Conference Coverage

Ketamine may help OCD, but much work remains



– The recent Food and Drug Administration approval of intranasal esketamine for treatment-resistant depression has prompted interest in using this class of drugs in other conditions, including obsessive-compulsive disorder.

“OCD is severe, and one in seven people with OCD will attempt suicide in their lifetime,” said Carolyn Rodriguez, MD, PhD, associate professor of psychiatry and behavioral sciences at Stanford (Calif.) University.

Dr. Rodriguez presented some of her research on the mechanism of action of ketamine and its potential benefits for OCD during a session at the annual meeting of the American Psychiatric Association.

OCD patients experience a lengthy delay between treatment initiation and clinical benefit, sometimes 2 to 3 months, and most don’t achieve complete symptom remission, according to Dr. Rodriguez. “To help patients, I wanted to look at therapies that could be rapid acting, and given the converging lines of evidence that glutamate may play a role as an excitatory chemical messenger that helps neurons communicate, I looked at ketamine, which blocks the glutamate receptor,” she said.

A small study published in 2013 by her group was the first randomized, clinical trial of ketamine in OCD. It included 15 adults who experienced near-constant obsessions. A single dose given over 40 minutes led to a dramatic decrease in intrusive thoughts. One week after the infusion, four of eight patients who received ketamine met the criteria for a treatment response (35% or more reduction in Yale-Brown Obsessive Compulsive Scale scores), compared with none of the seven patients in the placebo group.

Dr. Rodriguez is now preparing to conduct a new trial comparing ketamine with midazolam as an active placebo, with the intent of looking at the drug’s effects on the circuits involved in OCD. “We need a large study to see if this is something that can be replicated, and we don’t know how long the effects persist. We’re just at the tip of the iceberg with OCD. In depression, there are these large studies that have been replicated, and in OCD, at least for randomized studies, it’s just this one study (from 2013) and the one that we have coming,” Dr. Rodriguez said.

Given the severity of OCD, ketamine and esketamine have generated some excitement, especially as a bridge to other therapies, such as cognitive-behavioral therapy or selective serotonin reuptake inhibitors.

The FDA’s approval of esketamine in March further boosted interest, but Dr. Rodriguez cautions that more research needs to be done. There is also at least one potential twist to use of an inhaled version of the drug. Contamination OCD patients may be unwilling to use a spray. In fact, Dr. Rodriguez’s team had to cancel a study looking at an inhaled form of racemic ketamine in OCD because they couldn’t recruit enough subjects. “There are variants [in OCD], and that’s why it’s important to study all populations and not assume that depression studies will cover the whole spectrum of our patients,” she said.

Dr. Rodriguez has consulted for Epiodyne, Allergan, BlackThorn, and Rugen.

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