Carolyn Rodriguez Wins Prestigious Award for Innovative OCD Research

The most exciting clinical memory of Carolyn Rodriguez, M.D., Ph.D., was also one of her most nerve-wracking moments. Back in 2009, Rodriguez, then a postdoctoral research fellow, was finally ready to provide an infusion of ketamine to a patient with obsessive-compulsive disorder. Ketamine, an FDA-approved anesthetic (but also a party drug with the potential for abuse), was showing promise as a fast-acting antidepressant in some early clinical trials.

Rodriguez believed that ketamine could be equally effective at providing rapid OCD symptom relief. And after years of seeking funding and the necessary approvals, the last obstacle was that she didn’t have an anesthesiologist to perform the drug infusion, even after numerous inquiries to colleagues.

Donica Payne/DOE

“I literally walked through the anesthesiology department and started cold-knocking on people’s doors to ask if they wanted to help with my study,” she said. (Rodriguez did manage to find her specialist in Pamela Flood, M.D., who had experienced her own share of research challenges)

Once the first infusion was complete, though, Rodriguez felt all the obstacles and challenges were worth it. As the first participant (a young student obsessed with symmetry and exactness) received the ketamine, she described a rapid reduction in her obsessive thoughts. “Seeing her OCD symptoms vanish within hours was exhilarating - I had never before felt such a palpable sense of hope for patients,” Rodriguez recalls.

A decade later, Rodriguez, now an associate professor and associate chair of psychiatry and behavioral sciences at Stanford University School of Medicine and Vice Chair for APA’s Council on Research has continued her efforts to find rapid and reliable treatment for people with OCD and related problems like hoarding disorder. In addition to clinical studies, she employs advanced techniques in neuroscience to better understand how drugs like ketamine work.

Her innovative work has received many accolades, most recently with a Presidential Early Career Award for Scientists and Engineers (PECASE) in July. The PECASE recognizes investigators who are pursuing bold and innovative projects at the early stages of their careers and is considered one of the highest honors in scientific research.

Rodriguez, who is also a deputy editor of the American Journal of Psychiatry, says, “given the increasing pace of foundational science breakthroughs and technology advances, it is truly an exciting time to be doing mental health research.”

“I am especially grateful to have had the freedom to pursue high-risk, high-reward ideas early in my career with the support of the Brain & Behavior Research and Robert Wood Johnson foundations and private donors,” she said. “I can continue to work on the most challenging problems with the help of the International OCD Foundation and American Foundation for Suicide Prevention support, which provide opportunities for me and other scientists to generate critical pilot data that may fuel transformative change in the field.”

Rodriguez is also grateful to the altruism of clinical trial participants. “I am inspired by those who are willing to participate in a research study. We approach treatment development from the science and research sides, but we need partners who are experts in their own symptoms to understand whether these treatments work. Because of confidentiality, I can’t publicly thank these individuals who’ve donated their time, but I am very thankful for their participation.” Rodriguez also praised her parents, who many years ago decided to emigrate from Puerto Rico to Florida. They left behind a whole support network for the promise of greater educational opportunities for their two children.

The Path to OCD

Rodriguez made the most of that opportunity, developing an early fascination with science and the biological basis of human behavior. Driven by a desire to solve challenging problems, she enrolled in an M.D./Ph.D. program in medicine, health science technology, and neuroscience after completing her undergraduate degree at Harvard (with a major in computer science).

A clinical encounter with an OCD patient early in her residency at Columbia University solidified her passion for helping patients through both clinical and research pathways. “I was immediately struck not only by his private suffering, but also by all of the physical manifestations that made his life harder,” she said. “His distressing intrusive thoughts about contamination caused him to always wear gloves when he went outside. He washed his hands excessively. When he took his hands out of his gloves, they were red and raw. His pain made a big impression on me.” As she treated more individuals with OCD, Rodriguez was frustrated by the current first-line OCD treatments like antidepressants and cognitive-behavioral therapy, which take two to three months before symptoms are substantially reduced and often leave patients with residual symptoms. Rodriguez felt an urgent need for more effective and faster-acting treatments for OCD, which led her to look for new strategies like ketamine.

Following that first successful infusion, Rodriguez and her team led the first proof-of-concept clinical trial comparing low-dose intravenous ketamine with placebo in 15 OCD patients suffering from constant obsessions. Within one week after a single ketamine infusion, half the patients met the response criterion for OCD symptom reduction. The effect was rapid (within hours), and patients reported remarkable benefit. As with studies that have tested ketamine as an antidepressant, though, not every patient responded and several patients also experienced side effects like a feeling of disssociation.

Rodriguez has therefore spent the past several years working toward understanding the mechanism of ketamine’s rapid action and testing other compounds to see whether any might produce better symptom improvements with fewer side effects. Her lab is preparing to start a clinical trial testing hydroxynorketamine, a metabolic byproduct of ketamine that, in mice at least, can improve depressive-like symptoms without ketamine-like side effects.

In parallel, Rodriguez and a team of interdisciplinary colleagues are testing transcranial magnetic stimulation (TMS), a noninvasive treatment with the advantage of not having systemic side effects that many drugs have. In a significant milestone, TMS was recently cleared by the FDA last year for treatment-resistant OCD. However, as with medications, TMS for OCD takes time—approximately six weeks. However, recent technological advances in the way TMS pulses are delivered have dramatically shortened the duration of individual treatment sessions, and Rodriguez’s team is now pilot testing whether a 50% reduction in OCD symptoms can be achieved in five days.

Rodriguez is also interested in hoarding disorder, which was added as a distinct diagnostic entity from OCD in DSM-5. People with hoarding disorder put themselves at risk due to unsafe conditions in the home that can cause falls, fires, and pest infestation. Rodriguez is exploring the use of virtual reality as a means to help patients practice decision making, uncluttering, and tolerating the difficulty parting with possessions in a safe environment.

“Looking back, having strong mentors and sponsors who were willing to support me and encourage high-risk ideas—despite the challenges and skepticism—made the difference,” Rodriguez told Psychiatric News.  ■