Effects of Ketamine in Treatment-Refractory Obsessive-Compulsive Disorder
Open accessAbstract
Background Treatments for obsessive-compulsive disorder (OCD) usually lead to incomplete symptom relief and take a long-time to reach full effect. Convergent evidence suggests that glutamate abnormalities contribute to the pathogenesis of OCD. Ketamine is a potent noncompetitive antagonist of the N-methyl-D-aspartate glutamate receptor. Trials have reported rapid antidepressant effects after low-dose ketamine infusion.Methods We conducted an open-label trial of ketamine (.5 mg/kg IV over 40 min) in 10 subjects with treatment-refractory OCD. Response was defined as >35% improvement in OCD symptoms and >50% improvement in depression symptoms from baseline at any time between 1 and 3 days after infusion.Results None of 10 subjects experienced a response in OCD symptoms in the first 3 days after ketamine. Four of seven patients with comorbid depression experienced an antidepressant response to ketamine in the first 3 days after infusion. Both OCD and depression symptoms demonstrated a statistically significant improvement in the first 3 days after infusion compared with baseline, but the OCD response was <12%. The percentage reduction in depressive symptoms in the first 3 days after ketamine infusion was significantly greater than the reduction in OCD symptoms.Conclusions Ketamine effects on OCD symptoms, in contrast to depressive symptoms, did not seem to persist or progress after the acute effects of ketamine had dissipated.
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An open-label ketamine trial of 10 participants found no effect on OCD symptoms.
“One open-label ketamine trial (n = 10) found that this agent had no effect on OCD symptoms”
From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [115]
The Methods and Results describe an open-label trial of 10 participants in which none met the predefined threshold for an OCD treatment response. But the Discussion reports an acute reduction in OCD symptoms and a modest improvement over the following days. The claim’s unqualified statement that ketamine had no effect on OCD symptoms overstates the finding. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn that trial, ketamine improved depressive symptoms in some participants.
“though it did improve depressive symptoms in some participants [115]”
From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [115]
Prior work has found that ketamine reduced OCD symptoms.
“Prior work has also found that ketamine reduced OCD symptoms (Bloch et al, 2012;Rodriguez et al, 2013).”
From Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial (2018) · cites this paper as Bloch et al, 2012
Ketamine effects on OCD symptoms, in contrast to depressive symptoms, did not seem to persist or progress after the acute effects of ketamine had dissipated.
“Ketamine effects on OCD symptoms, in contrast to depressive symptoms, did not seem to persist or progress after the acute effects of ketamine had dissipated”
From The neurobiological link between OCD and ADHD (2014) · cites this paper as Bloch et al. 2012
A negative outcome was reported in an open trial of ketamine in patients with OCD.
“while a negative outcome was reported in an open trial (Bloch et al., 2012).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Bloch et al., 2012
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- Authors
- Bloch, M. H., Wasylink, S., Landeros-Weisenberger, A., Panza, K. E., Billingslea, E., Leckman, J. F., Krystal, J. H., Bhagwagar, Z., Sanacora, G., & Pittenger, C.
- Affiliations
- Yale University (US)
- Yale New Haven Hospital (US)
- Corresponding author
- Bloch, Michael H.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 72
- Issue
- 11
- Pages
- 964-970
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3667652
- OpenAlex
- W2000519244
- Cited by
- 162
- References
- 45
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 19 · 2023: 13 · 2022: 9 · 2021: 13 · 2020: 7 · 2019: 5 · 2018: 13 · 2017: 15 · 2016: 12 · 2015: 16 · 2014: 11 · 2013: 8 · 2012: 1
- FWCI
- 13.05
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (K23MH091240, K08MH081190)
- National Center for Research Resources (UL1 RR024139)
- NIH (K23-MH077914)
- National Center for Research Resources to Yale University (UL1 RR024139)
- AstraZeneca
- Bristol-Myers-Squibb
- Hoffman La-Roche
- Merck & Compay
- Sunovion
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- ketamine, obsessive-compulsive disorder, treatment-refractory OCD, NMDA receptor antagonists, rapid antidepressant effects, comorbid depression, depressive symptoms, symptom persistence
- MeSH terms
- Adolescent, Adult, Antidepressive Agents, Depression, Female, Humans, Ketamine, Male, Middle Aged, Obsessive-Compulsive Disorder, Psychiatric Status Rating Scales, Treatment Outcome, Patient Selection, Excitatory Amino Acid Antagonists
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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