A Stanford psychiatrist is researching the effects of ketamine on the brains of patients with obsessive-compulsive disorder, hoping to determine why, in studies, the drug has provided relief from symptoms.
The first time psychiatrist Carolyn Rodriguez gave an infusion of ketamine to a patient with obsessive-compulsive disorder, she was nervous. After all, while ketamine is approved by the Federal Drug Administration as an anesthetic, it is also an illicit party drug known as “Special K,” with hallucinogenic effects and the potential for abuse.
“As a physician, you take an oath to do no harm,” said Rodriguez, MD, PhD, an assistant professor of psychiatry and behavioral sciences at the School of Medicine. “There are caveats with ketamine. People can feel disassociated, like they are floating; some feel nauseated.”
But the results simply astonished her.
The patient was a 24-year-old woman who had for years spent eight hours a day checking and rechecking that objects were precisely in place, due to her obsessions with symmetry and exactness. Midway through the 40-minute ketamine infusion, the patient said all obsessive thoughts and urges had suddenly disappeared.
“She was a lovely student who was very debilitated by her OCD,” said Rodriguez, who was an assistant professor at Columbia University at the time of this study of an individual patient, in 2009. “When I gave her the infusion, she was describing what she was feeling. About 20 minutes into the infusion, she just looked at me, eyes wide open, and said, ‘I feel like this weight has been lifted. Like I’m having a vacation from my OCD.’
“It was a very surreal moment. I thought, ‘Is she really saying that?’ I remember my heart was racing. I went back to my lab and said, ‘You will not believe this: It works.’”
Ketamine has brought fresh hope to a field desperate to find new treatments for hard-to-treat disorders such as severe OCD, a chronic condition marked by debilitating obsessions and repetitive behaviors. Current treatments, which include antidepressants such as Prozac, can take months to have any effect on the disease, if they work at all.
“Severe OCD takes such a toll on patients,” Rodriguez said. “The constant, intrusive thoughts that something is contaminated, the checking and rechecking, the repetitive behaviors. It interferes with your life, your jobs, your relationships.”
Severe OCD takes such a toll on patients.
Over the past 10 years, dozens of small studies have reported remarkable results in the use of ketamine to treat a variety of mood and anxiety disorders. Findings include the sudden alleviation of treatment-resistant depression, bipolar disorder and post-traumatic stress disorder. And these effects lasted days, sometimes weeks, after the hallucinogenic effects of the drug wore off.
Ketamine was developed in the 1960s and has been used for decades as an anesthetic during surgery. It can cause dissociative side effects — hallucinations and other psychotic-like symptoms — and has been used as a recreational drug. If used regularly, it can lead to dependence. It remains a mystery just how the drug works in the brain, and there are safety concerns about its current off-label use to treat patients. But researchers like Rodriguez are intrigued about the drug’s potential to help them identify a whole new line of medicines for fast-acting treatment of mental health disorders.
“What most excites me about ketamine is that it works in a different way than traditional antidepressants,” Rodriguez said. “Using ketamine, we hope to understand the neurobiology that could lead to safe, fast-acting treatments. I feel that is part of my mission as a physician and researcher.”
‘Right out of a movie’
Rodriguez’s interest in ketamine as a treatment for OCD was sparked about a decade ago when she was starting out as a research scientist at Columbia University. A small, placebo-controlled study published in 2006 by a mentor of hers, Carlos Zarate, MD, now chief of the section on neurobiology and treatment of mood disorders at the National Institute of Mental Health, had shown that ketamine induced dramatic improvement in treatment-resistant depression within two hours of infusion. It was a landmark study, drawing attention among the psychiatric community and launching a new field of research into the use of ketamine to treat various mood and anxiety disorders.
Stanford Medicine integrates research, medical education and health care at its three institutions – Stanford University School of Medicine, Stanford Health Care (formerly Stanford Hospital & Clinics), and Lucile Packard Children’s Hospital Stanford. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu.
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