David Baxter PhD
Late Founder
Deep Brain Stimulation Offers Hope for Severest Anorexia
by Caroline Cassels, Medscape
March 6, 2013
For the first time, deep brain stimulation (DBS) has been used to treat patients with severe, treatment-refractory anorexia nervosa (AN), with promising results.
The primary aim of the pilot study was to test the safety of DBS in this patient population. However, among the 6 patients included in the study, one half showed improvement in mood and body mass index (BMI) over baseline after undergoing the procedure.
According to investigators, these findings offer hope for patients with the severest form of AN, a chronic, highly resistant illness that carries significant mortality.
"DBS was associated in some patients with positive effects on BMI, mood, anxiety, and brain metabolism. Clinically, three of the six patients showed a change in the natural history of their disorder, achieving a sustained increase in BMI over a period of at least 3?6 months," the researchers, led by Andres M. Lozano, MD, Krembil Neuroscience Center and University Health Network in Canada, write.
The study was published online March 6 in the Lancet.
Deadliest of Eating Disorders
According to the study, AN has a mortality of 6% to 11% and is "among the most challenging psychiatric disorders to treat." It is also among the most common psychiatric disorders in young women aged 15 to 19 years.
A recent meta-analysis by investigators from the Eating Disorders Service in Leicester and Loughborough University, United Kingdom, showed that although all eating disorders carry a significant mortality rate, AN is the deadliest.
As reported by Medscape Medical News at that time, these study results showed that the death rate from AN was higher than the rates for either bulimia nervosa or eating disorder not otherwise specified. In addition, AN was linked to a very high rate of suicide.
Treatment typically focuses on behavioral change, but the investigators note that up to 20% of patients derive no benefit from available treatment and are at risk of dying prematurely from the disease.
Dr. Lozano and colleagues add that the "circuitry and biology of anorexia nervosa are areas of active investigation, with most disease models focused on structures that underlie pathological mood, anxiety, reward, body perception, and interoception."
They also point out that DBS has been used to treat other circuit-based neuropsychiatric diseases, including Parkinson's disease and major depression, with promising results.
Tested Target
To assess the safety of DBS in modulating the activity of limbic circuits and to examine its potential impact on clinical outcomes, the investigators conducted a phase 1, prospective trial of DBS in 6 patients with chronic, severe, treatment-refractory AN.
All patients were female, ranging in age from 24 and 57 years. The mean duration of illness was 18 years. Five patients had a history of acute recurrent hospital admissions for medical stabilization, and 4 patients had 10 or more admissions. Patients had a mean baseline BMI of 13.7
Participants underwent baseline depression, anxiety, and eating disorder assessments using the 17-item Hamilton Rating Scale for Depression, the Beck Depression Inventory),the Beck Anxiety Inventory, the Yale-Brown Obsessive Compulsive Scale, the Yale-Brown-Cornell Eating Disorder Scale in women, and the Quality of Life Scale. In addition, preoperative BMI was recorded for all patients.
The researchers used magnetic resonance imaging to identify the subcallosal cingulate, which was the chosen target for the procedure. The researchers note that subcallosal cingulate DBS has previously been shown to improve "symptoms in patients with treatment-refractory depression and reverses cerebral metabolic abnormalities in dysfunctional limbic circuits."
"With the evidence of shared symptoms and circuitry, we postulated that subcallosal cingulate DBS could also be helpful in anorexia nervosa," they write.
The procedure was performed under local anesthesia; 10 days after the surgery, patients returned to the hospital to have the device activated. Psychometric assessments were repeated at 1, 3, and 6 months after surgery. Weight was recorded, and BMI was calculated at 2, 3, 6, and 9 months after activation.
Patients also underwent neuroimaging preoperatively with 18F-fluorodeoxyglucose positron emission tomography (PET) and again after 6 months of continuous DBS.
Longest Sustained Weight Gain
Because it was a pilot study, the primary outcome measures were related to safety and included adverse events associated with surgery and those related to acute and chronic stimulation. Secondary outcomes related to weight, mood, and anxiety.
The investigators report that the surgery was generally well tolerated, with only 1 serious adverse event ? a seizure that occurred 2 weeks after the initial surgery and that was deemed to be the result of a metabolic disorder related to AN. The DBS stimulator was turned off in this patient and was reactivated 1 week later with no subsequent recurrence during follow-up.
"Although our experience is limited to six patients, the complication profile of DBS in this population can thus far be presumed to be low," the authors write.
In the weeks prior to surgery, 5 of the 6 patients had been attending inpatient treatment, which had resulted in some weight gain. As a result, the mean preoperative BMI was 16.1, "a value substantially higher than the typical baseline BMI for such patients."
Two months after surgery, all patients had lost weight, returning to their baseline, a finding that was in line with the investigators' expectations.
However, 3 months after the treatment, this pattern began to reverse itself, with 5 of the 6 patients stabilizing or gaining weight. After 9 months, 3 patients were maintaining a higher weight than before the treatment started; this was the "longest period of sustained increase in weight that any of them had achieved since the onset of their illness."
"Not Just Another Treatment"
At 9-month follow-up, the BMIs of the other 3 patients "were virtually unchanged from their historical baseline (within 0.3 points), which suggests that DBS had no apparent effect, positive or negative, on these patients' weights."
In addition, DBS was associated with improvements in mood, anxiety, affective regulation, and AN-related obsessive-compulsive behaviors in 4 patients and improved quality of life in 3 patients after 6 months of stimulation.
The investigators also note that a comparison of composite PET scans conducted at baseline and at 6 months revealed that these clinical effects were accompanied by "changes in cerebral glucose metabolism that were consistent with a reversal of the abnormalities seen in the anterior cingulate insula and parietal lobe in the disorder."
They add that the study's findings are "especially striking in view of the chronicity, severity, and life-threatening nature of the disorder in these patients, whose combined histories included almost 50 hospital admissions."
In an accompanying commentary, Janet Treasure, MD, PhD, and Ulrike Schmidt, MD, PhD, of King's College London Institute of Psychiatry, describe the study's findings as "promising," adding that the study "will give hope to patients with especially pernicious forms of [anorexia] and their families."
They also note that "the fact that the procedure was associated in some patients with improvements in affective and obsessional symptoms is of key importance, since such improvements will go some way towards reassuring patients that DBS is not just another treatment designed to fatten them up without making them feel better."
Dr. Lozano reports that he is a consultant for St. Jude Medical, Medtronic, and Boston Scientific and that he holds intellectual property related to brain stimulation for depression. The disclosures of the other authors can be found in the original article. Dr. Treasure and Dr. Schmidt report no relevant financial relationships.
Lancet. Published online March 6, 2013. Abstract, Commentary
by Caroline Cassels, Medscape
March 6, 2013
For the first time, deep brain stimulation (DBS) has been used to treat patients with severe, treatment-refractory anorexia nervosa (AN), with promising results.
The primary aim of the pilot study was to test the safety of DBS in this patient population. However, among the 6 patients included in the study, one half showed improvement in mood and body mass index (BMI) over baseline after undergoing the procedure.
According to investigators, these findings offer hope for patients with the severest form of AN, a chronic, highly resistant illness that carries significant mortality.
"DBS was associated in some patients with positive effects on BMI, mood, anxiety, and brain metabolism. Clinically, three of the six patients showed a change in the natural history of their disorder, achieving a sustained increase in BMI over a period of at least 3?6 months," the researchers, led by Andres M. Lozano, MD, Krembil Neuroscience Center and University Health Network in Canada, write.
The study was published online March 6 in the Lancet.
Deadliest of Eating Disorders
According to the study, AN has a mortality of 6% to 11% and is "among the most challenging psychiatric disorders to treat." It is also among the most common psychiatric disorders in young women aged 15 to 19 years.
A recent meta-analysis by investigators from the Eating Disorders Service in Leicester and Loughborough University, United Kingdom, showed that although all eating disorders carry a significant mortality rate, AN is the deadliest.
As reported by Medscape Medical News at that time, these study results showed that the death rate from AN was higher than the rates for either bulimia nervosa or eating disorder not otherwise specified. In addition, AN was linked to a very high rate of suicide.
Treatment typically focuses on behavioral change, but the investigators note that up to 20% of patients derive no benefit from available treatment and are at risk of dying prematurely from the disease.
Dr. Lozano and colleagues add that the "circuitry and biology of anorexia nervosa are areas of active investigation, with most disease models focused on structures that underlie pathological mood, anxiety, reward, body perception, and interoception."
They also point out that DBS has been used to treat other circuit-based neuropsychiatric diseases, including Parkinson's disease and major depression, with promising results.
Tested Target
To assess the safety of DBS in modulating the activity of limbic circuits and to examine its potential impact on clinical outcomes, the investigators conducted a phase 1, prospective trial of DBS in 6 patients with chronic, severe, treatment-refractory AN.
All patients were female, ranging in age from 24 and 57 years. The mean duration of illness was 18 years. Five patients had a history of acute recurrent hospital admissions for medical stabilization, and 4 patients had 10 or more admissions. Patients had a mean baseline BMI of 13.7
Participants underwent baseline depression, anxiety, and eating disorder assessments using the 17-item Hamilton Rating Scale for Depression, the Beck Depression Inventory),the Beck Anxiety Inventory, the Yale-Brown Obsessive Compulsive Scale, the Yale-Brown-Cornell Eating Disorder Scale in women, and the Quality of Life Scale. In addition, preoperative BMI was recorded for all patients.
The researchers used magnetic resonance imaging to identify the subcallosal cingulate, which was the chosen target for the procedure. The researchers note that subcallosal cingulate DBS has previously been shown to improve "symptoms in patients with treatment-refractory depression and reverses cerebral metabolic abnormalities in dysfunctional limbic circuits."
"With the evidence of shared symptoms and circuitry, we postulated that subcallosal cingulate DBS could also be helpful in anorexia nervosa," they write.
The procedure was performed under local anesthesia; 10 days after the surgery, patients returned to the hospital to have the device activated. Psychometric assessments were repeated at 1, 3, and 6 months after surgery. Weight was recorded, and BMI was calculated at 2, 3, 6, and 9 months after activation.
Patients also underwent neuroimaging preoperatively with 18F-fluorodeoxyglucose positron emission tomography (PET) and again after 6 months of continuous DBS.
Longest Sustained Weight Gain
Because it was a pilot study, the primary outcome measures were related to safety and included adverse events associated with surgery and those related to acute and chronic stimulation. Secondary outcomes related to weight, mood, and anxiety.
The investigators report that the surgery was generally well tolerated, with only 1 serious adverse event ? a seizure that occurred 2 weeks after the initial surgery and that was deemed to be the result of a metabolic disorder related to AN. The DBS stimulator was turned off in this patient and was reactivated 1 week later with no subsequent recurrence during follow-up.
"Although our experience is limited to six patients, the complication profile of DBS in this population can thus far be presumed to be low," the authors write.
In the weeks prior to surgery, 5 of the 6 patients had been attending inpatient treatment, which had resulted in some weight gain. As a result, the mean preoperative BMI was 16.1, "a value substantially higher than the typical baseline BMI for such patients."
Two months after surgery, all patients had lost weight, returning to their baseline, a finding that was in line with the investigators' expectations.
However, 3 months after the treatment, this pattern began to reverse itself, with 5 of the 6 patients stabilizing or gaining weight. After 9 months, 3 patients were maintaining a higher weight than before the treatment started; this was the "longest period of sustained increase in weight that any of them had achieved since the onset of their illness."
"Not Just Another Treatment"
At 9-month follow-up, the BMIs of the other 3 patients "were virtually unchanged from their historical baseline (within 0.3 points), which suggests that DBS had no apparent effect, positive or negative, on these patients' weights."
In addition, DBS was associated with improvements in mood, anxiety, affective regulation, and AN-related obsessive-compulsive behaviors in 4 patients and improved quality of life in 3 patients after 6 months of stimulation.
The investigators also note that a comparison of composite PET scans conducted at baseline and at 6 months revealed that these clinical effects were accompanied by "changes in cerebral glucose metabolism that were consistent with a reversal of the abnormalities seen in the anterior cingulate insula and parietal lobe in the disorder."
They add that the study's findings are "especially striking in view of the chronicity, severity, and life-threatening nature of the disorder in these patients, whose combined histories included almost 50 hospital admissions."
In an accompanying commentary, Janet Treasure, MD, PhD, and Ulrike Schmidt, MD, PhD, of King's College London Institute of Psychiatry, describe the study's findings as "promising," adding that the study "will give hope to patients with especially pernicious forms of [anorexia] and their families."
They also note that "the fact that the procedure was associated in some patients with improvements in affective and obsessional symptoms is of key importance, since such improvements will go some way towards reassuring patients that DBS is not just another treatment designed to fatten them up without making them feel better."
Dr. Lozano reports that he is a consultant for St. Jude Medical, Medtronic, and Boston Scientific and that he holds intellectual property related to brain stimulation for depression. The disclosures of the other authors can be found in the original article. Dr. Treasure and Dr. Schmidt report no relevant financial relationships.
Lancet. Published online March 6, 2013. Abstract, Commentary
