Ketamine and depression: a narrative review

Abstract

Depression is the third leading cause of disability in the world. Depressive symptoms may be reduced within several weeks after the start of conventional antidepressants, but treatment resistance concerns one-third of patients who fail to achieve recovery. Over the last 20 years, ketamine, an antagonist of the N-methyl-D-aspartate receptor, has been described to have antidepressant properties. A literature review was conducted through an exhaustive electronic search. It was restricted to Cochrane reviews, meta-analyses, and randomized controlled trials (RCTs) of ketamine for major depressive disorder and/or bipolar disorder. This review included two Cochrane reviews, 14 meta-analyses and 15 trials. Ketamine was studied versus placebo, versus other comparators and as an anesthetic adjuvant before electroconvulsive therapy. In 14 publications, ketamine provided a rapid antidepressant effect with a maximum efficacy reached at 24 hrs. Its effect lasted for 1–2 weeks after infusion, but a longer-term effect is little reported. Ketamine does not seem to improve depressive symptoms at the end of electroconvulsive sessions. Safety and tolerability profiles with ketamine at low single dose are generally good in depressed patients. However, there is a lack of data concerning ketamine with repeated administration at higher doses. The clinical use of ketamine is increasing. Intranasal (S)-ketamine has recently been approved for depression by the Food and Drug Administration. It could be a promising treatment in depressed patients with suicidal ideation. Collectively, the level of proof of efficacy remains low and more RCTs are needed to explore efficacy and safety issues of ketamine in depression.

Keywords:

• ketamine
• depression
• major depressive disorder
• bipolar depression
• suicide
• efficacy

Abbreviations

AMPAR, α-amino-3-hydroxy-5-méthylisoazol-4-propionate receptor; BDI, Beck Depression Inventory; BD, bipolar depression; BDNF, brain-derived neurotrophic factor; CSF, cerebrospinal fluid; DHNK, dehydronorketamine; ECT, therapy; GABA, gamma-aminobutyric acid; HDRS, Hamilton Depression Rating Scale; HNK, hydroxy-norketamine; HCN, hyperpolarization-activated cyclic nucleotide-gated; IV, intravenous; MDD, major depressive disorder; mTOR, mechanistic target of rapamycin; MADRS, Montgomery–Asberg Depression Rating Scale; NMDAR, N-methyl-D-aspartate receptor; RCT, randomized controlled trial.

Disclosure

The authors declare that there are no competing financial or non-financial interests in this work.