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Ketamine shows potential in anxious treatment-resistant depression

IV ketamine demonstrated similar efficacy in patients with anxious and nonanxious treatment-resistant depression, according to findings from a pilot study.

Though these exploratory results suggest that ketamine has potential for the treatment of patients with or without anxious treatment-resistant depression, future research is needed, according to researchers.

“Several controlled trials have now established the rapid and robust antidepressant effect of ketamine in patients with [treatment-resistant depression]. However, evidence for its efficacy in anxious depression remains scarce,” Naji C. Salloum, MD, from the department of psychiatry, Massachusetts General Hospital and Harvard Medical School, and colleagues, wrote in Depression & Anxiety.

Salloum and colleagues conducted secondary analyses of data from a recent randomized, active placebo-controlled trial of IV ketamine in patients with unipolar treatment-resistant depression that found response to ketamine-combined treatment was superior to midazolam. The researchers compared treatment response to ketamine vs. midazolam in patients with and without anxious depression.

In total, 99 participants with treatment-resistant depression were randomized to receive either a single dose of IV ketamine 0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, 1 mg/kg, or active placebo (midazolam 0.045 mg/kg). Researchers measured change on the Hamilton Rating Scale for Depression (HAMD-6), as well as change on the Montgomery–Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression-Severity scale (CGI-S). At 1- and 3-days post-treatment, they assessed the effect of anxious depression baseline status on response to ketamine compared with midazolam.

Overall, 45 patients had anxious treatment-resistant depression. Analysis revealed nonsignificant interaction effect between treatment group assignment (combined ketamine treatment groups vs. midazolam) and anxious/nonanxious status as measured by the HAMD-6 post-infusion on the first day (F = 0.02; P = .88) or the third (F = 0.12; P = .73). The investigators found similar results on the CGI-S and MADRS on both day 1 and day 3.

In addition, participants with anxious depression had a lower level of dissociative symptoms at 40 minutes after infusion initiation than those without anxious depression as measured by the Clinician-Administered Dissociative States Scale (M = 8.26 vs. 14.25; P = .04), according to the results.

“In contrast to reports from monoaminergic antidepressants, our data suggest that patients with anxious depression respond equally as well to ketamine compared to those with nonanxious depression,” Salloum and colleagues wrote. “The exact mechanism behind the differential response to ketamine versus other conventional antidepressants in anxious depression remains unclear. These results are still exploratory and future larger and adequately powered studies designed to specifically test this aim are warranted.” – by Savannah Demko

Disclosure: Salloum reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.