Subcutaneous ketamine infusion in palliative patients for major depressive disorder (SKIPMDD)-Phase II single-arm open-label feasibility study.

BACKGROUND

Ketamine at subanaesthetic dosages (≤0.5mg/kg) exhibits rapid onset (over hours to days) antidepressant effects against major depressive disorder in people who are otherwise well. However, its safety, tolerability and efficacy are not known for major depressive disorder in people with advanced life-limiting illnesses.

OBJECTIVE

To determine the feasibility, safety, tolerability, acceptability and any antidepressant signal/activity to justify and inform a fully powered study of subcutaneous ketamine infusions for major depressive disorder in the palliative setting.

METHODS

This was a single arm, open-label, phase II feasibility study (Australian New Zealand Clinical Trial Registry Number-ACTRN12618001586202). We recruited adults (≥ 18-years-old) with advanced life-limiting illnesses referred to four palliative care services in Sydney, Australia, diagnosed with major depressive disorder from any care setting. Participants received weekly subcutaneous ketamine infusion (0.1-0.4mg/kg) over two hours using individual dose-titration design. Outcomes assessed were feasibility, safety, tolerability and antidepressant activity.

RESULTS

Out of ninety-nine referrals, ten participants received ketamine and were analysed for responses. Accrual rate was 0.54 participants/month across sites with 50% of treated participants achieving ≥ 50% reduction in baseline Montgomery-Åsberg Depression Rating Scale, meeting feasibility criteria set a priori. There were no clinically relevant harms encountered.

CONCLUSIONS

A future definitive trial exploring the effectiveness of subcutaneous infusion of ketamine for major depressive disorder in the palliative care setting may be feasible by addressing identified study barriers. Individual dose-titration of subcutaneous ketamine infusions over two hours from 0.1mg/kg can be well-tolerated and appears to produce transient antidepressant signals over hours to days.

Informations de copyright

Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

CS is the recipient of the Sydney Partnership for Health, Education, Research and Enterprise (SPHERE) Palliative Care Clinical Academic Group Seed Grants. RC receives consulting fees or payments from Cymra Life Sciences Limited, Tilray Australia and New Zealand, AstraZeneca Pty Limited, A. Menarini Australia Pty Ltd. RC also receives payments for expert testimony from Office of the Director of Public Prosecutions NSW. AB assists in running a tertiary referral ketamine service at Black Dog Institute, running the Spravato (intranasal esketamine) early access program, and acting as a site principal investigator on a related quality of life study. CL participated in Janssen Advisory Board, acted as an unpaid consultant for Douglass Pharmaceuticals, and received support from Royal Australian and New Zealand College of Psychiatrists (RANZCP) for presenting at RANZCP Congress. DC is a paid consultant and advisory board member for Helsinn Pharmaceuticals, a paid consultant for Mayne Pharma International Pty Ltd, a paid subcontractor for Nous Group Pty Ltd, a paid board member for Icare Dust Diseases Board, and unpaid consultants for Chris O’Brien Lifehouse and Illawarra Health and Medical Research Institute (IHMRI). DC also receives payment from Mayne Pharma International Pty Ltd for intellectual property. Other authors declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.