1 Lee W, et al. BMJ Open 2021;11:e052312. doi:10.1136/bmjopen-2021-052312 Open access Study protocol for SKIPMDD: subcutaneous ketamine infusion in palliative care patients with advanced life limiting illnesses for major depressive disorder (phase II pilot feasibility study) Wei Lee, 1,2 Caitlin Sheehan, 3 Richard Chye, 4,5 Sungwon Chang, 1 Colleen Loo, 6,7 Brian Draper, 7 Meera Agar, 1 David C Currow 1,8 To cite: Lee W, Sheehan C, Chye R, et al. Study protocol for SKIPMDD: subcutaneous ketamine infusion in palliative care patients with advanced life limiting illnesses for major depressive disorder (phase II pilot feasibility study). BMJ Open 2021;11:e052312. doi:10.1136/ bmjopen-2021-052312 ► Prepublication history for this paper is available online. To view these files, please visit the journal online (http://dx.doi. org/10.1136/bmjopen-2021- 052312). Received 14 April 2021 Accepted 10 June 2021 For numbered affiliations see end of article. Correspondence to Dr David C Currow; David.Currow@uts.edu.au Protocol © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. ABSTRACT Introduction Major depressive disorder (MDD) in people with advanced life-limiting illnesses can have significant impact on the quality-of-life of those affected. The management of MDD in the palliative care setting can be challenging as typical antidepressants may not work in time nor be tolerated due to coexisting organ dysfunctions, symptom burden and frailty. Parenteral ketamine was found to exhibit effective and rapid-onset antidepressant effect even against treatment-resistant depression in the psychiatric population. However, there is currently neither feasibility study nor available prospective study available to inform of the safety, tolerability and efficacy of such for MDD in the palliative setting. Methods and analysis This is an open-labelled, single arm, phase II pilot feasibility study involving adult patients with advanced life-limiting illnesses and MDD across four palliative care services in Australia. It has an individual dose-titration design (0.1–0.4 mg/kg) with weekly treatments of subcutaneous ketamine infusion over 2 hours. The primary outcome is feasibility. The secondary outcomes are related to the safety, tolerability and antidepressant efficacy of ketamine, participants’ satisfaction in relation to the trial process and the reasons for not completing the study at various stages. The feasibility data will be reported using descriptive statistics. Meanwhile, side effects, tolerability and efficacy data will be analysed using change of assessment scores from baseline. Ethics and dissemination Ethics approval was acquired (South Western Sydney Local Health District: HREC/18/ LPOOL/466). The results of this study will be submitted for publication in peer-reviewed journals and presented at relevant conferences. Trial registration number Australian New Zealand Clinical Trial Registry Number: ACTRN12618001586202; Pre-results. INTRODUCTION Major depressive disorder (MDD) is common and can be severely distressing in individ- uals with advanced life-limiting illnesses. It affects approximately 10%–15% of individ- uals in the palliative care setting. 1–3 MDD can significantly impact the quality-of-life of those affected and may be associated with a sense of worthlessness and the desire for hastened death. 4–7 The assessment and management of MDD can be challenging in the palliative care setting, particularly in the presence of substantial medical comorbidities when the prognosis is limited to only days to weeks. Strengths and limitations of this study ► This study may provide key feasibility information for a future definitive study in the palliative care set- ting and inform the safety, tolerability and the anti- depressant activity of ketamine for this population. ► Subcutaneous ultralow-dose infusion (<0.5 mg/kg) via an individually tailored dose titration design will likely maximise acceptability and tolerability for pal- liative patients, though there is less evidence for this approach compared with the conventional ketamine administration regimen (intravenous 0.5 mg/kg). ► The use of Endicott criteria for the diagnosis of ma- jor depressive disorder in the palliative care setting reduces the confounding effects of symptoms of terminal illnesses. ► The use of standard psychiatry research instruments allows direct comparison of this trial with other psy- chiatric trials, while maintaining the use of familiar oncological and palliative care trial instruments for safety monitoring. ► Inability to inform definitive effectiveness of ket- amine (not blinded randomised controlled trial). on February 19, 2022 by guest. Protected by copyright. http://bmjopen.bmj.com/ BMJ Open: first published as 10.1136/bmjopen-2021-052312 on 28 June 2021. Downloaded from