Ketamine is a novel glutamatergic anesthetic agent, “repurposed” as a rapid-acting antidepressant for treatment-resistant depression (TRD). The enantiomer esketamine is now FDA approved, in conjunction with an oral antidepressant, for patients with TRD and major depressive disorder (MDD) with acute suicidal ideation or behavior. However, the evidence base is limited regarding the duration and efficacy of long-term ketamine use, with the risk of ketamine tachyphylaxis/tolerance. There are also large gaps in the literature regarding the long-term side effects of using ketamine on a maintenance basis.

Ketamine is considered a third line treatment with Level 3 evidence for acute bipolar depression. Thus, highlighting a potential role of ketamine in acutely treating bipolar depression. Multicenter intranasal esketamine trials excluded patients with bipolar depression, thus limiting the generalizability of esketamine MDD trials’ findings to bipolar depression. Ketamine clinics providing off-label ketamine infusions to patients have flourished throughout the United States, with many being run by prescribers with limited to no mental health experience.  Additionally, some of these clinics will treat a wide range of diagnoses including substance use disorder, at times with limited supervision.

This presentation will discuss the real-world efficacy and challenges of a ketamine clinic. This presentation will cover off-label use of IV ketamine and the FDA-approved esketamine for TRD, reviewing the evidence base synthesis of ketamine/esketamine in treatment-resistant unipolar and bipolar depression, clinical pearls, and efficacy and outcomes of long-term ketamine use.

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