Treatment-Resistant Depression (TRD) calls for the development of effective interventions for mood elevation and stabilization. Recently, both ketamine and its S-enantiomer (esketamine) have been investigated with successful clinical trials demonstrating effectiveness in TRD. More specifically, in 2019, intranasally administered esketamine, as opposed to the more effective intravenous ketamine, has been approved by the FDA as a treatment option for TRD. Treatment with esketamine, however, potentially comes with major adverse effects, including risk of psychosis, the possibility of abuse and dependence after repeated use, transient but non-negligible change in blood pressure and the heart rate, and potential toxicity on the urothelium and the liver. These risks are minimized when treatment is kept within the recommended dose range and the drug is administered by experienced medical personnel. Nevertheless, these risks appear to be offset by the effectiveness of esketamine in a wide range of depressive symptoms, such as anhedonia, anxiety, cognitive impairment, suicidality, and general dysfunction. This review highlights the need for more phase 4 clinical studies to evaluate esketamine’s performance in real life, including long-term effectiveness and risk studies.

ΚΕΥWORDS: Bipolar depression, ketamine, treatment resistant depression, effectiveness, adverse events.

Grigorios N. Karakatsoulis, Eva-Maria Tsapakis, Konstantinos N. Fountoulakis


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