Neurochemical Effects of Omega-3 Fatty Acids in Adolescents at Risk for Mania
Condition: Mania
MeSH terms: Mania
Intervention: OMega 3; Placebo
Intervention description: Individual omega-3 capsules contain 400 mg EPA and 200 mg DHA taken twice a day; Placebo given twice a day which will be compared to Omega 3
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 55.0
Sex: All
Minimum age: 10 Years
Maximum age: 21 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Mania; Adolescents at risk for Mania

Summary:

      The purpose of this study is to see if taking a substance called omega-3 fatty acids is
      effective, safe, and well-tolerated for treating adolescents with major depressive disorder
      (also called simply "depression" or "clinical depression"). Another purpose of this study is
      to see how much omega-3 fatty acids are in a patient's blood and if that makes the patient
      more or less likely to develop mania (i.e. periods of irritability or extreme silliness
      accompanied by decreased need for sleep, risky behaviors, feeling like the patient has
      special abilities, inability to sit still, and rapid speech) in the future. Yet another
      purpose of this study is to see how taking omega-3 fatty acids affect brain scans. Omega-3
      fatty acids are not United States Food and Drug Administration (FDA)-approved to treat
      depression in adults or in children and adolescents.

      Omega-3 fatty acids can only be obtained through diet, most often from fish and other sea
      foods, though they are also found in other food sources such as flax seed. Omega-3 fatty
      acids have been shown to play a role in affecting brain chemicals responsible for regulating
      mood and have been found to reduce symptoms of depression in medicated-patients with major
      depressive disorder.

      By completing this study, the investigators hope to better understand who benefits from
      treatment, why they do or do not respond to medications, and who is at greater risk for
      developing further mental illness. With this information, the investigators hope to be able
      to improve treatment and outcome in people with major depressive disorder.
    

Eligibility criteria:

        Inclusion Criterion:

          -  Ages 10-21 years old.

          -  At least one biological parent with bipolar I disorder.

          -  Meets DSM-IV-TR 80 criteria for major depressive disorder (MDD or Depressive Disorder
             NOS at screening as determined by the Washington University at St. Louis Kiddie
             Schedule for Affective Disorders and Schizophrenia, WASH-U-KSADS;81

          -  Childhood Depression Rating Scale-Revised Version40,41(CDRS-R) scores greater than or
             equal to 40 at screening and baseline.

          -  Fluent in English.

          -  Provision of written informed consent/assent as previously described.

          -  Agrees to use one of the following method of birth control: complete abstinence from
             sexual intercourse, barrier (diaphragm or condom), or oral/injectable contraceptive.

        Exclusion Criterion:

          -  Contraindication to an MRI scan (e.g., metal clips, braces or claustrophobia).

          -  Mood symptoms resulting from acute medical illness or acute intoxication or withdrawal
             from drugs or alcohol as determined by careful medical evaluation or rapid symptom
             resolution.

          -  Psychotic symptoms (i.e., hallucinations or delusions).

          -  Any lifetime history of a manic or hypomanic episode.

          -  Any lifetime diagnosis of bipolar disorder not otherwise specified (NOS) or
             cyclothymia or a current diagnosis of depressive disorder NOS. A current diagnosis of
             dysthymia will not be exclusionary, if the adolescent also has a current diagnosis of
             MDD.

          -  A history of a major medical (e.g. diabetes) or neurological illness, laboratory
             abnormalities, or a significant episode (> 10 minutes) of loss of consciousness that
             could influence the MRS results, as determined by a study physician.

          -  Any history of alcohol or drug dependence (nicotine dependence is permitted).

          -  Allergy to shellfish or seafood.

          -  Mental retardation (IQ<70) as determined by the Wechsler Abbreviated Scale of
             Intelligence (WASI), administered by a research coordinator who is a trained
             psychometrician.

          -  A positive serum pregnancy test or lactating.

          -  A history of intolerance, hypersensitivity or non-response to omega-3 fatty acids.

          -  Any history of a hematological disorder in themselves or a first-degree relative,
             since omega-3 fatty acids may be associated with anti-coagulant effects.

          -  Concomitant use of medications with anticoagulant effects (e.g. aspirin).

          -  A lithium or valproate serum level of >0.4 mEq/L and 30 mg/L, respectively at
             baseline.

          -  Use of antipsychotics, other mood stabilizers, stimulants (if opting to discontinue),
             or atomoxetine within 72 hours (aripiprazole within two weeks will be exclusionary
             because of its long half-life) or antidepressants within 5 days (fluoxetine within one
             month will be exclusionary because of its long half-life). Patients treated with a
             depot antipsychotic within one dosing interval of baseline will be excluded. Subjects
             diagnosed with ADHD and taking a stable dose of stimulants for the previous month will
             be permitted to continue if it is determined necessary by subject, primary caregiver,
             and treating clinician report in conjunction with the study physician.

          -  Concomitant use of other psychotropic medications or medications with central nervous
             system (CNS) effects within 5 half-lives from baseline MRI scan or prior treatment
             with a medication with CNS effects that requires more than 5 days of a screening
             period.

          -  Any psychiatric symptom that requires admission to an inpatient psychiatric hospital,
             as determined by a study physician.

          -  Any initiated psychotherapy within 2 months prior to the screening visit, or plans to
             initiate psychotherapy during study participation. Adolescents who present with their
             current depressive episode despite longer-term psychotherapy (i.e., >2 months) may be
             included. For participants who enter the study on psychotherapy, the type and
             frequency of therapy will remain constant during the study.