Effects of ketamine in treatment-refractory obsessive-compulsive disorder.
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.
Yale Child Study Center, Yale University School of Medicine, New Haven, Connecticut, USA. michael.bloch@yale.edu
Michael H
MH
Bloch
Suzanne
S
Wasylink
Angeli
A
Landeros-Weisenberger
Kaitlyn E
KE
Panza
Eileen
E
Billingslea
James F
JF
Leckman
John H
JH
Krystal
Zubin
Z
Bhagwagar
Gerard
G
Sanacora
Christopher
C
Pittenger
D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D018579:Patient Selection; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine