The study protocol for SKIPMDD, a phase II pilot feasibility study to inform the safety, tolerability and efficacy of ketamine subcutaneous infusion for major depressive disorder (MDD) in patients with advanced life-limiting illnesses, was published in BMJ Open.
While there are data to support the effectiveness and rapid-onset antidepressant effect of parenteral ketamine for patients with treatment-resistant depression, there are no studies that have determined the feasibility, safety, tolerability, or efficacy of ketamine subcutaneous infusion for MDD in patients with advanced life-limiting illnesses.
This open-label, single arm, phase II pilot feasibility study will include adults from 4 palliative care services in Australia with advanced life-limiting illnesses and MDD diagnosed by Endicott criteria.
The study is set to include an individual dose-titration design with all participants receiving ketamine subcutaneous infusion. It will include a 4-week ketamine administration period, as well as a 4-week follow-up period.
All participants will receive initial subcutaneous infusion of 0.1 mg/kg ketamine over 2 hours, with dosing escalation at 0.1 mg/kg increment on a weekly interval if there is a lack of response. Up to 4 doses are allowed, with a maximal dose 0.4 mg/kg. The responses to parenteral ketamine will be regularly monitored at a predetermined schedule.
If deemed appropriate for the clinical needs of the patient, treatment with a typical antidepressant will be started or have a modified dose after initiating ketamine treatment.
The primary outcome is feasibility, measured as absolute numbers and proportions of patients who completed the study. The secondary outcomes are related to the safety, tolerability and antidepressant efficacy of ketamine, and participants’ satisfaction.
A sample size of 32 over 2 years is projected to be an appropriate number to inform study feasibility.
This study protocol has several limitations, including the study design, as this will not be a blinded randomized-controlled trial and no control group will be included. Additional limitations include the exclusion of severely depressed patients, potential confounding effect of antidepressants, and inability to escalate ketamine dose to the conventional level of 0.5 mg/kg.
“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,” concluded the study researchers.
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. Published online June 28, 2021. doi:10.1136/bmjopen-2021-052312