Ketamine treatment for refractory anxiety: A systematic review
Summary & key facts
This paper reviewed studies testing ketamine for people whose anxiety did not get better with usual treatments. It found that single doses of ketamine can reduce anxiety quickly and these effects can last as long as about a week after the main drug effects wear off. The review also says the anxiety relief looks temporary, the studies differ a lot in how ketamine was given and what other treatments were used, and scientists are not sure exactly how ketamine reduces anxiety in the brain.
- Ketamine has been shown in studies to lower anxiety quickly after a single dose.
- The calming effects of a single ketamine dose can last for up to about one week after the main psychoactive effects fade.
- Ketamine works at least partly by blocking a brain receptor called NMDA; that is linked to its pain and anaesthesia effects, but it is not clear how much this blocking explains the anxiety relief.
- The review calls the anxiety-reducing effects temporary, meaning they do not appear to be long-lasting without further treatment.
- There was a lot of mismatch across studies in important things such as how ketamine was given, whether patients had other treatments at the same time, and other study methods, which makes the evidence harder to compare.
- Because of the short duration of benefit and the wide differences between studies, the review suggests more consistent research is needed before firm conclusions can be drawn about ketamine as a regular treatment for hard-to-treat anxiety.
Abstract
There is a growing interest in the psychiatric properties of the dissociative anaesthetic ketamine, as single doses have been shown to have fast-acting mood-enhancing and anxiolytic effects, which persist for up to a week after the main psychoactive symptoms have diminished. Therefore, ketamine poses potential beneficial effects in patients with refractory anxiety disorders, where other conventional anxiolytics have been ineffective. Ketamine is a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor, which underlies its induction of pain relief and anaesthesia. However, the role of NMDA receptors in anxiety reduction is still relatively unknown. To fill this paucity in the literature, this systematic review assesses the evidence that ketamine significantly reduces refractory anxiety and discusses to what extent this may be mediated by NMDA receptor antagonism and other receptors. We highlight the temporary nature of the anxiolytic effects and discuss the high discrepancy among the study designs regarding many fundamental factors such as administration routes, complementary treatments and other treatments.