Deep Brain Stimulation for the Treatment of Refractory Anorexia Nervosa
Condition: Anorexia Nervosa
MeSH terms: Anorexia; Anorexia Nervosa
Study type: Interventional

Summary: 
      Anorexia Nervosa (AN) is a challenging, chronic, refractory illness with the highest
      mortality rate of any psychiatric condition. Advances in the neuroimaging, genetics and
      neurobiology of AN has led to a greater understanding of its underlying pathophysiology,
      although few significant advances in treatment have been made in the last half-century. The
      central features of AN, which include an intense fear of gaining weight, a refusal to
      maintain a normal weight, as well as significant anxiety, anhedonia and dysphoria surrounding
      food, have been linked to dysfunction in key brain structures and circuits. Deep Brain
      Stimulation (DBS) is a neurosurgical procedure that involves the insertion of electrodes into
      structures believed to drive pathological behavior. The procedure is approved for the
      management of movement disorders, such as Parkinson's Disease, and has shown promising early
      results in the management of some psychiatric conditions, such as Major Depression. The
      purpose of this study is to explore the safety and initial efficacy of DBS, in patients with
      treatment resistant AN.
    

Detailed description: 
      Anorexia nervosa is a chronic, and debilitating psychiatric disorder associated with the
      highest mortality rate of any psychiatric condition. Despite advances in neuroimaging,
      genetics, pharmacology and psychosocial interventions in the last half century, little
      progress have been made in altering the natural history of the condition or its outcomes. It
      has further become increasingly accepted that the thoughts and behaviors at the root of AN
      derive from dysfunctional neuroanatomic circuits, whose activity and deviations can be
      detected with sophisticated neuroimaging techniques. Much progress has also been made in
      mapping the psychology of the illness to underlying neuroanatomic and neurophysiologic
      processes that drive and maintain these behaviors, even in the face of severe starvation and
      impending death. Dysfunctional reward processing, compulsive hyperactivity, chronic anxiety
      and depression, all suggest that AN shares much in common with other conditions, such as OCD,
      for which surgical therapy has been tried, and met with success.

      Deep Brain Stimulation is a neurosurgical tool that has been widely used for over twenty
      years. Most of the experience with DBS comes from the movement disorder literature where
      significant success has been had with the management of disabling Parkinson's disease (PD)
      and dystonia. The most experience so far has been in Parkinson's disease where well over
      50,000 patients globally have received the operation. DBS is believed to work by using small
      amounts of electricity to disrupt the activity of brain structures that produce troublesome
      symptoms. DBS has also been used in psychiatric patients, both as part of treatment and
      research, in cases of Obsessive-Compulsive Disorder (OCD), and research, in cases of
      Depression. Current research suggests that there are similarities between Anorexia Nervosa
      and conditions such as OCD and depression. Given that DBS has shown promise in the treatment
      of those conditions, this trial was designed to see if it could be an effective therapy for
      Anorexia Nervosa as well.

      This study would be the first exploration of a surgical therapy for refractory AN. The
      rationale stems from clear and robust evidence pointing at a dysfunctional
      cortical-subcortical loop driving abnormal behavior, with several important nodes in the loop
      being particularly important, and recurring, players. The subgenual cingulate plays a role in
      affective decision making, reward processing, as well as subsequent anxiety and dysphoric
      mood.

      There are currently no brain based, targeted therapies for AN. The scientific significance of
      this study will be:

      i) The first clinical trial exploring deep brain stimulation in an eating disorder population

      ii) The first demonstration of the influence of deep brain stimulation on dysfunctional
      reward processing with co-morbid anxiety/dysphoria

      iii) The first 'brain-based' treatment for any eating disorder
    

Intervention name(s): Deep Brain Stimulation
Intervention type(s): Device
Intervention description(s): Deep Brain Stimulation (DBS) is a neurosurgical procedure involving the implantation of deep brain electrodes, connected via a subcutaneous extension wire, to an implantable pulse generator (IPG, or 'battery') that is implanted below the collarbone.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment