The KINDRED Trial - Ketamine for relapse prevention in recurrent depressive disorder: a randomised controlled pilot trial
Ketamine is a competitive glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist with a remarkably rapid antidepressant effect, targeting core symptoms in treatment-resistant depression when given as single subanaesthetic doses (usually a 40 minute 0.5 mg/kg intravenous infusion).
The KINDRED study will be investigating if low doses of ketamine are better than a placebo drug at preventing relapse of depression after successful response to individual treatment (pharmacotherapy, psychotherapy and/or other multidisciplinary treatments). The study will also be investigating potential biomarkers associated with depression, including studies to evaluate selected peripheral blood neuroplasticity molecules. We will be exploring a sample of participants with a diagnosis of Major Depressive Disorder.
Trial registration and information for the KINDRED study can be found with the following EudraCT number: 2015-002020-37 or on ClinicalTrials.gov NCT02661061
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Depression is typically a recurrent disorder; over 50% of people who experience one depressive episode will have further episodes, whilst 80% of those who have had two episodes will experience a further depressive illness (APA DSM IV); with on average five to nine episodes in their lifetime. We reported in a recent meta-analysis that relapse rates following successful ECT are high: 27.1% after three months and 37.7% after six months. These rates are similar to patients who respond only after ≥3 antidepressant steps and most likely reflect the recurrent nature of treatment-resistant depression. We also found that, compared to placebo, taking antidepressants after ECT halved the risk (risk ratio=0.49, p<0.0001, NNT=3.3) for relapse at six months from nearly 80%. Some form of continuation therapy is therefore essential.
Ketamine is a competitive glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist with a remarkably rapid antidepressant effect, targeting core symptoms, in treatment-resistant depression when given as single subanaesthetic doses (usually a 40 minute 0.5 mg/kg intravenous infusion). Ketamine is psychotomimetic (with abuse potential) but at low dosage it’s safe, with patients and healthy controls experiencing mild dissociative and psychotic symptoms that resolve soon after finishing infusions. Repeated (e.g. 2-3/week for two weeks) infusions of subanaesthetic ketamine are safe with more sustained antidepressant effects.
These findings have led to the most exciting development in treating and understanding depression in over 50 years and represent a paradigm shift away from conventional slow-acting monaminergic antidepressants. An important potential use of ketamine is in prevention of relapse in people with depression.
Our upcoming research will focus on investigating the role of ketamine in relapse prevention; including studies to evaluate selected peripheral blood neuroplasticity molecules as biomarkers for depression and response to treatment.