The role of ketamine in the treatment of treatment-resistant bipolar depression
Grigorios N. Karakatsoulis, Eva-maria Tsapakis, Konstantinos Ν. Fountoulakis
Psychiatriki December 20, 2021 Peer reviewed DOI: 10.22365/jpsych.2021.052 via OpenAlex
Summary
Esketamine, an intranasal treatment for treatment-resistant depression (TRD), has shown effectiveness in alleviating various depressive symptoms despite potential major adverse effects like psychosis and abuse risk. It was approved by the FDA in 2019 but requires careful administration to minimize risks. The review emphasizes the necessity for further phase 4 clinical studies to assess esketamine's long-term effectiveness and safety in real-world settings.
Study at a glance
| Design | review |
|---|---|
| Key finding | Esketamine is effective for a range of depressive symptoms in TRD but carries significant risks that need to be managed. |
Abstract
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.