LFMS: Initial Trial in Geriatric Bipolar Depression

The investigators have previously observed mood improvement in participants with bipolar
depression in a population aged 21-60. Here the investigators hope to extend these results to
a similar but new population, geriatric bipolar depression (GPD). In addition to the
evaluation of the effect of multiple treatments, as well as observation of the duration of
the effect after a delay of one week in this population, the investigators will assess
whether this population presents any noticeable difference in tolerance or effect.

The protocol involves five treatments on consecutive days with one follow-up visit; this is a
randomized, double-blind, sham-controlled study (subjects will either receive active
treatment or sham treatment for all five treatment sessions).

The mechanisms of depression in a geriatric population may differ from those in a younger
population. In particular, brain structures and connectivity have changed, and there is the
increased risk of comorbid diagnoses such as dementia that might confound treatment and
assessment. In this study the investigators hope to extend the findings of LFMS in the
general population to directly address the treatment of bipolar depression in a geriatric
population.

Inclusion criteria:

1. Subjects will be men or women aged 55 years or older.

2. Subjects will have a diagnosis of Bipolar Disorder Type I or II, current episode
depressed as measure by a MADRS ≥ 20.

3. Subjects must have failed at least one FDA approved treatment for bipolar depression
before enrolling in this study. Failed treatment is defined as 8 weeks of treatment at
standard dose (Selective Serotonin Reuptake Inhibitors (SSRI) , Selective
Norepinephrine Reuptake Inhibitors (SNRI), mood stabilizer, or typical or atypical
antipsychotic).

4. Subjects must be maintained on a stable dose of all psychotropic medications for a
period of at least two weeks prior to screening.

5. Subjects must be capable of providing informed consent.

Exclusion criteria:

1. Subjects meeting Diagnostic Statistical Manual-IV-TR (DSM-IV-TR) criteria for any Axis
I disorder other than Bipolar Disorder or an anxiety disorder (eg. Major Depressive
Disorder, dementia).

2. Subject has an Mini Mental State Exam (MMSE) score ≤ 24.

3. Subject is pregnant or plans on becoming pregnant.

4. Subject has recent history (within 7 days of screening) of ECT or TMS treatment.

5. Subject has recent history of substance abuse (cannot meet DSM-IV-TR criteria for
substance abuse, no significant drug abuse within last 3 months, no history of
dependence in last year, no drug use within last month, other than marijuana use).

6. Subject has any contraindication for Magnetic Resonance Imaging (MRI) (i.e. Presence
of a pacemaker, neurostimulator, or metal in head or neck).