Ketamine May Be Equally Effective in Anxious vs Nonanxious Depression

Researchers found that there is a potential for the use of intravenous ketamine for anxious treatment-resistant depression.

Responses to ketamine may be similar in both anxious and non-anxious patients with treatment-resistant depression (TRD): This is unlike the patient responses typically seen with traditional antidepressants, according to a study published in Depression & Anxiety.

Researchers in this multisite, placebo-controlled, double-blind trial assessed the effect of a high baseline level of anxiety on the responses of patients with TRD to ketamine compared with midazolam (active placebo). Trial participants were randomly assigned to 1 of 5 treatment groups: a single intravenous dose of ketamine at 0.1, 0.2, 0.5, or 1.0 mg/kg or midazolam 0.045 mg/kg. The primary outcome was a change from baseline in the 6-item Hamilton Rating Scale for Depression (HAMD6). The effect of anxious depression at baseline (as defined by HAMD6 Anxiety-Somatization score ≥7) on post-infusion treatment responses at 1 and 3 days was examined using a linear mixed effects model.

Out of a total of 99 participants, 45 participants had anxious TRD at baseline vs 54 participants without high anxiety. Thirty-five patients in the ketamine group were high-anxiety participants compared with 10 in the midazolam group. When the combined ketamine treatment arms were compared with the midazolam active placebo arm, no statistically significant interaction effect was seen between anxious vs nonanxious status participants on day 1 (F [1, 84]=0.02, P =.88) or on day 3 (F [1, 82]=0.12, P =.73).

Study limitations include not assessing baseline anxiety status as a moderator of ketamine response compared with midazolam and the fact that separating ketamine into 4 groups resulted in a very small sample size. Also, without postbaseline HAMD-17 measurements, investigators could not determine if symptoms of anxiety improved as much as depressive symptoms did.

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Overall, investigators conclude that while these results could indicate that intravenous ketamine may be equally effective for the treatment of anxious and non-anxious TRD, the “results are still exploratory and future larger and adequately powered studies designed to specifically test this aim are warranted.”


Salloum NC, Fava M, Freeman MP, et al. Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression [published online December 30, 2018]. Depress Anxiety. doi: 10.1002/da.22875