None listed
Conditions
Brief summary
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 MDD
Interventions
Phase 1: Open label subcutaneous (SC) ketamine (single doses of 0.3 and 0.6 mg/kg, in that order) in patients with major depressive disorder (MDD) (n=24). All patients will receive both the 0.3mg/kg and the 0.6mg/kg dose in that order, duration between the two doses will be one week. Phase 2: Patients completing Phase 1 and who had at least 50% reduction in depression ratings - reduction in score on the Geriatric Depression Scale (GDS) - in response to any dose of ketamine are eligible to recei
Phase 1: Open label subcutaneous (SC) ketamine (single doses of 0.3 and 0.6 mg/kg, in that order) in patients with major depressive disorder (MDD) (n=24). All patients will receive both the 0.3mg/kg and the 0.6mg/kg dose in that order, duration between the two doses will be one week. Phase 2: Patients completing Phase 1 and who had at least 50% reduction in depression ratings - reduction in score on the Geriatric Depression Scale (GDS) - in response to any dose of ketamine are eligible to receive 1-2x weekly ketamine dosing for up to 3 months to help maintain improvement in depression symptoms. Subcutaneous doses administered at individualised dose, frequency (1-2 times per week) and duration (up to 3 months) will be at the discretion of the treating physician based on phase 1 response.
Sponsors
University of Otago
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be included in the study, participants must meet all of the following inclusion criteria: 1. Capable of understanding and signing an informed consent 2. Aged > 65 years on the day of consent. 3. Psychiatric history: Participants will be assessed using DSM-5 criteria (APA, 2013) via a standardized clinical psychiatric interview conducted by a trained examiner. 4. Patients with MDD: Baseline GDS > 9.
Exclusion criteria
To be included in the study, participants must meet none of the following exclusion criteria: 1. Participants who, in the opinion of the investigator, do not understand the information and procedures of the study, or would not be compliant with them (in particular the study restrictions and risks involved). 2. Any participant for whom the investigator believes, for any reason, that participation would not be an acceptable risk. 3. Patients with severe unstable acute or chronic medical illnesses. 4. Patients with current active suicidal ideation. 5. Any history of an additional axis I diagnosis (not including adjustment disorder, simple phobia, dysthymia or comorbid anxiety) is exclusionary.
Outcome results
None listed