenous ketamine or midazolam (used as an active placebo) for 40 min daily over three consecutive days. Statistical analysis using repeated measures ANOVA was employed to assess the changes in the total score of the Montgomery-Åsberg Depression Rating Scale (MADRS) and the clinical global impression-Severity from the initial assessment to 10 and 31 days post-infusion. Additionally, the duration of response and remission was evaluated using Kaplan-Meier survival analysis.ResultsOut of 33 randomized participants, 20 underwent the treatment as planned. By day 10th, the ketamine group had a mean reduction in MADRS score of 12.55 (95% CI = 6.70-18.09), whereas the midazolam group had a decrease of 17.22 (95% CI = 11.09-23.36). This pattern continued to day 31, with ketamine showing a mean score decrease of 13.73 (95% CI = 7.54-19.91) and midazolam a fall of 12.44 (95% CI = 5.61-19.28). Both treatments were well tolerated, with dissociative symptoms in the ketamine group being temporary and ceasing by the end of each infusion.ConclusionIntravenous ketamine given for three consecutive days did not show a notable antidepressant advantage when compared to the active placebo midazolam, highlighting the need for further research into effective treatments schedules for treatment-resistant depression.Trial registrationNCT05026203, ClinicalTrials.gov, registered on 24/08/2021.

Project description:BackgroundIntravenous (IV) ketamine and intranasal (IN) esketamine have been studied as novel alternatives to manage treatment-resistant depression (TRD). The objective of this observational pilot study is to compare the real-world effectiveness and tolerability of IV ketamine and IN esketamine in the management of unipolar TRD.ObjectiveTo compare the effectiveness (primary outcome measure) and tolerability (secondary outcome measure) of racemic ketamine and esketamine in the management of TRD in adults and provide an expert qualitative commentary on the application of IV ketamine and IN esketamine in clinical practice (exploratory objective), focusing on the recruitment process, patient retention, effectiveness, and tolerability of the treatments.MethodsThis is a multicenter prospective observational study of naturalistic clinical practice. We expect to recruit 10 patients per treatment arm-IV ketamine or IN esketamine per center (2 centers, total 40 subjects). Patients experiencing moderate to severe TRD and who are candidates for receiving low-dose IV ketamine treatments or IN esketamine as part of their standard-of-care treatments will be recruited. We will measure the effectiveness of each treatment arm by measuring the severity of depression symptoms using the Montgomery and Åsberg Depression Rating Scale; tolerability, side effects, and the appearance of dissociation symptoms using the simplified 6-item version of the Clinician Administered Dissociative Symptom Scale (CADSS-6); and potential for abuse using a Likeability and Craving Questionnaire. Logistic regression will examine odds ratios, number needed to treat for response and remission, number needed to harm, and likelihood to be helped or harmed of each treatment. Covariate analysis will assess the impact of site and demographic variables on treatment efficacy.ResultsThis observational trial was approved by the Queen's University Health Science and Affiliated Teaching Hospital's Research Ethics Board in February 2021. The two research centers involved have started patient recruitment. Our research center (Providence Care Hospital, Kingston, Ontario) has recruited 9 patients so far. We expect to finalize data gathering by August 2022. The manuscript is expected to be published by December 2022.ConclusionsWe hypothesize that both treatments will have comparable rapid and robust antidepressant effects and similar tolerability profiles in a real-world setting for the management of TRD.International registered report identifier (irrid)DERR1-10.2196/34711.

Dataset Information

Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Benefits, and Effect on Cognition.

Objective

Methods

Results

Conclusion

Publications

Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Benefits, and Effect on Cognition.

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