Abstract of "Ketamine in Psychiatric Treatment: An Evidence‑Based Clinical Overview"
By Alexander Papp, MD, ABPN and Julie Myers, PsyD, MSCP | Point Loma Clinic, San Diego
Ketamine has undergone a remarkable transformation over the past two decades — from a dissociative anesthetic with a narrow clinical role to one of the most significant advances in the treatment of depression, suicidal ideation, and PTSD in a generation. This overview draws on current research, our clinical experience at Point Loma Clinic, and the emerging scientific consensus to offer a comprehensive account of what ketamine is, how it works, and what treatment actually looks like in practice.
We begin with the neuroscience. Ketamine's mechanism of action sets it apart from every conventional antidepressant: rather than acting on the serotonin or norepinephrine systems, it blocks NMDA receptors, triggering a cascade of downstream effects — rapid synaptogenesis, BDNF release, and normalization of dysfunctional brain networks — that produce antidepressant effects within hours rather than weeks. We cover the chemistry of ketamine's isomers and metabolites, its underappreciated interaction with the opioid system, and its effects on specific brain structures including the prefrontal cortex, hippocampus, amygdala, and lateral habenula.
On the clinical side, we address who is most likely to benefit — and who is not. The evidence is strongest for treatment-resistant depression, suicidal ideation, and PTSD, with emerging data for postpartum depression and other conditions. We are equally direct about the limitations: ketamine does not have strong evidence for chronic pain at standard doses, and certain medical and psychiatric contraindications require careful screening before treatment begins.
We describe in detail what ketamine treatment looks like at Point Loma Clinic: the intake evaluation, preparation, the initial six-session course, administration method, and how we monitor outcomes using validated instruments. A substantial section is devoted to the integration of psychotherapy with ketamine — including our Ketamine Coordinated Therapy approach — and to the range of subjective experiences patients report during sessions, from vivid perceptual journeys to sessions in which nothing unusual occurs at all, both of which can be therapeutically meaningful.
Finally, we address the broader landscape: the rapid and often poorly regulated growth of ketamine clinics, the serious risks of at-home ketamine use, the death of Matthew Perry as a cautionary case, and ketamine's place within the wider psychedelic renaissance in psychiatry. Our aim throughout is to give patients, referring clinicians, and the curious public an honest, evidence-grounded account of a treatment we believe, when administered carefully and within a full psychiatric context, represents a genuine advance in the care of some of the most difficult-to-treat conditions in mental health.