Higher BMI, Being Obese/Overweight Linked to Ketamine Response in MDD

Depressed fat man sitting on bed at home, worried about overweight, insecurities
In patients with major depressive disorder, higher body mass index and being obese/overweight were associated with a more robust acute antidepressant response to treatment with ketamine.

In patients with major depressive disorder (MDD), higher body mass index (BMI) and being obese/overweight were associated with a more robust acute antidepressant response to treatment with ketamine. Results of the study were published in the Journal of Clinical Psychopharmacology.

The investigators sought to evaluate the effect of BMI on the acute antidepressant effects of ketamine in patients with treatment-resistant depression. In this multisite, randomized, placebo-controlled, double-blind trial (ClinicalTrials.gov identifier: NCT01920555), male and female outpatients between 18 and 70 years of age were eligible for the study if they were experiencing an episode of major depression of ≥8 week’s duration and had received a diagnosis of MDD. All eligible participants were confirmed to have treatment-resistant depression during their current major depressive episode, which was defined as a failure to attain response (ie, ≥50% improvement) following ≥2 adequate treatment courses of antidepressant therapy. Post hoc analyses were performed in order to assess the rapid-onset effects of intravenous (IV) ketamine therapy in patients with MDD.

A total of 99 participants were randomized to receive a single-dose administration of IV ketamine 0.1 mg/kg (n=18), IV ketamine 0.2 mg/kg (n=20), IV ketamine 0.5 mg/kg (n=22), IV ketamine 1.0 mg/kg (n=20), or active placebo (midazolam) 0.045 mg/kg (n=19). All of the patients evaluated were stratified for BMI. Among the 80 participants who were randomized to ketamine, BMI was evaluated as a continuous variable and also categorically (ie, obese, overweight, or not obese/overweight).

Results of the study showed that the 6-item Hamilton Depression Rating Scale (HAM-D6) change scores at 24 hours were inversely associated with BMI (–0.28 ± 0.12; P =.02). When BMI was operationalized categorically, both the obese (–4.15 ± 1.41; P =.004) and the overweight (–1.99 ± 1.14; P =.08) categories were inversely linked to the HAM-D6 change scores at 24 hours, which was statistically significant (P <.05) for the obese group, compared with the reference group.

Limitations of the study include the single dose administration and inability to generalize to serial dosing of ketamine and to other modes of ketamine administration such as the intranasal, oral, or transdermal route.

The investigators concluded that the findings from the current study may have clinical relevance for a greater number of individuals with both MDD and obesity, provided the results are validated in longer-term studies of ketamine therapy.


Freeman MP, Hock RS, Papakostas GI, et al. Body mass index as a moderator of treatment response to ketamine for major depressive disorder. J Clin Psychopharmacol. 2020;40(3):287-292. doi: 10.1097/JCP.0000000000001209