BEYOND MOOD: BROADER PSYCHOLOGICAL BENEFITS OF IV KETAMINE FOR MAJOR DEPRESSIVE DISORDER

Background

Intravenous ketamine has demonstrated efficacy in treating treatmentresistant depression (TRD), yet the accompanying psychological changes during treatment remain inadequately characterized.

Methods

We examined psychological measures in adults with treatment-resistant major depressive disorder receiving IV ketamine. Assessment instruments included the Adverse Childhood Experiences (ACE) questionnaire, Quick Inventory of Depressive Symptomatology Self-Rated 16-item (QIDS-SR16), Life Orientation Test-Revised (LOT-R), Brief Resilience Scale (BRS), Brief Resilient Coping Scale (BRCS), Cognitive Flexibility Scale (CFS), and Perceived Stress Scale (PSS). Participants were stratified into two cohorts: those completing baseline measures before initiating ketamine (pre-treatment), and those completing measures during ongoing treatment (mid-treatment). Follow-up assessments were administered at participants’ convenience. Treatment response was operationalized as ≥50% reduction in QIDSSR16 scores. Paired comparisons utilized Wilcoxon signed-rank tests. For the pre-treatment cohort, linear regression examined whether ACE scores predicted depression score changes, while logistic regression evaluated ACE effects on response rates.

Results

The combined cohort (n=27) had a median age of 52 years (22 females, 5 males). Among pre-treatment participants (n=12), 75% (9/12) achieved treatment response. Wilcoxon signed-rank testing demonstrated significant post-treatment reductions in QIDS-SR16 scores (median difference=11, 95% CI [7.5, 14.5], p=0.003). Significant improvements were observed in LOT-R scores (median difference=3.0, 95% CI [1.0, 5.0], p=0.02) and BRCS scores (median difference=4.0, 95% CI [1.0, 7.0], p=0.008). Changes in BRS (median difference=1.1, 95% CI [-0.2, 2.1], p=0.09) and CFS (median difference=8.4, 95% CI [-0.5, 18], p=0.06) approached but did not reach statistical significance. PSS scores decreased significantly (median difference=11.2, 95% CI [3.0, 20.0], p=0.02). In the mid-treatment cohort (n=15), none of the psychological measures (LOT-R, BRS, BRCS, CFS, PSS) showed significant changes. Median intervals between assessments were 7.2 months (pre-treatment) and 11.7 months (midtreatment). Neither linear nor logistic regression analyses revealed significant associations between ACE scores and treatment outcomes.

Conclusions

Patients initiating IV ketamine for treatment-resistant MDD demonstrated significant improvements in optimism, resilient coping capacity, and perceived stress levels. Near-significant trends emerged for cognitive flexibility and resilience. Conversely, patients receiving maintenance ketamine showed no significant psychological changes, suggesting no attenuation of initial treatment benefits during long-term therapy. Childhood adversity did not influence acute antidepressant response or remission rates. Study limitations include small sample size and exclusive use of self-report instruments.