Filling the Gap Between IV Ketamine Clinical Use and Evidence-Based Standards

Sandhya Prashad, MD, a board-certified psychiatrist specializing in interventional psychiatry and president of the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP3), discussed the rationale and methodology behind ASKP3's recently published interdisciplinary, Delphi-driven consensus guidelines for the use of intravenous (IV) ketamine in depressive disorders, and described the mechanistic basis of ketamine's antidepressant effects.

Prashad explained that IV racemic ketamine does not have approval by the US Food and Drug Administration for any psychiatric indication and is used exclusively off-label for depression, posttraumatic stress disorder, and related conditions. This regulatory status means there is no pharmaceutical sponsor to fund long-term safety and efficacy trials, no formal regulatory framework to capture outcomes data, and no established standard of care—despite approximately 15 to 16 years of routine outpatient use. Prashad argued that this gap between rapidly evolving clinical practice and the published evidence base made expert consensus methodology not only appropriate but necessary.

The Delphi process convened the ASKP3 expert faculty, consisting of a multidisciplinary panel including psychiatrists, anesthesiologists, emergency medicine physicians, and therapists, to rate 75 consensus items anonymously across iterative rounds. Consensus was achieved on 73 of the 75 items, resulting in what Prashad identified as the first formally Delphi-driven, interdisciplinary guidelines for IV ketamine in depression.¹ She noted a parallel effort by a separate, predominantly academic psychiatric group, distinguishing the ASKP3 guidelines by their broader multidisciplinary representation.

On mechanism, Prashad described ketamine's action as fundamentally distinct from that of conventional antidepressants. Ketamine blocks N-methyl-D-aspartate (NMDA) receptors, triggering downstream enhancement of neuroplasticity and rapid upregulation of brain-derived neurotrophic factor (BDNF)—which Prashad characterized as "fertilizer for neurons"—along with modulation of the default mode network.² She emphasized ketamine's well-documented rapid anti-suicidal effect as its most clinically significant property and attributed it in part to these rapid neuroplastic changes.

Dr Prashad is a board-certified psychiatrist specializing in interventional psychiatry and president of the American Society of Ketamine Physicians, Psychotherapists, and Practitioners.

References

1. McInnes LA, Aslam AM, Prashad S, et al. Interdisciplinary, Delphi-driven consensus guidelines on the use of intravenous ketamine infusions for depressive disorders from the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP3). J Affect Disord. 2026;411:121970.

2. Duman RS, Li N. A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists. Philos Trans R Soc Lond B Biol Sci. 2012;367(1601):2475–2484