Rapid antidepressant effect of ketamine has been demonstrated in many recent studies . Five RCTs have shown that a single infusion is rapidly effective and the overall response rate at 72 hours was 29% compared to 7% with saline placebo . The response usually last hours to weeks and but most patients eventually relapse. A few extended trials have produced longer periods of antidepressant response.
The study by Diamond et al (Oxford) adds to this growing literature. This open label study was to explore the safety and efficacy of repeated infusions in patients who continued other psychotropic medications. They also looked at its effect on memory ( as this is a worry with ECT) and the feasibility of providing this treatment in routine ECT clinic settings.
Methods: Treatment resistant bipolar or unipolar depression were recruited. In the first stage patients were recruited to receive ketamine infusions once a week for three weeks. In the second stage a separate group was recruited to receive ketamine infusions twice a week for three weeks . The dose of ketamine administered was 0.5 mg/kg (ideal body weight) administered intravenously over 40 minutes. If a participant responded to ketamine and then relapsed after the final infusion they entered the maintenance phase of the trial.Participants were followed up for 6 months where possible.Primary measure of mood was the Beck Depression Inventory. Memory functions were assessed comprehensively using Autobiographical Memory Interview – Short Form (AMI-SF), Autobiographical Fluency Task, The Story Recall test (for episodic memory) and ECT Memory Questionnaire (for subjective memory).Antidepressant response was defined at a ≥50% reduction in BDI score from baseline to the end of the three week treatment on day 21, and remission as a score falling within the normal range (0–10) on the BDI. 44 patients were screened, of whom 28 were included in the analysis.
8/28 (29%) patients failed to complete all the planned infusions. (2 because of acute adverse reactions during the infusion, 5 because of failure to benefit and increasing anxiety and 1 for unrelated reasons). At day 21, 8/28 (29%, or 33% of completers) had reached response criteria. In all patients that met response criteria at day 21 a response had developed before the third infusion. At day 21, half of all responders met remission criteria. Majority of patients agreed that ECT clinic is the right setting to give the infusions. There were no memory defects associated with treatment.
Side effects: Infusions were not always well tolerated. one patient experienced a marked vasovagal episode lasting 10 minutes.Two patients experienced marked anxiety and two vomited during the infusions. Three of these four elected to continue the course but none were responders.Dissociative side-effects were common, but these were generally well tolerated.
Conclusion: In treatment resistant severe depression ( who are continuing with their antidepressants) 14% attained remission at day 21 with 29% reaching response criteria. All eventual responders showed this by third infusion.
Limitations: No control group, Open label study.
Comment: The response/ remission rate is very encouraging.Close monitoring is essential during and after treatment. The observation that by third infusion we could predict eventual response would aid in selecting this treatment as a trial. Results from the maintenance phase is not available now.
Summary of the article: Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic Peter R Diamond et al ahead of print.Journal of Psychopharmacology 1–9. 2014