Item-Level Symptom Trajectories Across the PHQ-9 During At-Home Ketamine-Assisted Therapy for Depression: A Real-World Retrospective Analysis of 36,847 Adults

Background. The nine items of the Patient Health Questionnaire-9 (PHQ-9) index distinct symptom dimensions of major depressive disorder. Depression treatment is typically reported as change in the total score, so how individual symptom dimensions move during a rapid-acting treatment is seldom characterized. Ketamine is a rapid-acting glutamatergic antidepressant, but item-level trajectories during at-home, telehealth-supported ketamine-assisted therapy have not, to our knowledge, been described at this scale. Methods. We conducted a retrospective cohort analysis of 36,847 adults who initiated a new-client course of guided at-home sublingual or subcutaneous ketamine-assisted therapy for depression at Mindbloom, with a baseline PHQ-9 submitted between May 2021 and November 2025. For each PHQ-9 item, we analyzed the subset of patients elevated on that item at baseline (score of 2 or 3) and tracked change at three post-session timepoints (Post-Session 2, 4, and 6), computing within-subject change, percent reduction, paired Cohen's dz, the proportion improving by at least 1 point (response) and reaching 0 (resolution), and any worsening. The PHQ-9 total was analyzed among patients with at least moderate baseline depression (total ≥ 10), with response defined as a ≥ 50% reduction and remission as a total below 5. Results. Improvement was observed on every item, was measurable by the first post-session assessment (median 15 to 16 days), and strengthened through Post-Session 6. Post-Session 6 response rates (≥ 1-point improvement) ranged from 76.9% (sleep disturbance) to 94.9% (thoughts of being better off dead or of self-harm), with within-subject effect sizes from dz = 1.31 to 2.19, based on completer subsets of 175 to 1,769 patients per item. The largest percent reductions were on thoughts of being better off dead or of self-harm (73%), psychomotor change (71%), and negative self-evaluation (62%). Treatment-emergent ideation among patients with no or minimal baseline ideation was low, with emergence to a score of 2 or 3 in no more than 1.4% at any timepoint. The PHQ-9 total score declined 52% among Post-Session 6 completers (dz = 1.58), with 59.4% achieving a ≥ 50% reduction and 71.6% scoring below the moderate-depression threshold. Any patient-reported side effect was reported at 3.3% to 4.2% of post-session assessments and was not graded for severity or adjudicated for seriousness. Conclusions. In this large retrospective Mindbloom cohort, all nine PHQ-9 symptom dimensions improved during at-home ketamine-assisted therapy for depression, with early onset, progressive gains through six sessions, and large within-subject effect sizes. The findings are exploratory and hypothesis-generating, are consistent with a treatment effect, and would require controlled replication to confirm causality.