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

J Clin Psychopharmacol. May/Jun 2020;40(3):287-292. doi: 10.1097/JCP.0000000000001209.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Body Mass Index*
  • Depressive Disorder, Major / complications
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Treatment-Resistant / complications
  • Depressive Disorder, Treatment-Resistant / drug therapy
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Ketamine / therapeutic use*
  • Male
  • Middle Aged
  • Obesity / drug therapy
  • Overweight / complications
  • Overweight / drug therapy
  • Treatment Outcome
  • Young Adult


  • Ketamine

Associated data