BackgroundKetamine has been demonstrated to improve depressive symptoms.AimsEvaluation of efficacy, safety and feasibility of repeated oral ketamine for out-patients with treatment-resistant depression (TRD).MethodIn a randomised, double-blind, placebo-controlled, proof-of-concept trial, 41 participants received either 1 mg/kg oral ketamine or placebo thrice weekly for 21 days (ClinicalTrials.gov Identifier: NCT02037503). Evaluation was performed at baseline, 40 and 240 min post administration and on days 3, 7, 14 and 21. The main outcome measure was change in Montgomery–Åsberg Depression Rating Scale (MADRS).ResultsTwenty-two participants were randomised to the ketamine group, and 19 to the control, with 82.5% (n = 33) completing the study. In the ketamine group, a decrease in depressive symptoms was evident at all time points, whereas in the control group a decrease was evident only 40 min post administration. The reduction in MADRS score on day 21 was 12.75 in the ketamine group versus 2.49 points with placebo (P < 0.001). Six participants in the ketamine group (27.3%) achieved remission compared with none of the controls (P < 0.05). The number needed to treat for remission was 3.7. Side-effects were mild and transient.ConclusionsRepeated oral ketamine produced rapid and persistent amelioration of depressive symptoms in out-patients with TRD, and was well tolerated. These results suggest that add-on oral ketamine may hold significant promise in the care of patients suffering from TRD in the community.Declaration of interestNone.

Background Depressed patients presenting to emergency departments with acute suicidal ideation are a major public health concern. Ketamine, a rapidly acting antidepressant with antisuicidal properties, might offer relief. Methods In a randomized, double‐blind, placebo‐controlled, proof‐of‐concept trial, 18 depressed subjects with acute suicidal ideation, who required hospitalization, were randomized to either an intravenous ketamine 0.2 mg/kg group or a saline placebo group. Safety and efficacy evaluations were scheduled for 15, 30, 60, 90, 120, 180, and 240 min, and on Days 1, 2, 3, 7, and 14 after infusion. The main outcome measure was suicidal ideation with secondary measures of depression. Results Nine subjects were randomized to each group. There were no differences between groups at baseline in any demographic or assessment scales. A reduction in suicidal ideation was noted at 90–180 min (p < .05). Ninety minutes after infusion, 88% of the ketamine group had achieved remission of suicidal ideation compared with 33% in the placebo group (p < .05). No serious adverse events were noted. Conclusions Ketamine was safe and effective for rapid reduction in suicidal ideation in depressed, highly suicidal subjects presenting to the emergency department. Our results support further study of ketamine for acute suicidal ideation.

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