Repetitive Transcranial Magnetic Stimulation (rTMS) for Treatment Resistant Bipolar Depression

The primary objective of this study is to examine the safety and efficacy of rTMS in the
management of treatment-resistant bipolar depression.

Inclusion Criteria:Inclusion Criteria:

- DSM IV Bipolar I or II Disorder with current major depressive episode

- Prior failure to respond to or tolerate at least 2 adequate pharmacotherapy trials

- Ham-D score greater than or equal to 18

Note: site enrolls only one patient per month Exclusion Criteria:Investigators, site
personnel directly affiliated with this study, and their immediate families (immediate
family is defined as a spouse, parent, child or sibling, whether by birth or legal
adoption); b. Individuals diagnosed by the investigator with the following conditions
(current unless other-wise stated): Depression secondary to a general medical condition, or
substance-induced; Seasonal pattern of depression as defined by DSM-IV, History of
substance abuse or dependence within the past year (except nicotine and caffeine); Any
psychotic disorder (lifetime), including schizoaffective disorder, or major depression with
psychotic features in this or previous episodes; Obsessive compulsive disorder (lifetime);
or Post-traumatic stress disorder (current or within the past year). c. An Axis II
Personality Disorder, which in the judgment of the investigator may hinder the patient in
completing the procedures required by the study protocol. d. Individuals with a clinically
defined neurological disorder or insult including, but not limited to: Any condition likely
to be associated with increased intracranial pressure; Space occupying brain lesion; Any
history of seizure EXCEPT those therapeutically induced by ECT; History of cerebrovascular
accident; Transient ischemic attack within two years; Cerebral aneurysm; Dementia; Mini
Mental Status Exam (MMS) score of <24; Parkinson#s disease; Huntington#s chorea; or
Multiple sclerosis.

e. Increased risk of seizure for any reason, including prior diagnosis of increased
intracranial pressure (such as after large infarctions or trauma), or history of
significant head trauma with loss of consciousness for >5 minutes; f. A true positive
response to any question on the Transcranial Magnetic Stimulation Adult Safety Screen
questionnaire (see Attachment H) g. Lifetime treatment with more than 12 antidepressant
medication trials, at any dose or duration, either monotherapy or combination therapy from
the list summarized in Attachment I. h. ECT treatment within 3 months prior to the
screening visit; i. Failure to respond to ECT treatment (i.e., consistent with ATHF level 2
or higher) in this or any previous j. History of treatment with rTMS therapy for any
disorder; k. History of treatment with Vagus Nerve Stimulation; l. Use of any
investigational drug within 4 weeks of the randomization visit; m. Use of fluoxetine within
6 weeks of the randomization visit; n. Use of an MAOI within 2 weeks of the randomization
visit; o. Use of any medication(s) listed on the Excluded Medication List (Attachment J)
within 1 week of the randomization visit; p. Significant acute suicide risk, defined as
follows: Suicide attempt within the previous 6 months that required medical treatment; or
>2 suicide attempts in the past 12 months; or Has a clear-cut plan for suicide and states
that he/she cannot guarantee that he/she will call his/her regular psychiatrist or the
Investigator if the impulse to implement the plan becomes substantial during the study; or
in the investigator#s opinion, is likely to attempt suicide within the next 6 months. q.
Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable
cardiac disease; r. Intracranial implant (e.g., aneurysm clips, shunts, stimulators,
cochlear implants, or electrodes) or any other metal object within or near the head,
excluding the mouth, that cannot be safely removed;s. Known or suspected pregnancy; t. If
participating in psychotherapy, must have been in stable treatment for at least 3 months
prior to entry into the study, with no anticipation of change in the frequency of
therapeutic sessions, or the therapeutic focus over the duration of the rTMS trial; u.
Positive urine drug screen. (A positive urine drug screen at screening may be repeated once
prior to randomization); v. Clinically significant laboratory abnormality, in the opinion
of the investigator; w. Women who are breast-feeding; x. Women of child-bearing potential
not using a medically accepted form of contraception when engaging in sexual intercourse.