SGA-induced Metabolic Syndrome in Bipolar Youth

This will be a two-phase study design:

Phase I: to prospectively investigate the relationship between baseline LCn-3 fatty acid
status and treatment-emergent adverse cardiometabolic events and weight gain in response to
acute (6-week) open-label quetiapine in first-episode adolescent manic patients (ages 12-17
years). SGA-naïve acutely manic patients will be treated with open-label quetiapine for
6-weeks. Patients will be started on 100 mg BID of quetiapine, and the dose adjusted based
on tolerability and response. The quetiapine target dose is 400-600 mg, with subjects in the
range of 200-500 mg.

Phase II: Patients from Phase I will be randomized to double-blind adjunctive treatment with
LCn-3 fatty acids or placebo for an additional 24 weeks to investigate protective effects on
the progression and resolution of adverse cardiometabolic events and weight gain during
quetiapine maintenance therapy. They will have 6 visits over a 24-week period.

Inclusion Criteria:

- DSM-IV-TR criteria for bipolar disorder, type I, manic or mixed episode

- Baseline YMRS score > 20

- Ages 10-17 years

- Tanner scale stages III-V

- No prior exposure to SGA medications

- Fluent in English

- Provision of written informed consent by a legal guardian and written assent by the
subject

- Manic or depressive symptoms do not result entirely from acute medical illness or
acute intoxication or withdrawal from drugs or alcohol as determined by medical
evaluation and rapid symptom resolution

- If female and of child bearing potential, agrees to use one of the following method
of birth control: complete abstinence from sexual intercourse, barrier (diaphragm or
condom), or oral/injectable contraceptive. For Phase II, additional Inclusion
criteria are

- Receiving a stable therapeutic dose of quetiapine for a minimum of 1 week (i.e.,
patients who achieved remission (YMRS total score 7 during Phase I)

- Not requiring concomitant use of antidepressant or mood-stabilizer medications (see
Section C.4.c. Concomitant Medications).

Exclusion Criteria:

- IQ < 70, as determined by The Wechsler Abbreviated Scale of Intelligence

- Positive pregnancy test (to avoid teratogenesis)

- A history of major cardiovascular or neurological illness

- Any lifetime DSM-IV-TR substance use disorder (nicotine dependence is permitted)

- A lifetime DSM-IV-TR diagnosis of any pervasive developmental disorder

- Any history of a hematological disorder in themselves or a first-degree relative will
be excluded (since omega-3 fatty acids may be associated with anti-thrombotic
effects). Similarly, concomitant use of medications with anticoagulant effects (e.g.
aspirin) will be prohibited

- Allergy to fish/seafood; 8) Currently taking omega-3 fatty acid supplements