Inositol and Omega-3 Fatty Acids in Pediatric Mania

The investigators propose to conduct a randomized, double blind, controlled trial that will
evaluate effectiveness and tolerability of omega-3 fatty acids and inositol used alone and in
combination. The investigators plan to decrease the variability in the population under study
by limiting the age range to 5-12 years and excluding cases with significant, untreated,
comorbidity. The cognitive effects/side effects with a neuropsychological battery pre and
post treatment will be measured. Subjects with a history of failing treatment with two or
more conventional treatments will be excluded.

This will be a 12-week, double-blind, randomized clinical trial study to compare efficacy and
tolerability of the natural treatments omega-3 fatty acids and inositol used in combination
in the treatment of bipolar spectrum disorders in children and adolescents (ages 5-12).
Subjects will be randomized in double blind fashion to one of three arms: omega-3 fatty
acids, inositol or the combined treatment. Further, the proposed study will include measures
of cognition prior to starting study medication and at endpoint. The investigators will
minimize the variability of the population under study by limiting the age range to 5-12
years, minimizing untreated or clinically significant comorbidity and excluding subjects who
have already failed treatment with 2 or more anti-manic agents. Subjects will include youth
ages 5-12 years with a bipolar spectrum disorder (type I, II, or NOS), mixed, manic, or
hypomanic state, according to the Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (American Psychiatric Association, 2000) (DSM-IV), randomized to 3 treatment
arms: 1) treatment with omega-3 fatty acids (N=20); 2) treatment with inositol (N=20); 3)
treatment with the combination of inositol and omega-3 fatty acids (N=20).

Inclusion Criteria:

1. Male or female subjects, 5-12 years of age.

2. Subjects must have a DSM-IV diagnosis of a bipolar spectrum disorder (type I, II, or
Not Otherwise Specified (NOS)), and currently displaying mixed, manic, or hypomanic
symptoms (without psychotic features) according to the DSM-IV based on clinical
assessment and confirmed with structured diagnostic interview (Schedule of Affective
Disorders and Schizophrenia for School-Age Children - Epidemiological Version
(K-SADS-E)) (Orvaschel, 1994).

3. Subjects and their legal representative must have a level of understanding sufficient
to communicate intelligently with the investigator and study coordinator, and to
cooperate with all tests and examinations required by the protocol.

4. Subjects and their legal representative must be considered reliable.

5. Each subject and his/her authorized legal representative must understand the nature of
the study. The subject's authorized legal representative must sign an informed consent
document and the subject must sign an informed assent document.

6. Subjects must have an initial score on the YMRS total score of at least 20.

7. Subject must be able to swallow pills.

8. Subjects with ADHD and ODD will be allowed to participate in the study provided that
the impairment associated with these disorders is of mild or moderate severity (not
severe) and milder in severity relative to the impairment of the bipolar disorder,
according to clinician evaluation. Subjects with comorbid anxiety disorders will be
allowed to participate provided that the impairment associated with the anxiety is of
minimal severity, according to clinician evaluation. Subjects with comorbid CD will be
excluded.

Exclusion Criteria:

1. Investigator and his/her immediate family; defined as the investigator's spouse,
parent, child, grandparent, or grandchild.

2. Serious or unstable illness including hepatic, renal, gastroenterological,
respiratory, cardiovascular (including ischemic heart disease), endocrinologic,
neurologic, immunologic, or hematologic disease.

3. History of bleeding diathesis, including those with von Willebrand disease.

4. Uncorrected hypothyroidism or hyperthyroidism.

5. History of sensitivity to omega-3 fatty acids or inositol. A non-responder or history
of intolerance to omega-3 fatty acid or inositol, after 2 months of treatment at
adequate doses as determined by the clinician.

6. Severe allergies or multiple adverse drug reactions.

7. Failed 2 or more previous trials with anti-manic treatments including lithium,
anticonvulsants and atypical antipsychotic medication.

8. Current or past history of seizures.

9. DSM-IV substance use, abuse or dependence (unlikely in ages 5-12).

10. Judged clinically to be at serious suicidal risk.

11. Current diagnosis of schizophrenia.

12. Current diagnosis of conduct disorder

13. Pregnancy (unlikely in ages 5-12).

14. YMRS Item #8 (Content) score of 8 ("delusions; hallucinations").

15. YMRS total score above 40.

16. Girls who have begun menstruating.

17. C-SSRS score ≥ 4.

18. IQ < 70.