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2023 HSR&D/QUERI National Conference Abstract

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1192 — Clinical Outcomes of IV Ketamine Treatment for Depression in VA

Lead/Presenter: Paul Pfeiffer,  COIN - Ann Arbor
All Authors: Pfeiffer PN (VA Center for Clinical Management Research, VA Ann Arbor Healthcare System, University of Michigan Medical School), Carty, J (Albuquerque VA Medical Center, University of New Mexico School of Medicine) Festin, Fe Erlita D. (VA Boston Healthcare System, Boston University School of Medicine) Ganoczy, D (VA Center for Clinical Management Research) Gilmer, WS (Edward Hines Jr VA Hospital, Northwestern University Feinberg School of Medicine) Martis, B (VA San Diego Healthcare System, University of California San Diego School of Medicine) Printz, D (VA San Diego Healthcare System, University of California San Diego School of Medicine) Rangathan, M (VA Connecticut Healthcare System, Yale School of Medicine) Wiechers, IR (VA Office of Mental Health and Suicide Prevention, University of California San Francisco School of Medicine) Hosanagar, A (VA Ann Arbor Healthcare System, University of Michigan Medical School)

Objectives:
Ketamine, an N-methyl-D-aspartate receptor antagonist, has novel antidepressant properties compared to commonly prescribed oral medications. Based on clinical trials, several VA medical centers provide IV ketamine for severe or treatment resistant depression, the latter of which occurs in an estimated 1/3rd of patients treated with oral antidepressants. To inform mental health services, we characterized patients who received IV ketamine for depression in VA, their response to treatment, and predictors of treatment response.

Methods:
We developed a keyword search algorithm (e.g., including the term “depression” in proximity to the term “ketamine”) to identify electronic medical record progress notes indicating IV ketamine treatment for depression in fiscal year 2020 (FY20). We validated algorithm-derived counts from each facility with their responses to a national survey of ketamine treatment for depression. Manual chart review was also used to verify infusions and to extract associated PHQ9 depression symptom scores when available. For each patient who received any IV ketamine treatment in FY20, we identified the date of their first infusion (including if it occurred in FY19) and extracted infusion outcome data for up to 12 months from the initial infusion date. Patient demographic characteristics, diagnoses, and mental health services use, including antidepressant treatments, were obtained from the corporate data warehouse.

Results:
IV ketamine patients (n = 220, 19 sites) in FY20 were 82% male, 14% over the age of 65 (mean age 50.1), 83% White, 4% Black, and 10% Hispanic. Frequency of diagnoses in addition to depression were: 19% bipolar disorders, 70% PTSD, 50% other anxiety disorders, 28% alcohol use disorder, 28% other substance use disorders, 12% personality disorders, and 79% pain disorders. In the year prior to their first infusion, patients attended a mean of 40 mental health visits, tried 2.0 antidepressant medications (5.9 different antidepressants in past 20 years), and 22% were psychiatrically hospitalized. Patients received a median of 16 ketamine infusions over 12 months with 96% receiving > 1 infusion. After 6 weeks of treatment, mean PHQ9 scores decreased from 17.4 to 14.0, with 47% of patients improving by at least 5 points, 25% responding with a 50% reduction in PHQ9 score, and 15% remitting with a PHQ9 score < = 5. Outcomes were similar at 12 and 26 weeks. In bivariate regression models, no demographic or baseline clinical characteristics predicted change in PHQ9 score from baseline to 6 weeks. The only statistically significant predictor was the number of infusions provided over that period, such that each additional infusion was associated with a 0.73 further decrease in PHQ9 score (p = .002).

Implications:
IV ketamine treatment for depression was rarely provided in the VA in FY20 relative to estimates of the prevalence of treatment-resistant depression. Improvements in symptoms outcomes were modest, but clinically relevant, considering patients had inadequate response to extensive prior treatment.

Impacts:
The VA should continue to support IV ketamine for treatment-resistant depression, and future research should seek to identify optimal treatment protocols, use of conjunctive medications and psychotherapy, and compare the clinical effectiveness of IV ketamine to other routes of ketamine administration and other alternatives to oral antidepressants.