One-Third of Patients With MDD Benefit From Ketamine Therapy

The results of this replication study demonstrated similar response trajectories to those in previous studies.

One-third of patients with major depressive disorder (MDD) benefitted substantially from ketamine therapy, according to study results published in Journal of Affective Disorders.

Researchers sourced data for this study from a ketamine clinic in Chicago that was collected between 2018 and 2020. Patients (N=298) with MDD who had not responded to at least 2 prior lines of therapy and received 6 ketamine infusions at an initial dose of 0.50 mg/kg were evaluated for outcomes.

Patients had a mean age of 40.36 (SD, 14.11) years, 41.60% were women, mean Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) score was 16.61 (SD, 4.67), and mean Concise Health Risk Tracking Self-Report (CHRT-SR) score was 25.45 (SD, 10.00) at baseline. Childhood maltreatment was common in this cohort, with 34.20% reporting emotional abuse, 29.20% reporting physical neglect, 26.20% reporting emotional neglect, 24.20% reporting physical abuse, and 13.40% reporting sexual abuse. The mean Childhood Trauma Questionnaire-Short Form (CTQ-SF) score was 46.88 (SD, 18.20).

On the basis of treatment outcomes, a 3-class model best fit these data. Stratified by group, the largest (Moderate Depression Gradual Improvement [MD-GI]; 39.3%) comprised patients with moderate depression at baseline who had modest improvement from ketamine therapy. This was followed by the Severe Depression Rapid Improvement (SD-RI; 34.6%), which included patients with severe depression at baseline who improved substantially after undergoing ketamine therapy and Severe Depression Minimal Improvement (SD-MI; 26.2%), which included those with severe depression who did not benefit substantially from ketamine therapy.

[W]e confirmed distinct clinical trajectories of response to ketamine in depressed patients seeking treatment in the community.

At baseline, QIDS-SR scores were 20.28 points for SD-MI, 19.14 points for SD-RI, and 11.94 points for MD-GI. By visit 3, QIDS-SR scores were more similar between MD-GI and SD-RI groups. At week 6, SD-MI had the highest QIDS-SR score (mean, 17.76) and MD-GI (mean, 7.62) and SD-RI (mean, 6.98) scores remained at lower levels. Similar trends were observed for CHRT-SR scores.

The 3 groups differed significantly by gender, emotional abuse history, CTQ-SF scores, and CHRT-SR scores (all P ≤.030), in which more women, more who experienced emotional abuse, and patients with the highest CHRT-SR total and component scores were in SD-MI and the patients with the highest CTQ score were in SD-RI.

These findings may not be generalizable to patients who are unable to afford the cost of ketamine treatment, which can be $450-500 per infusion).

Study authors conclude, “In the present study we confirmed distinct clinical trajectories of response to ketamine in depressed patients seeking treatment in the community. Rapid and robust response to ketamine was not associated with relatively severe depression and self-reported childhood physical abuse. However, greater childhood maltreatment was associated with severely depressed patients seeking treatment, and more than half of these patients achieved a rapid and robust response to treatment.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


O’Brein B, Lee J, Kim S, et al. Replication of distinct trajectories of antidepressant response to intravenous ketamine. J Affect Disord. 2022;321:140-146. doi:10.1016/j.jad.2022.10.031