This open-label trial (n=24) investigates the efficacy of subcutaneous ketamine (21-42mg/70kg) for treating depression (MDD) in elderly patients.
In the first phase, participants with major depressive disorder (MDD) receive single doses of 0.3mg/kg and 0.6mg/kg ketamine in order, with a one-week gap. Phase 2 involves eligible patients from Phase 1 receiving 1-2x weekly ketamine dosing for up to 3 months based on their response.
The primary outcome is the change in depression rating scale (GDS: Geriatric Depression Scale) at 24 hours post-dose. Secondary outcomes include GDS scores in Phase 2.
The study, named KED (Ketamine Elderly Depression), is non-randomised, recruiting participants aged over 65. It aims to address the dearth of evidence-based guidelines for treating depression in elderly individuals, specifically MDDE, and evaluates the role of ketamine in achieving rapid anti-depressant effects.
The trial is registered on ANZCTR with registration number ACTRN12617001130358. It was submitted on 27/07/2017, registered on 2/08/2017, last updated on 17/07/2018, and has received ethics approval from the Southern Health and Disability Committee in New Zealand on 30/01/2018.
The study is still recruiting, with the anticipated dates for the first participant enrolment, last participant enrolment, and last data collection being 24/09/2018, 31/12/2019, and 30/04/2020, respectively.
The University of Otago is the primary sponsor, funding the research. Principal investigator A/Prof Yoram Barak is leading the study to evaluate ketamine’s effects on depression ratings, safety, and the potential for sustaining improvements in elderly patients with MDD.
Trial Details
Major depressive disorder in the elderly (MDDE) can often present as a severe form of MDD associated with suicide, longer inpatient stay and overall worse prognosis than other forms of MDD. Furthermore, In a US study of hospitalized participants with MDD, 25% met the criteria for MDD with psychotic features and this was even more prevalent amongst the elderly (Coryell et al., 1984). Elderly MDDE patients present a unique treatment challenge to clinicians, since they often exhibit needs quite different from those of MDD patients due to substantial physical comorbidity and variations in response to therapy. MDDE is probably heterogeneous and its aetiopathogenesis is complex. Treatment of MDDE is currently only loosely based on guidelines. Unfortunately, there is a considerable dearth of literature involving evidence-based clinical practice guidelines and randomized controlled trials in individuals with MDDE. Treatment guidelines for MDDE are lacking and the evidence is limited regarding the most effective pharmacological treatment. Furthermore, there are only a small number of treatment studies in elderly patients with psychotic depression. The rates of MDDE with psychotic features are higher in the elderly and they respond poorly to treatment with medication (Kok et al., 2010; Croucher et al., 2017). This year two reports emphasized the need to study the role of Ketamine in MDDE. Ketamine is a dissociative anaesthetic, which provides antagonism on the N-methyl-D-aspartate (NMDA) receptor. Several studies have demonstrated rapid anti-depressant and anti-suicidal effects from the administration of ketamine in adult patients (Katalinic, 2013) but studies in MDDE are few. A case report on a patient in late life who suffered from treatment-resistant MDDE and was treated with ketamine achieving remission has been published recently (Heard et al., 2017). An additional encouraging report focused on MDDE patients treated by ECT. Although ECT has been shown to be efficacious in depressed older adults, a subgroup of patients may show either limited or no response to this intervention. Ketamine, has been shown to rapidly improve depressive symptoms and suicidal ideation when given in addition to ECT in the elderly (Saxena & Espinoza, 2017). There are also positive recently published safety and efficacy data in 16 elderly geriatric depressed patients from a group in Sydney, Australia, with ketamine doses ranging from 0.1 to 0.5 mg/kg (George et al., 2017). Study Objectives: 1. To evaluate the effect of ketamine on depression ratings in elderly patients with MDD. 2. To evaluate the safety and tolerability of ketamine in elderly patients with MDD 3. To evaluate the potential for repeat-dose ketamine to sustain reductions in depression in elderly patients with MDDNCT Number ACTRN12617001130358
Sponsors & Collaborators
University of OtagoThe University of Otago (specifically the Dunedin School of Medicine) is associated with psychedelic research but doesn't yet have a full profile.