Age-related moderation of adjunctive psychotherapy and early life stress effects on depression symptom reductions following ketamine treatment: Initial insights from a large, naturalistic sample.

Depression symptoms improved over time in patients receiving five ketamine infusions, with faster initial improvement that slowed later. Higher scores on the Adverse Childhood Experiences (ACE) survey were linked to greater symptom reduction, regardless of whether patients received ketamine-assisted therapy or infusions alone. Younger adults showed a stronger response to infusions alone compared to ketamine-assisted therapy, while older adults showed the opposite pattern. The association between higher ACE scores and greater symptom reduction was particularly pronounced in younger adults and reversed in older adults. These findings suggest ketamine may offer a targeted benefit for people with early life stress, especially younger adults.

Study at a glance

Abstract

Ketamine is known to be a rapid-acting antidepressant, but there is limited evidence regarding which types of patients are best-suited to this treatment and whether adjunctive psychotherapy improves outcomes. In a sample of 224 patients who received five ketamine infusions at a private clinic, this study uses Bayesian mixed modeling to examine the effects of early life stress (measured with the Adverse Childhood Experiences [ACE] survey) and treatment modality (ketamine-assisted therapy [KAT] vs. infusions only) on antidepressant response, and whether these effects interact. Depression symptoms were assessed prior to each infusion using the Patient Health Questionnaire-9 survey. Depression symptoms improved over time (time: β = -4.4, 95% Credible Interval [-6.8, -1.9]), with decelerating rates of improvement (quadratic time: β = 2.6, [0.4, 4.8]). Symptom trajectories did not differ between treatment modalities (time*treatment condition: β = 0.8, [-1.6, 3.1]). Higher ACE scores were associated with greater symptom reduction (time*ACE: β = -0.6, [-0.9, -0.3]), independent of treatment modality (time*ACE*treatment condition: β = -0.5, [-1.1, 0.2]). Exploratory analyses revealed that younger adults show greater treatment response to ketamine infusions alone compared to KAT, while the opposite is observed in older adults (time*treatment condition*age: β = -0.1, [-0.3, -0.03]). Furthermore, the relationship between higher ACE scores and greater symptom reduction may be particularly strong within younger adults, with this association reversing at older ages (time*ACE*age: β = 0.02, [0.002, 0.04]). In summary, enhanced magnitude of symptom reduction for those with greater early life stress exposure, especially in younger adults, suggests a potentially unique and targeted benefit of ketamine over conventional antidepressants for this population.