New Treatments for OCD Show Promise
Dr. Carolyn Rodriguez spoke about novel treatments for obsessive compulsive disorder (OCD) that are in development, during a recent CC Grand Rounds lecture.
“I’m really excited for what’s on the horizon and have hope for the field,” said Rodriguez, associate dean at Stanford University and professor of psychiatry and behavioral sciences.
OCD is characterized by intrusive thoughts, images or urges that increase anxiety and compulsions (behaviors that can be mental or physical acts that decrease this anxiety).
OCD symptoms are present for 14 years, on average, before they are diagnosed and treated. “It can be a hidden disorder,” she explained. Obsessions often have certain themes, such as contamination and washing, symmetry and ordering, intrusive thoughts of harm, taboo thoughts and/or mental rituals.
Standard treatment for OCD includes selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy with exposure and response prevention. Patients typically begin taking SSRIs, which decrease the symptoms but don’t end them completely.
Behavioral therapy tries to disrupt the link between the anxiety-causing intrusive thought and the compulsion.
“Together, these two first-line treatments can help approximately half of individuals with OCD, but half of those individuals will not be helped,” Rodriguez noted. “That’s where the focus of my research is.”
Around the time she started her research, ketamine had been shown to relieve symptoms of depression within hours. Based on animal models of repetitive behaviors and emerging understanding of OCD, Rodriguez thought there was a mechanistic rationale to test the drug in OCD patients as well.
Ketamine is an FDA-approved anesthetic. Its side effects include hallucinations and out-of-body experiences, nausea and headaches. It’s best known as an illicit party drug because of its hallucinogenic effect.
Ketamine affects the brain’s glutamate system, which is involved in important brain functions such as learning and memory. Glutamate is the brain’s most common excitatory neurotransmitter. The drug blocks the NMDA receptor, which receives glutamate signals.
In a small pilot study, patients with OCD received a low dose of ketamine or saline via infusion. Those who received the ketamine reported a rapid decrease in OCD symptoms compared to those who received saline. One patient who received ketamine felt he had a vacation from his symptoms. Others reported they tried to have OCD thoughts but couldn’t.
“Those effects, amazingly, persisted past ketamine’s very rapid metabolism in the body,” Rodriguez noted.
In another study, she partnered with a team to study ketamine’s effect on brain activity in people with OCD. They wanted to determine whether ketamine changed levels of glutamate in an area of the brain called the prefrontal cortex.
Researchers gave patients a dose of ketamine and imaged their brains using magnetic resonance spectroscopy. After an hour, they didn’t see any changes in glutamate. They did, however, see elevated levels of an inhibitory neurotransmitter called Gamma-aminobutyric acid. It blocks chemical messages in the brain and decreases the stimulation of nerve cells.
“There may be a unique neurochemical signature in ketamine’s effects on OCD,” Rodriguez said. “This needs replication in a larger sample.”
Animal models suggest the drug increases activity in the frontal-striatal circuit, which is the part of the brain that controls compulsive grooming behavior. This circuit might be important in understanding ketamine’s therapeutic effects in OCD.
In addition, Rodriguez’s research has revealed ketamine’s antidepressive effects are tied to the brain’s opioid system. More research is needed to understand how the drug affects the opioid and glutamate system.
One hypothesis is that ketamine’s effect on the opioid system is responsible for the drug’s short-term depression relief, while the drug’s effect on the glutamate system is responsible for what makes the relief last a little while longer.
Rodriguez is also studying the potential of accelerated theta burst stimulation, a type of neuromodulation therapy. Neuromodulation refers to the alteration of nerve activity through electrical or chemical stimulation. Theta burst stimulation is a form of transcranial magnetic stimulation, a noninvasive treatment that uses magnetic fields to stimulate the brain.
To test whether accelerated theta burst stimulation could be a potential OCD treatment, she conducted an open-label study in seven patients. They received five consecutive days of accelerated stimulation. Ten sessions were applied per day (18,000 pulses/day, hourly) or 90,000 total pulses.
After the five-day protocol, her team saw patients experience a robust and rapid response in five of the seven (71%), with at least a 50% reduction in OCD symptoms within seven to 14 days.
“It was very dramatic,” Rodriguez said. Three patients sustained a reduction up to four weeks later. Some patients didn’t respond to the treatment. There were very few side effects (headache and fatigue that ended within a few days) from the treatment. More research is needed to understand why some patients respond and others don’t.
Rodriguez concluded, “There is a lot of pioneering research out there and a lot of hope,” both for patients who have been recently diagnosed with OCD and those who have struggled with it for a long time.