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Oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized placebo-controlled multicentre trial of KET01, a novel ketamine formulation - Clinical and safety results.

Michael Colla, Benjamin Offenhammer, Hanne Scheerer, Golo Kronenberg, Stefan Vetter, J Mutschler, T Mikoteit, Anna Bankwitz, Atalìa Adank, Linda Schaekel, Corinne Eicher, Annette B Brühl, Erich Seifritz

Journal of Psychiatric Research May 1, 2024 DOI: 10.1016/j.jpsychires.2024.03.002 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Placebo-controlled Double-blind Peer reviewed
Sample size 27
Population Patients suffering from treatment-resistant depression
Intervention Placebo
Dose 160 mg/day or 240 mg/day
Duration 14-day intervention
Topics Depression Esketamine Ketamine
Keywords Ketamine therapy Mental health treatment Clinical trials Antidepressants
Citations 23
Key findings Adjunctive oral prolonged-release ketamine at 240 mg/day showed a positive but statistically non-significant trend towards antidepressant efficacy in treatment-resistant depression.

Abstract

We investigated the antidepressant effects of a novel oral prolonged-release formulation of racemic ketamine (KET01) in patients suffering from treatment-resistant depression (TRD) as add-on therapy. Patients were randomized to an additional 160 mg/day or 240 mg/day KET01 or placebo for 14 days. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to day 15. For treatment group comparisons, we used ANOVA with pairwise least squares mean difference tests in a mixed model repeated measures analysis. Twenty-seven patients completed the double-blind protocol before trial premature termination due to poor recruitment during the COVID-19 pandemic. Mean (SD) MADRS scores on day 15 were 23 (10.32) in placebo, 25 (8.28) with 160 mg/day and 17 (10.32) with 240 mg/day KET01. MADRS change was numerically larger but statistically non-significant in the 240 mg/day KET01 group vs placebo on day 7 (-5.67; p = 00.106) and day 15 was (difference: 4.99; p = 00.15). In exploratory analysis, baseline leukocyte count correlated with response to KET01 (p = 00.01). Distribution of adverse event rates were comparable between the treatment arms. Safety analysis did not identify increased risk of suicidality, dissociation, hear rate, systolic and diastolic blood pressure associated with trial treatment. Our results suggest that adjunctive oral administration of prolonged-release ketamine at a dose of 240 mg/day shows a positive, although statistically non-significant, trend towards antidepressant efficacy, however, the benefit could not be confirmed due to premature trial termination. Given its ease of use and low side effects, further trials are warranted to investigate this route of ketamine administration as a promising potential treatment of TRD.

Comparable studies

Other randomized controlled trials on ketamine for depression, most cited first.

Study Year Design Participants
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68

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