Emerging Treatments for Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) affects an estimated 1% of the US population, and approximately 50% of cases are considered severe. Individuals with OCD have been reported to have significant functional disability and worse quality of life compared with those without the condition.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.

“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.5Additionally, 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 toldPsychiatry 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.

According to other findings, multiple cognitive enhancement strategies may also warrant further exploration in OCD treatment, such as: cognitive remediation therapy, which emphasizes the development of cognitive flexibility; the inference-based approach, a new approach for OCD with poor insight in which patients are taught to rely on momentary sensory information vs obsessive reasoning in order to more accurately assess reality; and habit reversal therapy, which helps to increase patients’ awareness of premonitory urges preceding compulsive actions and to engage in competing responses instead.4 “I think that OCD is a consequence of habit formation in many patients,” said psychiatrist Danielle Cath, MD, PhD, a psychology professor at Utrecht University in the Netherlands and one of the authors of the 2016 review. “Habits are lower-energy repetitions that tend to easily generalize, and they must be replaced by more goal-directed behaviors that cost more energy and require constant effort and attention in daily life,” she told Psychiatry Advisor.

When all other treatment options fail, more invasive techniques may prove to be appropriate. Findings show that ablative surgery could improve symptoms in 30% to 60% of patients with treatment-refractory OCD, and increasing evidence supports the relative safety and efficacy of deep brain stimulation, a less invasive approach that “functionally overrides and modulates pathological hyperactivity in disturbed networks, reducing the hyperconnectivity” of the cortico-striato-thalamo-cortical loops.4 Though deep brain stimulation has been associated with a 50% treatment response rate, researchers will need to elucidate “which characteristics of OCD patients determine which treatment option is the best,” said Dr Cath.

In some cases, the issues lie not with treatment efficacy but with clinician competency to appropriately deliver OCD-specific treatment. For example, though “medication is widely available, many professionals may not understand the most effective way to use these drugs, as it is different from how they are used for other disorders,” explained Dr Claiborne. The majority of patients require high doses over a period of 10 to 12 weeks in order to experience notable improvement, and some “experience exacerbation of symptoms early in a trial of SSRI medication, which may lead to discontinuation. This is unfortunate as this early increase in symptoms may predict a positive longer-term response,” he said.

As for CBT, patients are often unable to access a therapist adequately trained to treat OCD, which “requires very intensive treatments that we often do not offer, or they are suboptimally delivered,” according to Dr Cath. Providing effective treatment as early as possible may offer the best chance of recovery. Patients who remain partially symptomatic after treatment have an especially high risk of relapse in response to stressful life events, which becomes even more pronounced over time and with lower-impact events. “So there is a window of opportunity in first-onset OCD where we clinicians should do all we can to help patients become symptom-free,” she said.

Source: psychiatryadvisor.com

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