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

Summary & key facts

This paper is a review about how safe repeated ketamine infusions are for people whose major depression did not get better with at least two antidepressants. The authors say many small studies show a single low dose of ketamine can lift depression and suicidal thoughts quickly, but the benefit usually lasts only about one week. Giving ketamine in repeated, spaced-out infusions can make the improvement last longer and be stronger. However, the safety of repeating these infusions is not well studied. Some reports suggest repeated low doses might have addictive effects and might affect thinking, and that these risks could differ between males and females and between teens and adults. The authors call for more research before we can say how safe repeated ketamine treatment really is.

Key facts:

• The paper is a review that looks at what is known about repeated ketamine infusions for people with treatment-resistant depression, which means their depression did not improve after at least two antidepressant drugs.
• Many small clinical studies found that one low-dose ketamine infusion can reduce depressive symptoms and suicidal thoughts quickly, but those effects typically last about one week.
• Giving ketamine in several intermittent infusions can prolong the antidepressant effect and often gives a stronger benefit than a single infusion.
• The safety of repeated ketamine infusions has not been thoroughly studied, so we do not yet know the full risks of doing multiple treatments.
• Some clinical and animal reports suggest repeated low-dose ketamine might have addictive properties, and those reports suggest adolescent and adult females could be more sensitive to those addictive effects.
• Many patients report hallucinations and feelings of dissociation or depersonalization during ketamine infusions, so researchers say the effects of repeated treatments on thinking and memory need more study.
• Some clinical reports say men may be more sensitive than women to the 'psychomimetic' effects of ketamine, a term for drug-induced changes like hallucinations, and animal studies found male rodents showed more thinking-related changes after ketamine.

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 Addiction or harmful habbits