David S. Mathai, Madeleine Cluck, Amna M. Aslam, Erin Amato, Arsalan Azam, Michael Banov, Kathleen A. Barrett, Carl J. Bonnett, David Feifel, Nicolas Grundmann, H. Samuel Ko, R. McShane, Sandhya Prashad, Tatiana Santini, Lowan H. Stewart, Patrick Sullivan, Stefany D. Wolfsohn, Jill O. Robinson, Amy L. McGuire, L. Alison McInnes
BACKGROUND: Off-label use of intravenous ketamine (IVK) for depression is a widespread practice with limited regulation in the United States. There is an urgent need for current, evidence-informed treatment guidelines to facilitate patient safety, clinical decision-making, and care quality in real-world contexts. METHODS: The American Society of Ketamine Physicians, Psychotherapists and Practitioners (ASKP3) convened an interdisciplinary working committee tasked with creating guidelines for use of IVK for depression in outpatient settings. Guideline development followed a two-stage process: 1) a hybrid systematic and targeted evidence review and preliminary drafting by the committee, and 2) consensus refinement through a modified Delphi method using a panel composed of the committee and ASKP3 expert faculty. Panelists rated their agreement with proposed guideline items using a 9-point Likert scale, and consensus was predefined as a median rating ≥ 7 with an interquartile range ≤ 2 after Round 2. Consensus strength was evaluated using percentage agreement thresholds. RESULTS: Of 39 invited experts, 28 completed at least one round of the survey. Consensus was achieved on 73 of 75 of proposed guideline items (97%), with most items reaching very strong consensus (i.e., ≥90% of panelists rating a statement within the 7-9 range). Guideline items were organized across seven key practice areas. CONCLUSIONS: By combining a hybrid literature review and Delphi process, we developed expert consensus recommendations for the safe and effective use of IVK for depression. These guidelines can support decision-making, standardize clinical practice, improve patient outcomes, and promote equitable access to this emerging treatment, while informing ongoing research and policy development.