Deep Brain Stimulation for the Treatment of Refractory Bipolar Disorder
Deep Brain Stimulation for the Treatment of Refractory Bipolar Disorder
Bipolar Disorder (BD) is among the most comon and challenging conditions in psychiatry.
 Although episodes of mania and hypomania define the different types of the disorder, the
 clinical picture is one dominated by depressed mood and agitation. The mainstay of BD
 treatment has thus far been pharmacologic, but many patients remain severely disabled by
 their condition, despite the best available medical treatment. The successful use of deep
 brain stimulation (DBS) in movement disorders, and its promising results in major depressive
 disorder (MDD), has led researchers to consider its use in highly selected refractory cases
 of BD. Evidence form the imaging and circuitry literature suggests that similar underlying
 dyfunctional anatomic structures subserve both MDD and BD, indicating that modulation of key
 structures, can lead to an amelioration of symptoms and mood stabilization. Here, we propose
 a phase I clinical trial to evaluate the safety of DBS in BD.
Bipolar disorder (BD) is a complex and disabling disorder that is among the most challenging
 diagnoses in psychiatry. Although episodes of mania and hypomania define the different types
 of the disorder, the clinical picture is one dominated by depressed mood and agitation.
 Detection and diagnosis of BD remains a challenge, as most individuals with BD spend many
 years misdiagnosed as major depression disorder (MDD), often leading to under-treatment or
 inappropriate treatment. Several studies have attempted to elucidate features of a major
 depressive episode that indicate an underlying diagnosis of MDD versus bipolar depression.

 During the last fifteen years, there have been significant advances in our understanding of
 the pathophysiology and relevant neuroanatomy and neurocircuitry underlying mood disorders.
 Much of that progress has been made as a result of technological advances in neuroimaging,
 both structural and functional.

 Deep Brain Stimulation is a neurosurgical tool has been used for over twenty-five years to
 treat various neurologic and psychiatric conditions. DBS is believed to work by using small
 amounts of electricity to disrupt the activity of brain structures that produce troublesome
 symptoms. In the case of Parkinson's disease, DBS is successful in treating the tremor and
 general slowing that are major parts of that condition. DBS has also been used in psychiatric
 patients, both as part of treatment, in cases of Obsessive-Compulsive Disorder (OCD), and
 research, in cases of Depression. The successful use of deep brain stimulation (DBS) in
 movement disorders, and its promising results in major depressive disorder (MDD), has led
 researchers to consider its use in highly selected refractory cases of BD. Evidence form the
 imaging and circuitry literature suggests that similar underlying dysfunctional anatomic
 structures subserve both MDD and BD, indicating that modulation of key structures, can lead
 to an amelioration of symptoms and mood stabilization.

 Our primary objective is to establish the safety of deep brain stimulation in a patient
 population with treatment refractory bipolar disorder.
Inclusion Criteria:

 -  Male or Female patients between the age of 30-60

 -  DSM IV-TR diagnosis of Bipolar Disorder I or II

 -  Diagnosis for >12 months with a HRSD-17 score of at least 20

 -  Failure of medical therapy, defined as follows:

 a. Failure of a minimum of two (2) first line as well as two (2) second line
 treatments for bipolar mania and depression

 -  No neurological disease

 -  No other active Axis I or Axis II co-morbidity that is the focus of clinical
 attention, as defined by the Mini International Neuropsychiatric Interview (MINI)

 -  No substance abuse or substance use disorder for minimum of three months prior to
 study

 -  Able to give informed consent

 -  Able to comply with all testing and follow-up visit requirements defined by the Study
 Protocol

 -  Mini mental status examination (MMSE) score >25

 -  Pre-menopausal women must agree to use acceptable methods of birth control (radiation
 risk of PET)

 Exclusion Criteria:

 -  History of psychosis, or psychotic episodes

 -  Alcohol or substance dependence or abuse within 6 months, excluding nicotine or
 caffeine.

 -  Current suicidal ideation, plan or intent for self-harm.

 -  A suicide attempt in the past 1 year

 -  Major medical illness, cardiac pacemaker/defibrillator, and other implanted stimulator

 -  Likely to relocate or move to a location distant from the study site within one year
 of enrollment

 -  Any contraindication to MRI or PET scanning