Letter: Feasibility of Nucleus Accumbens Deep Brain Stimulation for Morbid, Treatment-Refractory Obesity (2017)

To the Editor: For the past 2 decades, deep brain stimulation (DBS) of the neurobehavioral network targets has been investigated for various conditions, including obsessive-compulsive disorder, major depression, addiction, and aggression. In 2011, we initiated an unblinded investigational use pilot study of DBS for the treatment of morbid obesity. This Letter to the Editor is intended to share insights gained from the 3 subjects enrolled and the challenges of that trial. The nucleus accumbens, ventral striatum, and ventral anterior internal capsule were the DBS target regions for this population due its role in the reward circuitry and behavioral self-regulation.1-4,7 Our approach for obesity specifically targeted the behavioral and addiction networks as compared to previous studies which investigated DBS of the hypothalamus.4-7 Our study was initiated after approval from the Food and Drug Administration (FDA; Investigation Device Exemption [IDE]) and Institutional Review Board in December 2011, “Deep Brain Stimulation for Morbid, Treatment-refractory Obesity.” Written informed consent was obtained from each individual prior to enrollment. We employed a sponsor investigator FDA-approved investigational use of a commercial product, which was intended to investigate the safety and feasibility of bilateral DBS of the nucleus accumbens and ventral anterior internal capsule for treatment of participants with intractable, treatment-refractory morbid obesity. Following review of the data from the first 3 subjects, our research group decided to discontinue the pilot study due to lack of feasibility. We present our insights to share with other groups who may wish to pursue DBS for obesity investigations. Briefly, our FDA IDE study inclusion criteria included adults aged 22 to 60 yr with “extreme obesity,” defined as body mass index (BMI) > 40, who had failed Rou-en-Y gastric bypass surgery. Participants were excluded if there was evidence of substance abuse or dependence, current severe major depressive disorder, active psychosis, or suicidality at screening as determined by the study psychologist. A total of 6 candidates (all female; age 50-55 yr) underwent screening and 3 were determined to be eligible for the pilot study. Despite having access to several hundred potential candidates from our Bariatric treatment clinics, we had difficulty recruiting for this study as evidenced by only 6 candidates being screened for eligibility and only 3 enrolling over a 3-yr period. This low recruitment may in part be due to patients not considering morbid and treatment-refractory obesity to be a neurological issue necessitating an invasive intervention to the brain. Obesity has traditionally been managed by diet, exercise, and, when extreme, bariatric surgery. DBS surgery was successfully completed in all 3 subjects and the correct placement of leads in the intended target was confirmed with postoperative imaging in all 3 subjects. Titration of the DBS and the determination of the chronic stimulation parameters were accomplished by a team of neurosurgeons and neurologists with extensive experience using DBS in this target region for depression, obsessive compulsive disorder, and traumatic brain injury. During the 3-yr study, participants were followed closely by a multidisciplinary team including psychologists with expertise treating bariatric surgery patients, neuropsychologists, dieticians, a regulatory expert, and a research ethicist, as well as neurosurgeons and neurologists with expertise in DBS. Although all 3 adult females who enrolled in the study lost weight with DBS, only 1 participant successfully completed the 3-yr trial, losing 100 pounds with a reduction in BMI from 55.7 at baseline to 39.3 kg/m2 at the last study visit. One subject withdrew from the study and requested explantation after 13 months in the study, and 1 patient died as a result of completed suicide after 27 months in the study. Given this, the investigative team deemed the feasibility of this line of research to be limited and decided to discontinue the pilot study and not to proceed with further enrollment in this trial. After a comprehensive and detailed review of the data for all 3 subjects, the study team concluded that DBS itself was not responsible for either the suicide or patient withdrawal and explantation. All 3 subjects had histories of significant psychiatric illness and were exposed to major psychosocial stressors during the trial such as family violence, estrangement/divorce, job loss, family illness, family death, pet death, and others. We believe these factors contributed to the events and lack of feasibility. In summary, despite evidence of weight loss with DBS in this study, the presence of significant psychiatric co-morbidity and ongoing exposure to psychosocial stressors presented major challenges to successful completion of the study. Future studies involving similar subjects should proceed with caution and incorporate strategies to mitigate this risk. Suggested strategies to consider include Requirement of close psychiatric monitoring by clinicians trained in bariatric psychiatry and mandatory psychological therapy during the study period. Requirement of subject commitment to compliance with the study requirements and close involvement with a social support system and a study partner (ie a family member or close friend committed to the trial with the subject) from the subject's environment. Upfront consideration should be given to the long-term follow-up of the DBS system after the trial conclusion and should be discussed with the subjects and family support system in advance of implantation. Morbid and treatment-refractory obesity is a significant public health problem, which deserves pursuit of all possible options to help these patients. It is associated with an increased risk of both health-related morbidity and a 3-fold increase in risk for mortality.8-9 Morbidly obese patients experience a higher prevalence of psychiatric disease–the most common being depression, anxiety disorders, and personality disorders–as well as increased risk of suicide.10-12 Bariatric surgery further increases the risk of suicide.9 The social stigma of obesity can affect a person's self-esteem, interpersonal relationships, education, and the quality of healthcare received.13-14 While we believe this treatment-resistant morbidly obese population could benefit from DBS, we caution other neurosurgical teams to pay close attention to study design, patient enrollment criteria, patient compliance, and patient monitoring. This is a high-risk and complicated population that requires a multidisciplinary team with expertise in neurosurgery, bariatric medicine, psychology, psychiatry, and social work to provide participants with comprehensive and frequent support and vigilance. Disclosures Funding was from the Neurological Research Institute, The Ohio State University. The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.