Safety of brain implant for severe anorexia tested
The Independent has claimed that a "Brain pacemaker offers hope for anorexics".
The Independent’s story is based on a tiny pilot study on the safety of deep brain stimulation to treat severe anorexia. Deep brain stimulation involves giving continuous electrical stimulation to certain areas of the brain through surgically implanted electrodes.
Because this study aimed only to examine the safety of this very invasive treatment, it is a little early for the press to claim that deep brain stimulation ‘offers hope for anorexics’. Indeed, the researchers found that deep brain stimulation resulted, in one case, in a serious seizure, as well as several other adverse effects, such as pain and nausea.
On the other hand, since around one in five people with anorexia do not respond to conventional treatments, the fact that three of the six women in the study gained weight, and most reported improved mood and quality of life, gives reason for optimism.
Larger, more in-depth trials looking into the safety and effectiveness of deep brain stimulation would be needed before this treatment could be recommended as a standard treatment for anorexia.
Where did the story come from?
The study was carried out by researchers from the University of Toronto and York University, both in Canada, and Johns Hopkins University School of Medicine in the US. It was funded by a Canadian foundation for eating disorders research and the Canadian Institutes of Health Research.
The study was published in the peer-reviewed medical journal The Lancet.
The Independent’s claim that the treatment “offers hope” is premature given the early stage of the research. This claim could raise the hopes of families affected by anorexia without cause. The BBC News report helpfully includes comments from a patient in the trial and from independent experts.
What kind of research was this?
This was a phase one pilot study. It looked at the treatment of six patients with chronic severe anorexia, who had not responded to conventional treatment. This conventional treatment included a combination of therapy and medication.
The patients were treated with deep brain stimulation. This involves surgically placing electrodes in the brain. These then provide continuous electrical signals to specific parts of the brain.
Phase one trials are the earliest trials investigating a new treatment. They primarily aim to assess the safety of the treatment in a small number of people. Favourable phase one trial results mean that larger randomised controlled trials can be carried out to assess safety further, and to begin to look at the effectiveness of the treatment. Such trials of deep brain stimulation would include a control placebo treatment that might involve people having “sham” brain stimulation.
The researchers point out that anorexia – which they define as an eating disorder characterised by a refusal to maintain a healthy body weight and persistent fear of gaining weight – has a mortality of 6-11%. It is one of the most challenging psychiatric disorders to treat, not least because people with anorexia can be in denial about their condition. This means they are often unwilling to co-operate fully with their care.
Anorexia is associated with a complex interplay of perfectionism, anxiety and inability to control mood. Serious medical complications of anorexia include heart, musculoskeletal and neurological problems, and the most severe cases of the condition can prove fatal. Anorexia is one of the leading causes of mental-health-related deaths.
Current treatments focus on behavioural change and addressing underlying factors. People with anorexia may become very ill and need to spend time in hospital. Anorexia is usually a long-term condition and the researchers report that up to 20% of patients derive no benefit from current treatments.
The authors point out that current research on the brains of people with anorexia focuses on a region of the brain called the subcallosal cingulate. This region is known to be important in regulating mood.
The researchers say that deep brain stimulation has been used for more than 25 years to improve the activity of dysfunctional brain circuits and has proved effective and safe to treat people with Parkinson’s disease. Trials of deep brain stimulation for other conditions such as depression and Alzheimer’s are now underway.
What did the research involve?
Researchers included six women in their study. All were aged 20-60 years and they had all been formally diagnosed with anorexia nervosa for at least 10 years. To be included in the trial the women had to have failed to respond to repeated hospital admissions and treatment attempts for at least three years. The researchers ruled out any women with evidence of psychosis, neurological disorders such as epilepsy, or alcohol or substance abuse in the previous six months. Those with a BMI of less than 13 were ruled out, as were any who had conditions that made surgery a risk.
Participants were assessed at the start of the study using established symptom scales for:
- depression
- anxiety
- eating disorders
- quality of life
The women also underwent various brain scans.
Their BMI was recorded and baseline BMIs, based on their average BMI in the previous 5-7 years, were calculated.
Procedure to enable deep brain stimulation
The first part of the deep brain stimulation procedure involved implanting electrodes in the area of the brain associated with the regulation of mood. This procedure was performed under local anaesthetic and each electrode was stimulated at the time to check for spontaneous reports of mood or anxiety changes or adverse effects.
In the second part of the procedure, the electrodes were connected to a pulse generator implanted below the skin, just underneath the right collarbone, while the patients were under general anaesthetic. The devices were activated 10 days after discharge. Stimulation settings were changed on the basis of feedback from the patients and their doctors.
The patients had psychological assessments at one, three and six months after the devices were activated and further scans of the brain at six months. Weight was recorded and BMI calculated at two, three, six and nine months after activation of the deep brain stimulation devices.
The researchers looked at adverse events associated with the surgery and electrical stimulation, which were monitored at every visit. They also looked at BMI, and measures of mood and anxiety.
The brain scans before surgery and six months after surgery were also used to assess any changes in the brain’s glucose metabolism. Glucose metabolism is how the brain gets energy.
What were the results?
Deep brain stimulation was associated with several adverse events, including one serious adverse event in which a patient had a seizure (fit) roughly two weeks after surgery.
Other related adverse events that occurred around the time of surgery included:
- one patient had a panic attack during surgery
- one patient experienced nausea
- three patients experienced pain
- one patient had air embolus (a gas bubble formed in one of her heart blood vessels)
After six months, deep brain stimulation was associated with improvements in:
- mood, anxiety, regulation of mood and anorexia-related obsessions and compulsions in four patients
- quality of life in three patients
After nine months, three of the six patients had achieved and maintained a BMI greater than their baseline BMI, calculated as an average from the previous 5-7 years.
The way the brain metabolised glucose was also found to have changed after six months, compared with baseline.
How did the researchers interpret the results?
The researchers say the findings suggest that deep brain stimulation is generally safe in patients with chronic anorexia. They say their results also suggest that deep brain stimulation might be able to change the natural history of the illness, with the potential to improve clinical outcomes in some patients.
Conclusion
This was a small pilot study primarily set up to test the safety of deep brain stimulation in six people with severe anorexia. Studies of this kind are an essential first step in looking at whether a new treatment is safe.
Although the study has reported results relating to effectiveness, including changes in the patients’ BMIs or in their mood, a small pilot of this kind is not designed to look at effectiveness.
It is not possible to say whether any changes seen were due to the treatment or to other factors, such as a placebo effect from the treatment. They may simply be the result of the recognised fluctuations in weight and mood associated with anorexia.
This now needs to be followed by larger randomised controlled trials to look further at the safety of deep brain stimulation, and to begin to look at the effectiveness of this treatment for people with anorexia.
