Deborah Brauser

June 03, 2013

SAN FRANCISCO — Intravenous infusion of the N-methyl-D-aspartate (NMDA) antagonist ketamine may rapidly relieve symptoms of obsessive compulsive disorder (OCD), new research suggests.

A small proof-of-concept study of 15 adults with a moderate to severe form of the disorder showed a 50% responder rate for OCD symptoms 7 days after receiving a single intravenous (IV) infusion of ketamine and a 40% responder rate at the 2-week post-treatment point.

"We found a very fast decrease in OCD symptoms, but what's even more exciting is the sustained effects," lead author Carolyn Rodriguez, MD, PhD, assistant professor in the Department of Psychiatry at Columbia University College of Physicians and Surgeons in New York City, told Medscape Medical News.

"The bottom line is that ketamine can relieve symptoms in patients with constant intrusive thoughts. and the effect can persist in some OCD patients."

The results were presented here at the American Psychiatric Association's 2013 Annual Meeting.

Dr. Rodriguez noted that although this was a small study, it is an important first step.

"I think one of the things for clinicians to take away is that looking at medications in general that modulate glutamate may be of promise to our patients. Right now, ketamine is not at a stage to give to outpatients because it can have side effects," she said.

"Ketamine is really a nice tool to be able to look at mechanism of rapid effect and to be able to design better drugs."

Long Lag Time

"First-line [OCD] pharmacological treatments lead to limited symptom relief and typically have a lag time of 6 to 10 weeks before clinically meaningful improvement," write the investigators.

"Identifying pharmacological treatments with faster onset of action would be a major advance," they add.

Abnormalities in the glutamate system are thought to contribute to the pathology of OCD. Ketamine has previously been shown to modulate glutamate. Past studies have also shown that it offers rapid antidepressant effects.

Dr. Carolyn Rodriguez

"There has been a lot of excitement about glutamate as a neurotransmitter, so we decided to test ketamine IV infusion in a randomized design in individuals with OCD," said Dr. Rodriguez.

"I really feel like ketamine holds the key for teasing apart the differences in the neurobiology between OCD and depression," she added.

A total of 15 unmedicated adults (56% men; mean age, 34 years) with OCD but without comorbid moderate to severe depression were enrolled in this study. Their order of treatment was randomized.

Each participant received 1 intravenous infusion of ketamine 0.5mg/kg over 40 minutes followed by 1 infusion of saline (placebo) at least a week later — or received the 2 infusions in the opposite order.

All patients had a score of 16 or more at baseline on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS; mean score, 27.1) and a score of 25 or less at baseline on the 17-item Hamilton Depression Rating Scale (HDRS-17; mean score, 4.2). They also reported having intrusive obsessions for more than 8 hours each day.

The OCD visual analogue scale (OCD-VAS) was also administered.

Rapid Symptom Relief

Results showed that 50% of the participants reported significant improvement in obsessions, as measured by the OCD-VAS, 7 days after receiving the ketamine infusion, and 50% met criteria for treatment response (≥35% reduction in Y-BOCS score). None met criteria for treatment response after receiving the placebo.

For those who received ketamine first (so evaluations could be taken at both day 7 and day 14), the responder rate for OCD symptoms at day 14 was 40%.

Even though all participants had minimal depressive symptoms at baseline, their mean HDRS-17 score did decrease, although not significantly, after receiving ketamine (P = .058).

None of the patients dropped out of the study.

"These data suggest that ketamine can rapidly relieve symptoms of OCD, and this effect can persist for at least 1 week in...OCD patients with constant intrusive thoughts," write the investigators, adding that a subset of the individuals experienced relief of symptoms for up to 2 weeks.

"I think this study holds a lot of hope and promise for this line of research for our patients," added Dr. Rodriguez.

She reported that a larger study looking at these issues is now in the planning stages. "That is the next step and is in the works."

She also noted that other studies are currently being conducted on further ways to modulate the NMDA receptor. "What I think is nice about that line of research is that it has the promise of the rapid effects without the side effects that ketamine is associated with."

The study was supported by the National Institute of Mental Health and by grants from the Gray Matters Fellowship and Molberger Scholar Award. The study authors did not disclose any relevant financial relationships.

The American Psychiatric Association's 2013 Annual Meeting. Abstract NR4-01. Presented May 19, 2013.

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