Association of intravenous ketamine with change in depressive symptoms in a large integrated health care system.

Objective: Racemic ketamine intravenous treatments (KIT) are widely used in community clinics for treatment resistant depression (TRD), but we lack studies on symptom improvement during standardized delivery to clinically complex patients with TRD. We aimed to assess depression symptom change for patients receiving standardized KIT for TRD in a large integrated health care delivery system relative to similar patients receiving standard medication management.

Methods: In this retrospective cohort study (n = 570), depression symptom change measured by the 9-item Patient Health Questionnaire (PHQ-9) was examined in 143 adults with TRD receiving 0.5mg/kg 40-minute KIT infusion twice weekly for 3 weeks from 01/01/2018 to 12/31/2022 and 427 contemporaneous patients with medication management (MM) matched on variables including sex, race, age, and baseline depression symptom score. We excluded patients with major neurocognitive disorder, schizophrenia, or pregnancy.

Results: The KIT group was more likely to achieve depression response (PHQ-9 reduction >50 %) compared to MM (adjusted risk ratio [aRR]= 1.72, 95 % CI = 1.17 - 2.53; P = 0.006). The KIT group (8 % vs 5 %) was more likely to achieve depression remission (i.e. PHQ-9 < 5); however, the adjusted risk with KIT vs MM was not statistically significant. Baseline depression symptoms were associated with higher depression symptoms at follow up, as were co-occurring anxiety and personality disorders.

Conclusions: KIT was significantly associated with depression response and symptom improvement compared to MM. Clinicians should consider comorbid personality disorder, anxiety disorders, and baseline depression severity as potential predictors of KIT and other treatment response in TRD.