Effect of ketamine on anxiety: findings from the Ketamine for Adult Depression Study

Summary & key facts

In a randomized, double-blind trial in people with treatment-resistant depression, subcutaneous ketamine given twice weekly for 4 weeks lowered anxiety symptoms when higher, response-guided doses (0.5–0.9 mg/kg) were used. The lower fixed dose (0.5 mg/kg) did not show a clear benefit. The anxiety improvement seen with the higher doses was linked to improvements in overall depression scores and was not maintained 4 weeks after treatment stopped. The authors describe these analyses as exploratory and say the findings need confirmation.

Key facts:

• The trial (KADS) randomized 184 people with treatment-resistant depression; 174 participants received at least one study treatment and were included in the anxiety analyses.
• Participants were treated subcutaneously twice weekly for 4 weeks with either racemic ketamine or an active placebo (midazolam).
• Cohort 1 (fixed ketamine 0.5 mg/kg, n = 68) showed a non-significant change in Hamilton Anxiety (HAM-A) score: −1.4 (95% CI −8.6 to 3.2), P = 0.37.
• Cohort 2 (flexible, response-guided ketamine 0.5–0.9 mg/kg, n = 106) showed a statistically significant reduction in HAM-A score favoring ketamine: −4.0 (95% CI −10.6 to −1.9), P = 0.0058.
• MADRS inner-tension item (item 3) was significantly reduced in cohort 2 (P = 0.026) but not in cohort 1 (P = 0.96).
• The reported reduction in anxiety was mediated by change in total MADRS (overall depression) scores, suggesting the anxiety change was linked to antidepressant effects.
• Anxiety improvements were not maintained at the 4-week follow-up after treatment ended.
• The anxiety analyses were a secondary, exploratory part of the trial and were not corrected for multiple statistical comparisons; the authors state future studies are needed to confirm these findings.

Abstract

Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.

Topics

Functional Brain Connectivity Studies Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Anesthesia Anxiety Clinical psychology Depression (economics) Economics Ketamine Macroeconomics Medicine Psychiatry Psychology

Substances

Ketamine

Conditions & symptoms

Anxiety Depression Anxiety or worry Sadness or low mood