Body Mass Index as a Moderator of Treatment Response to Ketamine for Major Depressive Disorder

Marlene P. Freeman, Rebecca S. Hock, George I. Papakostas, Heidi Judge, Cristina Cusin, Sanjay J. Mathew, Gerard Sanacora, Dan V. Iosifescu, Charles Debattista, Madhukar H. Trivedi, Maurizio Fava

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Purpose/Background Major depressive disorder (MDD) and obesity commonly co-occur. We sought to assess the impact of body mass index (BMI) on the acute antidepressant effects of ketamine in patients with treatment-resistant depression. Methods/Procedures Post hoc analyses were conducted from a multisite, randomized, double-blind, placebo-controlled trial designed to assess the rapid-onset effects of intravenous ketamine. Patients (n = 99) were randomized to a single dose administration of ketamine 0.1 mg/kg (n = 18), ketamine 0.2 mg/kg (n = 20), ketamine 0.5 mg/kg (n = 22), ketamine 1.0 mg/kg (n = 20), or active placebo, midazolam 0.045 mg/kg (n = 19). Patients were stratified for BMI. For patients randomized to ketamine (n = 80), BMI was assessed as a continuous variable and also categorically (obese, overweight, not obese/overweight [reference]). The primary outcome measure was the change on the 6-item Hamilton Depression Rating Scale 24 hours after treatment. Outcomes at day 3 were also assessed. Findings/Results The 6-item Hamilton Depression Rating Scale change scores at 24 hours were inversely associated with BMI (-0.28 ± 0.12, P = 0.02). With BMI operationalized categorically, both obese (-4.15 ± 1.41, P = 0.004) and overweight (-1.99 ± 1.14, P = 0.08) categories were inversely related to the 6-item Hamilton Depression Rating Scale change score at 24 hours, statistically significant for the obese category, as compared with the reference group. Similar but weaker findings were observed at 72 hours after infusion. Implications/Conclusions Higher BMI and obesity were associated with a more robust acute antidepressant response to ketamine. This may have clinical relevance for a great number of patients who have both MDD and obesity. Clinical Trial Registration: NCT01920555.

Original languageEnglish (US)
Pages (from-to)287-292
Number of pages6
JournalJournal of clinical psychopharmacology
Issue number3
StatePublished - May 1 2020


  • body mass index
  • depression
  • ketamine
  • obesity

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)


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