OCD patients with comorbidities respond well to deep brain stimulation

by CU Anschutz Medical Campus

Repetitive hand-washing is a common OCD symptom. Credit: Lars Klintwall Malmqvist/public domain

A new study published in Frontiers in Psychiatry finds that patients with Obsessive Compulsive Disorder (OCD) as well as other psychiatric comorbidities, such as autism spectrum or tic disorders, may respond well to Deep Brain Stimulation (DBS).

07 april 2021--DBS is a minimally invasive neurosurgical procedure that uses coordinates to target certain areas of the brain, implanting electrodes that can help regulate abnormal brain activity. DBS procedures are rare for OCD in the United States; only a couple hundred patients have received this treatment for OCD management since its FDA approval in 2009 via a Humanitarian Device Exemption. The effectiveness of DBS for OCD has been well-documented in literature, but the interplay with comorbid disorders has not been as thoroughly explored.

"This study helps us understand more about real-world use of DBS for OCD," says Rachel Davis, MD, associate professor in the CU Department of Psychiatry and study principal investigator. "Most patients seeking treatment don't only have OCD, comorbidities are more the rule than the exception. So it's important to understand how this life-changing procedure can benefit our more typical patients."

Davis and clinicians at the University of Colorado Anschutz Medical Campus retrospectively examined five patients seeking DBS for OCD between 2015 and 2019. Patients exhibited comorbidities including substance use disorder, eating disorder, autism spectrum disorder, major depression, ADHD, and tic disorder. Three patients were awake during DBS surgery, allowing clinicians to check for response to stimulation (improved mood, increased energy, and reduction in anxiety), an additional way to confirm correct electrode placement. After surgery, Davis assessed response and determined the correct settings by asking patients about changes in mood, energy, and anxiety. Improvement in these areas tend to be associated with reduction in OCD symptoms later on. Change over time was monitored with a variety of IRB-approved questionnaires, gauging changes in mood, anxiety, depression and other quality of life elements affected by OCD.

Overall, these patients experienced significant improvement in OCD and mood symptoms. A standard scale for assessing symptom severity and treatment response in OCD, the Yale-Brown Obsessive-Compulsive Scale (YBOCS), measures degree of distress and impairment caused by obsessions and compulsions. A good clinical response is considered to be greater than a 35% reduction. In this study, patients averaged a 44% reduction on this scale; four out of five experienced full response with the fifth having a partial response, with approximately 25% reduction in OCD symptoms. Patients also reported an average of 53% reduction in depression symptoms.

"For these treatment-refractory OCD patients, our Psychiatric DBS program, led by Dr. Davis, is finally providing relief," says John Thompson, Ph.D., associate professor of neurosurgery at the University of Colorado School of Medicine and one of the co-authors on this manuscript. "While DBS for OCD is rare, this study is a glimpse at its potential. There is much yet to be learned about the complex interplay between circuit modulation and co-morbid symptom management in OCD patients treated with DBS."

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More information: Lora Kahn et al, Deep Brain Stimulation for Obsessive-Compulsive Disorder: Real World Experience Post-FDA-Humanitarian Use Device Approval, Frontiers in Psychiatry (2021). DOI: 10.3389/fpsyt.2021.568932

Provided by CU Anschutz Medical Campus

TB Agent Helps in Obsessive-Compulsive Therapy

MINNEAPOLIS, July 20 -- For patients with obsessive-compulsive disorder, an anti-tuberculosis agent can jump start behavioral therapy, investigators here have found.
Patients given 125 mg of D-cycloserine (Seromycin), an N-methyl-D-aspartate (NMDA) partial receptor agonist, about two hours before an extinction-based exposure therapy session had significantly greater decreases in obsession-related stress after four sessions than placebo controls.
The D-cycloserine patients required fewer exposure sessions before they reached clinical milestones, and they had a much lower dropout rate than patients who took placebo, Matt Kushner, Ph.D., of the University of Minnesota, and colleagues, reported online in Biological Psychiatry.
"The dropout rate decreased dramatically," Dr. Kushner said. "Typically about 20 to 30% of people with OCD drop out of therapy. Only 7% of people who took the D-cycloserine dropped out."
In D-cylcoserine studies with rats, the drug accelerated extinction learning, speeding the loss of conditioned fear responses. In human studies, D-cycloserine has also been shown to improve responses to two sessions of exposure therapy in patients with social phobia, and four sessions in patients with acrophobia.
"Based on the earlier work," the authors wrote, "we predicted that D-cycloserine would also facilitate the capacity of exposure therapy to weaken the link between obsession-related stimuli (e.g., public restrooms) and feared outcomes (e.g., contamination), thereby reducing associated fear responding (e.g., distress) along with the need for rituals (e.g., washing) and avoidance."
The investigators randomly assigned patients with OCD to receive either placebo (17 patients) or D-cycloserine (15 patients) at 125 mg for 10 doses, to be taken about two hours before each session of cognitive behavioral therapy.
The patients had twice weekly sessions of cognitive behavioral therapy for five weeks, with standard exposure/ritual prevention therapy techniques applied by a trained psychologist.
Patients rated their 10-most disturbing stimuli on the 1-100 Subjective Unit of Distress Scale. The clinician then started working on the lower-rated stimuli first, and once a rating was decreased by at least 50%, a more challenging stimulus was tackled until all the ratings were cut by 50% of baseline, or until the 10th session was completed.
The authors found that the patients who received D-cycloserine had a more rapid decline in obsession-related fear rating through four exposure sessions, with the difference becoming significant at session four (t=2.3, P<0.05).
In addition, patients in the D-cycloserine group required an average of two fewer therapy sessions before reaching a greater than 50% decline in the distress scale ratings. At the end of their treatment sessions, however, there were no significant differences between the 14 remaining patients in the active drug group, or 11 patients in the placebo group.
"This offers another therapeutic approach where we can attempt to manipulate the memory process and the brain's reward/punishment system so people can learn healthier responses to various cues," Dr. Kushner said.
The investigators are currently exploring whether D-cycloserine might also help smokers abolish conditioned response to cues that trigger desire for a cigarette.
The authors acknowledged that the OCD study was limited by a lack of information on co-morbidities other than major depression or substance use disorder.
The work was supported in part by a grant to Dr. Kushner from the Obsessive-Compulsive Disorder Foundation. The journal did not provide authors conflict of interest information. Primary source: Biological PsychiatrySource reference: Kushner MG et al. "D-cycloserine Augmented Exposure Therapy for Obsessive-Complusive Disorder." Biol Pyschiatry 2007. doi:1-.1016/jbiopsych.2006.12.020