Journal
BIOLOGICAL PSYCHIATRY
Volume 72, Issue 11, Pages 964-970Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2012.05.028
Keywords
Clinical trial; glutamate; obsessive-compulsive disorder; major depressive disorder; ketamine; pharmacological therapy
Categories
Funding
- National Alliance for Research on Schizophrenia and Depression (NARSAD)
- American Psychiatric Institute for Research and Education (APIRE)/Eli Lilly Psychiatric Research Fellowship
- National Institutes of Health (NIH) [K23MH091240, K08MH081190]
- American Academy of Child and Adolescent Psychiatry (AACAP)/Eli Lilly Pilot Research Award
- Trichotillomania Learning Center National Center for Research Resources [UL1 RR024139]
- NIH [K23-MH077914]
- APIRE/Eli Lilly Psychiatric Research Fellowship
- AACAP/Eli Lilly Pilot Research Award
- Trichotillomania Learning Center
- NARSAD
- National Center for Research Resources [UL1 RR024139]
- Tourette Syndrome Association
- Talecris Biotherapeutics
- C8Sciences, Klingenstein Third Generation Foundation
- John Wiley and Sons, McGraw Hill, Oxford University Press
- NARSAD Young Investigator Award
- Clinical and Translational Science Award from the National Center for Research Resources to Yale University [UL1 RR024139]
- AstraZeneca
- Avanir
- Bristol-Myers-Squibb
- Evotec
- Eli Lilly Company
- Hoffman La-Roche
- Johnson Johnson
- Novartis
- Novum Pharmaceuticals
- Merck Compay
- Sunovion
- Pfizer Pharmaceuticals
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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 inOCDsymptoms 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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