None listed
Conditions
Brief summary
The co-existence of alcohol dependence and depression is common in clinical populations. The use of antidepressant drugs to treat depression is widespread however effects are modest and onset of effects are delayed. Availability of antidepressants with alternative pharmacological mechanisms, and potentially faster onset of action might be of particular benefit to this group of patients. One approach to developing novel antidepressants is via targeting the central glutamate system using Ketamine, a well established anaesthetic agent. Ketamine has the potential to rapidly alleviate depression and reduce alcohol consumption. This pilot study is to characterize the best use of ketamine for the rapid antidepressant treatment in depressed alcoholics. To date, most antidepressant data has been collected in patients without concomitant alcohol dependence, and therefore it is important to establish an appropriate dose-response and safety profile for ketamine in an alcohol-dependent population.
Interventions
The intervention is utilising ketamine at sub-anaesthetic doses. Dose range of ketamine is 0.1 to 2mgs/kg intramuscular (IM).
All subjects are scheduled to receive 4 separate infusions of blinded ketamine/saline placebo, with each administration separated by ~7 days. IM doses of ketamine in cohort 1 will be 0.1, 0.25 and 0.5mg/kg. In cohort 2, doses will be 0.5, 1, and 2 mg/kg (note: there is a common dose level between groups). Placebo will be inserted randomly into the dosing sequence. Clinic
The intervention is utilising ketamine at sub-anaesthetic doses. Dose range of ketamine is 0.1 to 2mgs/kg intramuscular (IM). All subjects are scheduled to receive 4 separate infusions of blinded ketamine/saline placebo, with each administration separated by ~7 days. IM doses of ketamine in cohort 1 will be 0.1, 0.25 and 0.5mg/kg. In cohort 2, doses will be 0.5, 1, and 2 mg/kg (note: there is a common dose level between groups). Placebo will be inserted randomly into the dosing sequence. Clinic visits for each subject are the ketamine dose procedure, Follow-up visits at day1, day 3 & day 7 post infusion (a total 4 visits per participant). For each participant there is an ascending dose subject to safety and tolerability of preceding dose. As above the 2nd cohort has a higher dose range.
Sponsors
University of Otago
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Diagnostic Statistical Manual - fourth edition, text revision (DSM-IV-TR) alcohol dependence; major depression with Montgomery-Asberg Depression Rating Scale (MADRS) scores >20 able and willing to give informed consent.
Exclusion criteria
Current chaotic multiple substance use (excluding alcohol, and tobacco — see medication below); currently in active moderate to severe alcohol withdrawal; actively suicidal or homicidal; pregnancy, nursing or refusal to use a reliable method of birth control in female subjects; severe psychiatric symptoms for which hospitalisation is being seriously considered; evidence of significant cerebral, renal, thyroid or cardiac disease; severe liver disease or liver failure. Medication: Disallowed medication: lamotrigine, memantine, amantadine, riluzole, N-acetylcysteine within 2 weeks; Monamine Oxidase Inhibitors (MAOIs) within 4 weeks; escalating doses of opioids.
Outcome results
None listed