Omega-3 and Therapy Study for Depression (OATS)

L. Eugene Arnold

Status and phase: Completed; Phase 1

Conditions: Depression

Treatments: Behavioral: Psychoeducational Psychotherapy (PEP); Drug: Omega-3 Supplementation; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01341925

1R34MH085875-01A2 (U.S. NIH Grant/Contract)

2011H0033

Details and patient eligibility

About

Childhood depression warrants treatment research; including pharmacological and psychotherapeutic interventions. A recent study found fluoxetine to be the only medication with empirical support for decreasing depression in children, but concerns about treatment-emergent suicidal ideation/behavior led the FDA to mandate black-box warning for use of antidepressants in this age group (Bridge et al, 2007). These worries have prompted interest in alternative therapies including dietary supplements such as omega-3 fatty acids (Ω3).

The current study compares Ω3, psychoeducational psychotherapy (PEP), and their combination to a placebo supplement and active monitoring (AM) in a 12-week trial of 60 children with unipolar depression. Primary goals are to determine: 1) feasibility of a) recruiting 60 participants in 24 months; b) retaining participants over a 12-week trial; and 2) effect sizes for Ω3, PEP, and combination treatment. Secondary goals are to explore response curves over time, mediators and moderators, treatment response across an array of outcome variables, adherence to treatment, and side effects. This pilot study of Ω3, PEP, and combined treatment will provide evidence about whether a larger trial is feasible and justifiable.

Full description

Approximately 2 to 4% of children experience either major depressive disorder or dysthymic disorder and 5 to 10% of children and adolescents experience subsyndromal depressive symptoms (Birmaher et al). Due to its prevalence and association with significant functioning deficits, childhood depression warrants treatment research. Treatments include pharmacological and psychotherapeutic interventions. A recent meta-analysis found fluoxetine to be the only medication with empirical support for decreasing depression in children, but concerns about treatment-emergent suicidal ideation/behavior led the FDA to mandate black-box warning for use of antidepressants in this age group (Bridge et al, 2007). These worries have prompted interest in alternative therapies including dietary supplements such as omega-3 fatty acids (Ω3). Research on treatment of mood disorders with Ω3 is promising (Schacter et al, 2005); however, only one RCT has been conducted in children, which was positive (Nemets et al, 2006). Findings from other clinical populations (ADHD, adolescent depression, anxiety and pervasive developmental disorders in children) suggest combination treatments are advantageous (Aman et al., 2009; The MTA Cooperative Group, 1999, 2004; The TADS Team, 2007; Walkup et al., 2008). Little is known about the effectiveness of psychotherapy for children age 12 and under who are clinically depressed. Researchers are beginning to develop and test manual-based individual/family therapies for clinic-referred children with diagnosable depression (Kovacs et al, 2006; Tompson et al, 2007); however, no RCTs have been completed. Prior research supports incorporating psychoeducation about depression, support, and skill building to decrease depressive symptoms (Birmaher et al).

The current study compares Ω3, psychoeducational psychotherapy (PEP), and their combination to a placebo supplement and active monitoring (AM) in a 12-week trial of 60 children with unipolar depression. Primary goals are to determine: 1) feasibility of a) recruiting 60 participants in 24 months; b) retaining participants over a 12-week trial; and 2) effect sizes for Ω3, PEP, and combination treatment. Secondary goals are to explore response curves over time, mediators and moderators, treatment response across an array of outcome variables, adherence to treatment, and side effects. This pilot study of Ω3, PEP, and combined treatment will provide evidence about whether a larger trial is feasible and justifiable.

Enrollment: 73 patients

Sex: All

Ages: 7 to 14 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. aged 7-14 years (boys and girls)
2. DSM-IV-TR diagnosis of major depressive disorder and/or dysthymic disorder as determined by consensus conference
3. Children's Depression Rating Scale (CDRS-R) score ≥ 40
4. full scale IQ ≥ 70
5. child and at least one parent must be able to complete all assessments
6. child must be able to swallow capsules (training in swallowing will be offered)
7. parent/guardian and child must be willing to have blood drawn from child at two study assessments.

Exclusion criteria

1. major medical disorders (eg diabetes, epilepsy, metabolic disorder)
2. inability to communicate in English
3. lack of access via phone
4. autism
5. schizophrenia, or other psychotic states warranting anti-psychotic medication
6. DSM-IV-TR diagnosis of a bipolar disorder
7. active suicidal concern (e.g., "I want to kill myself", a plan for suicide, or an attempt in the past month; however, passive suicidal ideation, such as "I wish I were dead" would not exclude)
8. intake in the previous 4 weeks of supplemental Ω3 fatty acids.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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73 participants in 4 patient groups, including a placebo group

Placebo Supplement and No PEP

Placebo Comparator group

Description:

Will receive two capsules by mouth, two times daily matched for odor and appearance with the active intervention.

Treatment:

Other: Placebo

Omega-3 and PEP

Experimental group

Description:

Omega-3 Supplementation will receive 1000 mg Ω3 (two 500 mg capsules, each containing 350 mg EPA: 50 mg DHA; 100 other Ω3)by mouth, two times daily. Psychoeducational Psychotherapy (PEP)Therapy sessions occur twice a week for up to 24 sessions of manualized treatment.

Treatment:

Drug: Omega-3 Supplementation

Behavioral: Psychoeducational Psychotherapy (PEP)

Omega-3 and No PEP

Experimental group

Description:

Omega-3 Supplementation will receive 1000 mg Ω3 (two 500 mg capsules, each containing 350 mg EPA: 50 mg DHA; 100 other Ω3)by mouth, two times daily.

Treatment:

Drug: Omega-3 Supplementation

Placebo Supplement and PEP

Experimental group

Description:

Placebo Supplement will receive two capsules by mouth, two times daily matched for odor and appearance with the active intervention. Psychoeducational Psychotherapy (PEP)Therapy sessions occur twice a week for up to 24 sessions of manualized treatment.

Treatment:

Behavioral: Psychoeducational Psychotherapy (PEP)