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Randomized Controlled Trial
. 2024 May:173:124-130.
doi: 10.1016/j.jpsychires.2024.03.002. Epub 2024 Mar 4.

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

M Colla  1 , B Offenhammer  2 , H Scheerer  2 , G Kronenberg  2 , S Vetter  2 , J Mutschler  3 , T Mikoteit  4 , A Bankwitz  2 , A Adank  2 , L Schaekel  2 , C Eicher  2 , A B Brühl  5 , E Seifritz  2
Affiliations
Randomized Controlled Trial

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

M Colla et al. J Psychiatr Res. 2024 May.

Abstract

Introduction: 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.

Material and methods: 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.

Results: 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.

Discussion: 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.

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Conflict of interest statement

Declaration of competing interest Michael Colla reports research grants from Ketabon GmbH; and lecture fees from Recordati, Sunovion, and Lundbeck. Benjamin Offenhammer reports honoraria for creation of educational material and travel support from Takeda pharmaceuticals. Jochen Mutschler reports consulting fees from Janssen Pharmaceutica, Lundbeck AG, and Recordati; honoraria from Janssen Pharmaceutica, Lundbeck AG, Mepha; payments for Expert testimonies from Janssen Pharmaceutica and Lundbeck; travel support from Janssen Pharmaceutical, Lundbeck, and Recordati; and participation in the advisory board at Lundbeck and Janssen Pharmaceutical. Thorsten Mikoteit reports payments for participation in the advisory board at Janssen-Cilag Ltd. Annette B. Bruehl reports research grants from Ketabon GmbH; payments (institution) from Janssen Schweiz, OM Pharma, and Schwabe AG; and participation in advisory board at Janssen Schweiz. Erich Seifritz reports research grants from Ketabon GmbH and University of Zürich; advisory fees, lecture fees, unrestricted educational grants from Lundbeck Swizerland, Recordati Switzerland, Janssen Switzerland, Schwabe Switzerland and Germany, Takeda Switzerland, OM Pharma Switzerland, and Sandoz Switzerland; payment from Lundbeck Switzerland and Janssen Switzerland for testimony to the Swiss Health Ministery regarding registration of psychiatric drugs; travel support from Schwabe Pharma Switzerland; unpaid co-authorship of Swiss treatment guidelines for depression and anxiety disorders; and stock ownership for Abcellera Canada. All other authors declare no competing interests.

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