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 (timetreatment condition: β = 0.8, [-1.6, 3.1]). Higher ACE scores were associated with greater symptom reduction (timeACE: β = -0.6, [-0.9, -0.3]), independent of treatment modality (timeACEtreatment 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 (timetreatment conditionage: 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 (timeACEage: 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.
Psychedelic Science