Highlights:

• Strong evidence supports the rapid, although temporary, antidepressant effects of a single intravenous ketamine infusion for treatment-resistant major depressive disorder (MDD) and bipolar depression.
• Intravenous ketamine administration for treatment-resistant depression (TRD) is generally safe and well tolerated when administered by trained professionals.
• Ketamine research is transforming our understanding of the pathophysiology of mood disorders and leading the way toward developing new, rapid-acting interventions for TRD.

Conclusions:

Strong evidence supports the rapid, although temporary, antidepressant and antisuicidal effects of a single intravenous ketamine infusion for treatment-resistant MDD and bipolar depression. Continued investigation of ketamine via various routes of administration will continue to provide information about long-term safety and effectiveness for the treatment of depression. Given the growing use of intravenous ketamine and the potential approval of intranasal esketamine in the near future, evidence-based treatment recommendations for the use of ketamine in mood disorders need to be established.