Effect of baseline anxious depression on initial and sustained antidepressant response to ketamine

Patients with anxious depression are typically more difficult to treat with monoaminergic antidepressants compared to those with nonanxious depression. Although novel research has shown that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapidly acting, relatively sustained effects in treating depression, we predicted that, consistent with the existent literature on traditional antidepressants, patients with anxious depression would have a poorer antidepressant response.

Twenty-six inpatients with treatment-resistant major depressive disorder (MDD) (DSM-IV criteria) received a single infusion of ketamine (0.5 mg/kg over 40 minutes) from January 2006-March 2013 and were followed for 28 days. A post hoc analysis compared treatment response and relapse using the Montgomery-Asberg Depression Rating Scale (MADRS) in patients with anxious versus nonanxious depression. Anxious depression was defined as MDD plus a Hamilton Depression Rating Scale anxiety/somatization factor score ≥ 7.

Both anxious and nonanxious depressed patients responded positively to ketamine. A linear mixed model controlling for baseline with the MADRS revealed a significant group main effect (P = .03) and group-by-time interaction (P = .01). Post hoc tests indicated that patients with anxious depression had significantly fewer depression symptoms compared to those with nonanxious depression at days 1 through 5, 9 through 12, 15 through 17, and 25, with no significant group differences in dissociative (P = .62) or psychotic (P = .41) side effects. Regarding responders, patients with anxious depression relapsed significantly later than those with nonanxious depression (median ± SE = 19.0 ± 17.9 vs 1.0 ± 0.0 days to relapse, respectively; χ² = 9.30; P = .002).

Unexpectedly, patients with anxious depression responded better to ketamine than those with nonanxious depression, with longer time to relapse and no side effect differences. This finding gives promise for the role of novel glutamatergic medications for the treatment of those with anxious depression, a traditionally difficult-to-treat subgroup of depressed patients.

ClinicalTrials.gov identifier: NCT00088699.