rTMS for Treatment of Depressed Phase of Bipolar Disorder Type II

This is a double-blind randomized controlled trial of rTMS for outpatients in the depressive
phase of BD-II. Participants will be evaluated at UT Southwestern Medical Center at Dallas.
Forty eligible subjects will be randomized to either active treatment (n=20) or sham (no
stimulation, n=20). Each subject will receive treatment 5 days per week for a total of 6
weeks. At the end of the 6 weeks, those who remain depressed will have the option of
receiving 6 additional weeks of open rTMS treatment. We require these participants to meet
the same eligibility criteria in the open phase (i.e. MADRS ≥15, YMRS <12) as in the initial
double blind phase. At the completion of treatment, a follow-up appointment will be
scheduled with a study physician to ensure that the participant is properly transitioning to
clinical care and is not having a significant change in clinical status. Those who do not
already have a treating physician will be referred to a new provider.

Inclusion Criteria:

- Male and female outpatients aged 18-55 years old

- Meet DSM-IV criteria for Bipolar Affective Disorder Type II, depressed phase without
psychosis as determined by Structured Clinical Interview for DSM-IV

- A MADRS ≥ 15 at Initial Visit, and at Prior to TMS Evaluation

- A Young Mania Rating Scale < 12 at Initial Visit and at Prior to TMS Evaluation

- Duration of current episode of depression >2 months but ≤ 1 year of unsuccessful
treatment

- On stable medication and/or psychotherapy for 1 month and clinically appropriate to
maintain for duration of trial

- Cognitively intact (Folstein MMSE score >24).

- Clinically competent to give informed written consent

Exclusion Criteria:

- History of epilepsy or seizure disorder, mass brain lesions, cerebrovascular
accident, metal in the skull, a history of major head trauma, or any neurologic
condition likely to increase risk of rTMS.

- Suicidal risk that precludes safe participation defined as score of 5 or 6 on MADRS
item 10 Suicidal Thoughts or clinical impression that the subject is at significant
risk for suicide.

- History of any DSM-IV Axis I diagnosis other than Bipolar Affective Disorder Type II,
depressed phase, simple phobia and generalized anxiety disorder (GAD) in the last
year

- Lifetime history of schizophrenia, schizoaffective, or other psychotic disorder,
bipolar disorder type I, dementia, dissociative disorders, and sexual and gender
identity disorder

- Personality disorder that makes participation in the trial difficult

- Greater than or equal to 8 episodes of mood disturbance in the previous 12 months

- Greater than 4 unsuccessful treatments in current episode

- History of Substance Abuse or Dependence (DSM-IV) in the last year except nicotine
and caffeine

- Positive urine drug test during screening

- Taking any medication that significantly lowers the seizure threshold (e.g. lithium,
stimulants, bupropion, TCAs, antipsychotics, theophylline, etc.)

- Unstable medical conditions that precludes safe participation in rTMS treatment trial

- Known or suspected pregnancy

- Women of child-bearing potential not using medically accepted form of contraception
when engaged in sexual intercourse

- Any metal or device implants that would increase risk of rTMS

- Unable to determine the motor threshold in the subject

- History of Vagus Nerve Stimulation

- Currently in another investigational study

- Prior electroconvulsive therapy failure