Psychedelic Therapy: A Primer for Primary Care Clinicians – Part VII. Ketamine

Summary

Ketamine shows significant antidepressant effects, with a single intravenous infusion of 0.5 mg/kg reducing depression scores by an average effect size of d = 0.96 at 24 hours in a sample of 518 participants. It also effectively lowers PTSD symptoms and suicidal ideation compared to midazolam control. However, therapeutic benefits may diminish within weeks, necessitating repeated doses for sustained effects. Concerns include cognitive impacts, cardiovascular risks, liver toxicity, and bladder inflammation.

Study at a glance

Abstract

Background: Ketamine, an arylcyclohexylamine dissociative anesthetic agent, has evolved into a versatile therapeutic. It has a rapid onset, well-understood cardiovascular effects, and a favorable safety profile in clinical use. Its enantiomeric compound, esketamine, was approved by the FDA in 2019 for both treatment-resistant depression as well as major depressive disorder (MDD) with suicidal ideation (SI).Areas of Uncertainty: Research indicates dose-dependent impacts on cognition, particularly affecting episodic and working memory following both acute administration and chronic use, albeit temporarily for the former and potentially persistent for the latter. Alongside acute risks to cardiovascular health, ketamine use poses potential liver toxicity concerns, especially with prolonged or repeated exposure within short timeframes. The drug's association with 'ketamine cystitis,' characterized by bladder inflammation, adds to its profile of physiological risks. Therapeutic Advances: Data demonstrates a single intravenous (IV) infusion of ketamine exhibits antidepressant effects within hours (weighted effect size averages of depression scores (N=518) following a single 0.5 mg/kg infusion of ketamine is d = 0.96 at 24 hours). Ketamine is also effective at reducing PTSD symptom severity following repeated infusions (Clinician-Administered PTSD Scale [CAPS-5] scores: -11.88 points compared to midazolam control). Ketamine also decreased suicidal ideation in emergency settings (Scale for Suicidal Ideation (SSI) scores: -4.96 compared to midazolam control). Through its opioid-sparing effect, ketamine has revolutionized postoperative pain management by reducing analgesic consumption and enhancing recovery. Limitations: Many studies indicate that ketamine’s therapeutic effects subside within weeks. Repeated administrations, given multiple times per week, are often required to sustain decreases in suicidality and depressive symptoms.Conclusions: Ketamine’s comprehensive clinical profile, combined with its robust effects on depression, suicidal ideation, PTSD, chronic pain, and other psychiatric conditions, positions it as a substantial contender for transformative therapeutic application.