Depression

Lee et al. (2015) conducted a systematic review and quantitative meta-analysis on the use of ketamine as a potential treatment for major depressive disorder and bipolar depression. The results showed that ketamine significantly reduced depressive symptoms, with a large and statistically significant effect size observed at day 1. Moreover, these effects were sustained up to 7 days after infusion. These findings highlight the potential of ketamine as a promising new pharmacotherapy with rapid onset, high efficacy, and good tolerability for the treatment of depression.

 

McIntyre et al. (2021) published an international expert opinion paper on the use of ketamine and esketamine in treating treatment-resistant depression. Despite the proven effectiveness of traditional antidepressants, many individuals with major depressive disorder fail to fully recover with these treatments. Ketamine and esketamine offer new pharmacological approaches for adults with treatment-resistant depression and have shown rapid-onset efficacy, making them a promising option. However, concerns about safety and tolerability remain, and there is uncertainty about how to best implement these treatments in clinical practice. In their paper, the authors provide a synthesis of the available literature on the efficacy, safety, and tolerability of ketamine and esketamine for treating depression, and offer guidance on their implementation in clinical practice. The paper also discusses areas of consensus and future research directions.

 

A recent systematic review and meta-analysis by Marcantoni et al. (2022) examined the efficacy of intravenous ketamine infusion for treatment-resistant depression (TRD) from 2009 to 2019. The study analyzed 28 studies in 35 publications and found that a single ketamine infusion resulted in a strong effect within 4 hours, with maximum effect at 24 hours. The effectiveness of ketamine was still present 7 days post-infusion, with multiple infusions enhancing and prolonging the effect. The study provides support for the use of ketamine in rapidly managing depressive symptoms. However, more data is needed to understand the long-term safety and efficacy of ketamine use in patients with TRD.

 

Zarate et al. (2021) conducted a small randomized controlled trial to test the efficacy of ketamine in bipolar depression. The study found that within 40 minutes of administration, depressive symptoms and suicidal ideation significantly improved in subjects who received ketamine compared to those who received a placebo. This improvement remained significant up to Day 3, and 79% of subjects responded to ketamine while none responded to placebo. The study confirmed the previous finding that a single ketamine infusion could provide a rapid and strong antidepressant response in patients with bipolar depression. Additionally, the study showed that ketamine could rapidly improve suicidal ideation in these patients.

 

Two systematic reviews and a meta-analysis were conducted to evaluate the anti-suicidal effects of ketamine. Wilkinson et.al (2018) found in a review that a single dose of intravenous ketamine rapidly reduced suicidal ideation in depressed patients with suicidal ideation for up to 1 week, and its effects on suicidal ideation were partially independent of its effects on mood. The review by Hochschild's, Gruenbaum and Mann (2021) identified 11 RCTs that found an advantage for ketamine over control for rapid reduction in suicidal ideation in acutely depressed patients, with racemic ketamine being the most effective formulation. The review concludes that further research is needed to determine the optimal dosing strategy and long-term efficacy and safety. The meta-analysis of Xiong et al (2021) found that both intravenous racemic ketamine and intranasal esketamine were associated with robust reductions in suicidal thoughts at 2-h, 4-h, and 24-h post-intervention, suggesting the need for further research on the anti-suicidal efficacy of distinct formulations and routes of administration, including oral/sublingual ketamine and comparative studies.

​

See for more literature on Anxiety, Substance Abuse, Other Mental Health Conditions, Chronic Pain, Other Conditions.

​

Other useful articles

• Antidepressant Effects of Ketamine in Depressed Patients (2000)

• Efficacy of ketamine in the rapid treatment of major depressive disorder: a meta-analysis of randomized, double-blind, placebo-controlled studies (2016)

• Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories (2016)

• Ketamine Treatment for Depression: Opportunities for Clinical Innovation and Ethical Foresight (2017)

• The effect of ketamine on preventing postpartum depression (2020)

• Ketamine in Bipolar Disorder: A Review (2020)

• Ketamine for depression (2021)

• A qualitative study of patients’ experience of ketamine treatment for depression: The ‘Ketamine and me’ project (2021)

• Tolerance and acceptability of intravenous ketamine therapy for treatment resistant depression: a mixed methods assessment (2023)