Ketamine/esketamine pharmacotherapy for treatment of anxiety disorders and anxiety symptoms in depression: Systematic review.

Abstract

Ketamine and esketamine ("es/ketamine") treatment protocols have been investigated in patients' samples with treatment-refractory anxiety disorders. We systematically reviewed publications in which es/ketamine was used to treat anxiety symptoms in the context of either Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) anxiety disorders or treatment-resistant depression (TRD). The literature search of English-language studies combining each of the keywords "ketamine" or "esketamine" with various psychopathological terms produced 4086 results. Through the use of specific inclusion/exclusion criteria, a total of 78 studies were eligible for inclusion. Eleven studies investigated ketamine pharmacotherapy (no esketamine study was found) of patients suffering primarily from a DSM-5 anxiety disorder. Additionally, we found 67 studies which: (a) reported es/ketamine pharmacotherapy for treating primarily unipolar/bipolar depression and secondarily assessed changes in anxiety symptoms (N = 55); or (b) compared the outcome (depression/suicidality severity) of es/ketamine between "anxious" versus "non-anxious" TRD (N = 12). These studies were notably heterogeneous, and included randomized controlled trials, crossover trials, open-label studies, and case reports. Methods of administration of ketamine varied, including subcutaneous, intravenous, intramuscular, and oral; outcome measures also varied. Study findings suggest that es/ketamine is associated with a reduction of anxiety in the context either of anxiety disorders or of unipolar/bipolar TRD. These effects are sustained, especially with repeated doses and maintenance treatment: however, after terminating maintenance treatment anxiety symptoms may soon re-emerge. The tablet formulation reduces anxiety more slowly, but with fewer side effects. There are indications that es/ketamine pharmacotherapy may reduce pathological anxiety, although relapse may follow its termination. More studies are needed to confirm these preliminary findings.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

• State of the evidence: Esketamine for anxiety ↑Supports

  Across 78 heterogeneous studies, es/ketamine was associated with reduced anxiety in both anxiety disorders and treatment-resistant depression, with effects sustained especially with repeated or maintenance dosing, though anxiety may re-emerge soon after maintenance ends; no esketamine study was found for primary anxiety disorders.

  Synthesized October 23, 2026

Comparable studies

Other systematic reviews and meta-analyses on esketamine for anxiety, most cited first.