Anne Marie O'Melia, MS, MD, FAAP

Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of on open-label trial. Nir Lipsmann, Eileen Lam,  Matthew Volpini, Kalam Sutandar, Richelle Twose, Peter Giacobbe, Devin J. Sodums, Gwenn S. Smith, D. Blake Woodside, Andres M. Lozano. (2017). The Lancet Psychiatry, published online February 23, 2017. http://dx.doi.org/10.1016/S2215-0366(17)30076-7

Deep Brain Stimulation (DBS) involves the neurosurgical placement of electrodes attached to a stimulation device that delivers a current to a specific area of the brain. This report describes surgical intervention with DBS of the subcallosal cingulate in 16 patients with treatment refractory Anorexia Nervosa (AN) and reports on symptoms at follow up one year post intervention. For these patients, electrodes were placed into the subcallosal cingulate, an area of the brain that has been shown to have altered serotonin binding in patients with anorexia Nervosa. Subjects were all female, aged between 21 and 57 years old (mean of 34 years old). All treatment subjects were felt to be at risk of early death due to AN and all had failed to respond to multiple trials of conventional treatment. Prior to surgery, the patients had been suffering from AN for an average of 18 years. Minimum weight for study participants was set at a body mass index (BMI) of 13 kg/m2. The average of BMI at the time of surgery was 13.8). Most of the participants (14 of the 16) had a comorbid mood disorder, anxiety disorder or both.

The authors describe that the surgery and yearlong DBS had few serious adverse events. 14 of the 16 patients were still using their implanted stimulator one year after surgery. Depression symptoms had improved for 10 / 14 patients. Both depression and anxiety symptoms had improved for 5/ 14 patients. Quality of life measures were also significantly improved at one year follow up. Interestingly, psychological symptoms improved soon after the stimulation began while changes in weight lagged, starting for most participants after three months. This suggests that improving mental health may support weight gain. Over the course of the study, average BMI of the group increased to 17.3 kg/m2 and 6 out of 14 patients restored to a BMI of 18.5 or more. The authors propose that “limbic dysfunction might precede, and perhaps enable, later changes in weight”. When comparing PET scan results before treatment and after a year of stimulation, significant changes in glucose metabolism within and adjacent to the DBS target were found in key anatomical brain structures associated with AN.  This suggests that DBS directly affected brain circuitry in those areas. This included less brain activity in the putamen, thalamus, cerebellum and increased brain activity in the peripheral cortical areas (which are linked to social perception and behavior).

Why is this important?

In this study of severely nutritionally compromised patients, the safety and tolerability of the surgery and DBS were in line with previous studies of DBS in patients with depression and OCD. The treatment was safe, generally well tolerated and effective for most of the patients described. Anorexia Nervosa remains the psychiatric disorder with the highest mortality rate. It is a disorder with complex, multifactorial contributions. As we work to better understand the aberrant brain circuitry involved in causing and perpetuating the suffering of AN patients, it is important to advance the science of novel biologic approaches for treatment. This work shows how a multidisciplinary neuroscientific approach can lead to a new treatment. Although encouraging, we must await further study with larger, sham-stimulation trials before DBS finds a place in evidenced based treatment algorithms for Anorexia Nervosa.

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