Review of 78 studies on ketamine and esketamine for anxiety in anxiety disorders and depression

The question

Can ketamine or esketamine reduce anxiety, either in people diagnosed with an anxiety disorder or as anxiety occurring alongside depression?

What they did

Researchers searched the English-language literature for studies combining ketamine or esketamine with anxiety-related terms. The search returned 4086 records, and 78 studies met their inclusion criteria. Eleven of these looked at ketamine in people whose main diagnosis was a DSM-5 anxiety disorder. The other 67 involved treatment for unipolar or bipolar depression: 55 measured anxiety symptoms as a secondary outcome, and 12 compared results between “anxious” and “non-anxious” treatment-resistant depression.

What they found

No studies of esketamine in primary anxiety disorders were found — all 11 used ketamine. Across the included studies, the authors report that ketamine and esketamine were associated with reduced anxiety, both in anxiety disorders and in treatment-resistant depression. Benefits appeared to last longer with repeated doses and ongoing maintenance treatment, but anxiety symptoms could return soon after maintenance treatment stopped. The tablet form appeared to reduce anxiety more slowly but with fewer side effects.

The fine print

The included studies were highly varied in design (randomized trials, crossover trials, open-label studies and case reports), in how the drug was given (under the skin, intravenous, intramuscular or oral) and in which anxiety scales were used. In most studies anxiety was only a secondary measure, not the main target of treatment. Results were not pooled statistically, and the abstract does not report a total number of participants. This summary is based on the abstract alone.

What it means

There are early signals that ketamine may ease pathological anxiety, but the evidence is mixed in quality and anxiety may return once treatment ends; the authors themselves call the findings preliminary.

Evidence grade: Low. A systematic review that pools very mixed evidence — from randomized trials to open-label studies and case reports — without combining results statistically.

This summary is based on the study’s published abstract.