Obsessive-compulsive disorder (OCD) affects an estimated 1% of the US population, and approximately 50% of cases are considered severe.1 Individuals with OCD have been reported to have significant functional disability and worse quality of life compared with those without the condition.2,3 First-line treatments — cognitive behavioral therapy (CBT) that includes exposure and response prevention, and selective serotonin reuptake inhibitors (SSRIs) — have been found to be effective for a portion of patients. However, previous findings show that partial remission occurs in approximately 40% of patients, of whom 60% experience relapse within 5 years of treatment. In addition, residual symptoms often continue to affect patients who do improve with treatment.4
“There are a number of reasons for the high nonresponse and relapse rates,” said clinical psychologist Jonathan S. Abramowitz, PhD, a professor and associate chair of the Psychology and Neuroscience Department at the University of North Carolina at Chapel Hill. The possibilities include “failure to engage in the treatment, presence of severe depression or psychotic symptoms, and very poor insight into the senselessness of the obsessions and rituals,” he told Psychiatry Advisor. Additionally, clinicians may not fully understand how to structure psychological or pharmacologic treatments to allow for optimal results.
There is a clear need for novel treatment options, and emerging evidence shows promise for several approaches. In the pharmacologic realm, a strong body of research indicates that SSRIs combined with clomipramine may improve short-term and long-term outcomes and reduce the risk of relapse.5 Additionally, consistent findings suggest that augmenting SSRIs with low doses of dopamine-blocking antipsychotic agents may improve outcomes for patients with treatment-resistant OCD. Studies have shown efficacy for several second-generation antipsychotics, including olanzapine, quetiapine, risperidone, and aripiprazole, with some data showing superior efficacy for risperidone in particular.4 A 2012 study concluded that “risperidone and aripiprazole can be used cautiously at a low dose as an augmentation agent in nonresponders to SSRIs and CBT but should be monitored at 4 weeks to determine efficacy.”6
Growing evidence also supports the potential efficacy of glutamate agents in treating OCD. “Research has suggested that glutamate is an important neurotransmitter implicated in OCD,” said James M. Claiborn, PhD, ABPP, a psychologist in private practice in Maine and a member of the Scientific and Clinical Advisory Board of the International Obsessive-Compulsive Foundation. “Glutamate-blocking drugs may be of value in augmenting SSRI medications or perhaps as monotherapy,” he told Psychiatry Advisor. While a 2012 open-label trial did not find support for the use of ketamine in improving OCD outcomes, a randomized trial reported in 2013 found that 50% of participants responded to treatment with a single dose of the drug.7,8 Results of several studies suggest that augmenting SSRI treatment with lamotrigine, memantine, or n-acetyl-cysteine may be effective for some patients.9
Various psychotherapeutic approaches have demonstrated treatment potential for OCD, including the use of d-cycloserine (DCS) along with CBT. DCS, “a partial agonist of the N-methyl-D-aspartate (NMDA) receptor, enhances the learning and memory processes underlying extinction of fear by indirectly stimulating the glycine recognition sites at NMDA receptors of the lateral and orbitofrontal cortex, dorsal anterior cingulate cortex, and insula,” wrote the authors of a review published in May 2016 in European Nueuropsychopharmacology.4 It is proposed that DCS might strengthen and expedite the extinction learning that exposure therapy appears to rely on.