Ketamine works quickly, but doesn’t last, and some have a concerning adverse effect
STUDY: Eghdami S et al, Psychopharmacology 2026
STUDY TYPE: Systematic review
FUNDING: Iran University of Medical Sciences
Background
Glutamate pathways underlie many new approaches for OCD, like memantine, amantadine, n-acetylcysteine, and dextromethorphan. This review pulls together evidence on another glutamatergic, ketamine.
The Study
- 15 studies (3 randomized trials, 4 open-label trials, 8 case reports and series), 118 adults total with moderate to severe OCD
- Ketamine given intravenously, intramuscularly, orally, or intranasally, mostly at sub-anesthetic doses around 0.5 mg/kg
Results
Single-dose intravenous ketamine produced rapid response in 50 to 60 percent of patients in randomized trials, but the benefit from usually faded within a week.
Pairing ketamine with concurrent exposure and response prevention extended the benefit in smaller studies and case reports, with response sustained for weeks to over a year in some cases, suggesting that ketamine’s value may lie in opening a window for psychotherapy rather than treating OCD on its own.
Side Effects
Intranasal ketamine was poorly tolerated, with 75 percent of patients refusing it over contamination fears about the device (likely a problem for esketamine, Spravato, as well). Intravenous, intramuscular, and oral routes fared better. Dissociation was nearly universal but transient, resolving within one to two hours.
A Serious Risk
More concerning, a small subset of patients, particularly those with comorbid PTSD or a depression history, developed delayed-onset dysphoria and suicidal ideation 24 to 48 hours after infusion, a pattern distinct from ketamine’s reputation for easing suicidality in depression trials.
The finding is in line with other trauma studies. Although ketamine can be beneficial in PTSD, there are reports of worsened agitation, anxiety, and irritability in this population.
Practice Implications
- Ketamine is still experimental for OCD, and the new risk here raises questions about withdrawal phenomena in other populations.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
