None listed
Conditions
Brief summary
Depression is common in patients who have advanced life-limiting illness. There are significant time pressures for antidepressants to have rapid-onset effect in some palliative care patients. Most antidepressants, due to their slow onset of action, have limited therapeutic benefits in patients with extremely short prognoses or those with severe depression that require rapid effect while waiting for the typical antidepressants to take effect. In the psychiatry literature, subanaesthetic doses of ketamine are emerging as a novel rapid-onset antidepressant for treatment resistant major depression with high response rates, though having short-lived effect. There has been no similar trial done using ketamine to treat even de novo depression in the population with advanced life-limiting illness. There is a need to explore the activity of ketamine in palliative care patients, particularly those with very limited prognosis and/or severe depression that require immediate intervention where typical antidepressants are of limited utility for depression. Further evidence may potentially allow ketamine to be used to treat severe depression in patients with very limited but uncertain prognosis (e.g. in the range of weeks) and be considered as a bridging therapy for those who have a longer prognosis for the typical antidepressants to have effects. Prior to researchers committing to a larger phase 2/3 double blinded, cross over, randomised controlled trial, testing the activity of ketamine as antidepressant in the palliative care population, a feasibility study will be conducted with the aim to investigate: the number of patients who participate in, and subsequently complete, the ketamine intervention; the potential effects of ketamine; and the safety and tolerability of ketamine in this population. Patients known to the palliative care services in the acute hospital, palliative care units or in the community with advanced life limiting illness and major depressive disorder in Australia will be included in this study. The intervention is an individually tailored subcutaneous infusion of ketamine, given at weekly intervals by response, commencing with 0.1-0.4mg/kg over 2 hours, up to 4 doses (4 weeks) with the maximal dose of 0.4mg/kg. This is followed by 4 weeks of follow up. Commencement and titration of a typical antidepressant for depression by the treating clinical team’s choice if clinically appropriate (given 48 hours apart from ketamine administration) is allowed for ethical reasons. Primary Outcome is the number of palliative care patients completing through each stage of the study. Main secondary outcomes include serious side effects (CTCAE), psychotomimetic and dissociative symptoms (BPRS/CADSS), depression score (MADRS), quality of life score (Q-LES-Q-SF) and Numeric Pain Rating Scale.
Interventions
Individually tailored subcutaneous infusion of ketamine, at weekly intervals by response, commencing with 0.1-0.4mg/kg over 2 hours, up to 4 doses (4 weeks) with the maximal dose of 0.4mg/kg. This is followed by 4 weeks of follow up.
Commencement and titration of a typical antidepressant for depression by the treating clinical team’s choice if clinically appropriate (given 48 hours apart from ketamine administration).
Study data with its accuracy, and protocol compliance will be monitored by m
Individually tailored subcutaneous infusion of ketamine, at weekly intervals by response, commencing with 0.1-0.4mg/kg over 2 hours, up to 4 doses (4 weeks) with the maximal dose of 0.4mg/kg. This is followed by 4 weeks of follow up. Commencement and titration of a typical antidepressant for depression by the treating clinical team’s choice if clinically appropriate (given 48 hours apart from ketamine administration). Study data with its accuracy, and protocol compliance will be monitored by members of the Trial Management Committee or their delegates. Monitoring may include review of CRFs, patient’s clinical records, and being onsite to monitor protocol compliance and perform other relevant procedures.
Sponsors
University of Technology Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients known to the palliative care services in the acute hospital, palliative care units or in the community with advanced life limiting illness and major depressive disorder in Australia (inclusive of those with very limited prognosis with Australia-modified Karnofsy Performance Scale [AKPS] 30 or less, and those with severe depression with MADRS 35 or more) Inclusion criteria • Adult males or females known to palliative care service with age greater than or equal to 18 yrs • Palliative intent of treatment due to irreversible medical illnesses • Patient Health Questionnaire-2 (PHQ-2) score greater than or equal to 3, and • Major Depressive Disorder defined by Endicott Criteria diagnosed by trained personnel (e.g. psychiatry team, psychologist or trained research team member) with: • MADRS Score greater than or equal to 16 • Willing and able to comply with all study requirements, • Signed, written informed consent for the study
Exclusion criteria
Exclusion criteria • Australian-modified Karnofsky Performance scale (AKPS) score less than or equal to 10 • Having curative intent to treatment • Palliative intent life prolonging measures such as target therapies, radiotherapy or intravenous antibiotics is acceptable • Methylphenidate use in the last 4 weeks • Changes to antidepressant doses in the last 2 weeks prior to the commencement of ketamine • Ketamine use in the last 4 weeks • Previous significant adverse effect or hypersensitivity to ketamine • Concurrent phenobarbitone use • Factors of increased risk of intracranial pressure: i. Recent ischaemic or haemorrhagic cerebral vascular accident in the last 1 month ii. Brain tumours with symptoms and signs of increased intracranial pressure iii. Seizure in the last 6 months iv. Head trauma with symptoms of increased intracranial pressure v. Hydrocephalus vi. Uncontrolled nausea (Greater than or equal to grade 3 despite 1 line of antiemetic), vomiting and headache (e.g. from cerebral metastases, trauma) vii. Greater than or equal to grade 3 despite one line of antiemetics • Factors of increased risk of sympathomimetic response (hypertension and tachycardia) with associated complications i. Uncontrolled hypertension with systolic blood pressure greater than or equal to 160 ii. Tachycardia with heart rate greater than or equal to 120 per minute. iii. Symptomatic ischaemic heart disease (e.g. exertional angina) and decompensated heart failure with NYHA class III and IV symptoms iv. Uncontrolled Hyperthyroidism (Low TSH with high T3 and/or T4) v. Diagnosis and history of Prophyria • Factors of increased risk of intraocular pressure with its complications i. Glaucoma ii. Open eye injury / Acute globe injury • Severe hepatic impairment: Bilirubin greater than or equal to 3 times upper limit of normal; AST and/or ALT > 5 times upper limit of normal - clinically determined to be due to hepatic impairment • Severe renal impairment (Creatinine clearance <15ml/min by Cockroft Gault Equation) • Other mental disorders apart from major depression (lifetime history schizophrenia/bipolar/mania) • Recent substance misuse as determined by the treating and research clinicians
Outcome results
None listed