Reference Excerpt 8

Repeated oral ketamine for out-patient treatment of resistant depression: randomised, double-blind, placebo-controlled, proof-of-concept study.

(English) By: Domany Y; Bleich-Cohen M; Tarrasch R; Meidan R; Litvak-Lazar O; Stoppleman N; Schreiber S; Bloch M; Hendler T; Sharon H, The British Journal Of Psychiatry: The Journal Of Mental Science [Br J Psychiatry], ISSN: 1472-1465, 2019 Jan; Vol. 214 (1), pp. 20-26; Publisher: Royal College Of Psychiatrists; PMID: 30246667;

Background: Ketamine 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).

Method: In 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 ( 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).

Results: Twenty-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.

Conclusions: Repeated 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.