Oral ketamine for rapid reduction of suicidal ideation in major depressive disorder: A midazolam-controlled randomized clinical trial

Abstract

Background: The simplest, most convenient, and least expensive way to treat depressed and suicidal patients with ketamine is to administer racemic ketamine by the oral route. We describe the first active-controlled randomized clinical trial of oral racemic ketamine for suicidal ideation associated with depression.

Methods: Adult patients with major depressive disorder and expressed suicidal ideation were randomized to receive a single session of oral racemic ketamine (3 mg/kg; n = 40) or oral midazolam (0.3 mg/kg; n = 40). Suicidal ideation was rated using the Modified Scale for Suicidal Ideation (MSSI) and depression, using the 17-item Hamilton Rating Scale for Depression (HAM-D). Patients were assessed 4 h post-treatment (Day 1) and on Days 3 and 7.

Results: Mean doses were 180 mg and 1.8 mg for ketamine and midazolam, respectively. MSSI scores were significantly lower in the ketamine group at all assessment points: 4 h, Day 3, and Day 7. HAM-D scores were significantly lower in the ketamine group at 4 h and on Day 3. The study-defined HAM-D response and remission rates were 25 % vs 0 % and 5 % vs 0 % in ketamine vs midazolam groups on Day 7. Nausea/vomiting, lightness of body, emotional disturbance (anxiety or crying), and depersonalization/derealization were significantly more frequent in the ketamine group; however, no patient considered these to be of treatment-limiting severity.

Conclusions: Oral racemic ketamine is a reasonably well-tolerated and rapidly effective intervention for suicidal ideation and depression in adults with major depressive disorder.

Keywords: Adverse effects; Major depressive disorder; Midazolam; Oral ketamine; Randomized controlled trial; Suicidal ideation.