title: Effect of baseline anxious depression on initial and sustained antidepressant response to ketamine.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00088699.
authors.affiliation: Bldg 10, CRC Room 7-5545, 10 Center Drive, MSC 1282, Bethesda, MD 20892 dionescu@partners.org.
authors.forename: Dawn F
authors.initials: DF
authors.lastname: Ionescu
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Niciu
authors.forename: Erica M
authors.initials: EM
authors.lastname: Richards
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Slonena
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Vande Voort
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Brutsche
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
mesh_terms: D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000150:complications* / Q000188:drug therapy / Q000523:psychology; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine