On the safety of repeated ketamine infusions for the treatment of depression: Effects of sex and developmental periods

Summary & key facts

This paper reviews what we know about using repeated low-dose ketamine infusions to treat people whose major depression did not get better after at least two antidepressant drugs. Many small studies show a single low-dose infusion can quickly reduce depressive symptoms and suicidal thoughts, usually for about one week. Giving repeated infusions can make the benefit last longer and be stronger, but the safety of repeated treatments is not well studied. Some clinical and animal reports raise concerns that repeated low doses might raise the risk of addiction and could harm thinking and memory, with possible differences between males and females and between teenagers and adults. More research is needed to know how safe repeated ketamine treatment really is.

Key facts:

• The paper is a review that looked at clinical and preclinical reports about repeated ketamine infusions for people with depression that did not respond to at least two antidepressant drugs.
• Many small clinical studies found that a single low-dose ketamine infusion can quickly reduce depressive symptoms and thoughts of suicide, and those effects usually last about one week.
• Repeated, intermittent ketamine infusions can prolong the antidepressant effect and often produce stronger benefits than a single infusion.
• The safety of repeated ketamine infusions has not been thoroughly studied, so we do not yet know the long-term risks.
• Some clinical reports and animal studies suggest repeated low doses of ketamine may have addictive properties, and female humans and adolescent females might be more sensitive to those addictive effects.
• Patients often report hallucinations, feeling disconnected from themselves, or other odd experiences during infusions, which raises concerns about possible lasting problems with thinking and memory after repeated treatments.
• Some reports indicate that men may be more sensitive to ketamine's psychosis-like effects, and animal studies found male rodents were more sensitive to ketamine-related changes in cognition at both adolescent and adult stages.

Abstract

In this review, we will discuss the safety of repeated treatments with ketamine for patients with treatment-resistant depression (TRD), a condition in which patients with major depression do not show any clinical improvements following treatments with at least two antidepressant drugs. We will discuss the effects of these treatments in both sexes at different developmental periods. Numerous small clinical studies have shown that a single, low-dose ketamine infusion can rapidly alleviate depressive symptoms and thoughts of suicidality in patients with TRD, and these effects can last for about one week. Interestingly, the antidepressant effects of ketamine can be prolonged with intermittent, repeated infusion regimens and produce more robust therapeutic effects when compared to a single infusion. The safety of such repeated treatments with ketamine has not been thoroughly investigated. Although more studies are needed, some clinical and preclinical reports indicated that repeated infusions of low doses of ketamine may have addictive properties, and suggested that adolescent and adult female subjects may be more sensitive to ketamine's addictive effects. Additionally, during ketamine infusions, many TRD patients report hallucinations and feelings of dissociation and depersonalization, and therefore the effects of repeated treatments of ketamine on cognition must be further examined. Some clinical reports indicated that, compared to women, men are more sensitive to the psychomimetic effects of ketamine. Preclinical studies extended these findings to both adolescent and adult male rodents and showed that male rodents at both developmental periods are more sensitive to ketamine's cognitive-altering effects. Accordingly, in this review we shall focus our discussion on the potential addictive and cognitive-impairing effects of repeated ketamine infusions in both sexes at two important developmental periods: adolescence and adulthood. Although more work about the safety of ketamine is warranted, we hope this review will bring some answers about the safety of treating TRD with repeated ketamine infusions.

Topics

Stress Responses and Cortisol Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Addiction Anesthesia Antidepressant Cognition Depression (economics) Dissociative Economics Hippocampus Internal medicine Ketamine Macroeconomics Medicine Pharmacology Psychiatry Psychology

Substances

Ketamine

Conditions & symptoms

Addiction Depression Addiction or harmful habbits Sadness or low mood