Major Depressive Disorder
Conditions
Keywords
Sadness, Insomnia, Loss of appetite, Fatigue, Trouble thinking
Brief summary
The primary objective of the study was to determine the effects of 10-week adjunctive supplementation with 2 doses of LCn-3 fatty acids (fish oil) on cortical functional activity and biochemistry in adolescents with MDD. The primary prediction was that LCn-3 fatty acid supplementation would dose-dependently increase prefrontal cortical functional activation during sustained attention and increase regional biochemical indices of cortical metabolism and integrity concentrations in association with reductions in depressive symptoms.
Detailed description
This study is a 10-week open-label EPA+DHA treatment trial in adolescent (aged 12-18 years) patients with major depressive disorder exhibiting partial response to SSRI medications. After a screening visit, patients were randomized (stratified by gender) to open-label fish oil supplements at a fixed dose of either 2.4 g/day or 15 g/day (2 tablespoons/day) for 10 weeks. A physical examination, a complete blood count (CBC), and thyroid stimulating hormone (TSH) levels were determined at baseline and Week 10, and vital signs (pulse, blood pressure, weight, height, body mass index, temperature) were obtained at each visit. At each visit, safety and tolerability were assessed using a structured side effect interview, the Side Effects Form for Children and Adolescents. At baseline and all weekly visits, depression symptom severity was determined with the Children's Depression Rating Scale-Revised (CDRS-R), a 17-item observer-rated questionnaire, and remission was defined as a CDRS-R score of ≥28. If a patient's depressive symptoms worsened over the course of the trial (defined as 30% worsening relative to baseline on two consecutive visits using CDRS-R scores), they were withdrawn from the study. In view of the potential risk for developing hypomanic symptoms following LCn-3 fatty acid supplementation, manic symptom severity was monitored over the course of the trial with the Young Mania Rating Scale (YMRS), an 11-item observer-rated questionnaire. fMRI scans were performed at baseline and at 10 weeks.
Interventions
Omega-3 Fatty Acids 2.4g/day in capsule form (4 capsules per day)
Liquid omega-3 fatty acid 15 g/day (2 tablespoons/day)
Sponsors
The Inflammation Research Foundation
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
Inclusion Criterion: * Between the ages of 12-18 years. * Diagnosis of MDD and not exhibited symptom remission CDRS-R (\> 28 but \< 40) despite being administered a standard therapeutic dose of an SSRI continuously for a minimum of 6 weeks. * Ability and willingness to provide assent and informed, written consent from at least one biological parent. * Present with biological parent or legal guardian. * Willingness to maintain current dietary habits. * Permission from treating physician * Able to perform fMRI/MRS. Exclusion Criterion: * Inability or unwillingness to provide consent. * Antecedent or concurrent serious medical illness. * Clinically unstable medical disease, including cardiovascular, hepatic insufficiency, severe renal impairment, gastrointestinal, pulmonary, metabolic, endocrine, obesity or other systemic disease. * History of seizures, excluding febrile seizures in childhood. * Patients requiring treatment with any drug which might obscure the action of the study treatment. * Female patients who are either pregnant or lactating. * Clinically significant laboratory abnormalities in the last year on CBC or TSH tests. * Judged clinically to be at suicidal risk (defined as having active suicidal ideation, intent or plan, or a serious suicide attempt within the past 6 months, or a baseline CDRS-R suicide score of \>3). * Hospitalized within the last 3 months * Greater than 1 year outside appropriate age/grade level * Pacemaker * Cerebral aneurysm clip * Cochlear implant * Metal fragments lodged within the eye or braces * Claustrophobia * Necessity of sedation (no sedation will be given). * History of loss of consciousness \> 10 minutes in duration * Allergy to seafood.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mood Symptoms Ratings | 10 weeks | Depression symptom severity was determined with the Children's Depression Rating Scale-Revised (CDRS-R), which is a brief rating scale based on a semi-structured interview with the child. It is a 17-item observer-rated questionnaire where the 17 symptom areas are rated on a 6- or 7-point scale. Total score ranges from a low (not depressed) of 17 to a maximum (very depressed) of 108. Remission was defined as a CDRS-R score of \<28. (The total score is the sum of the ratings on each of the 17 items.) |
Countries
United States
Participant flow
Recruitment details
Recruitment started in August, 2007 at the University of Cincinnati, Medical Sciences Building.
Pre-assignment details
A total of 24 patients were screened and 20 patients met inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| High Dose Fish Oil Liquid omega-3 fatty acid 15 g/day (2 tablespoons/day)
High Dose Fish Oil : Liquid omega-3 fatty acid 15 g/day (2 tablespoons/day) | 8 |
| Low Dose Fish Oil Capsule omega-3 fatty acids 2.4g/day (4 capsules/day)
Low Dose Fish Oil : Omega-3 Fatty Acids 2.4g/day in capsule form (4 capsules per day) | 12 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Refused second scn | 0 | 1 |
Baseline characteristics
| Characteristic | High Dose Fish Oil | Low Dose Fish Oil | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 12 Participants | 20 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 13.3 years STANDARD_DEVIATION 3.2 | 16.7 years STANDARD_DEVIATION 2.9 | 15.0 years STANDARD_DEVIATION 3.05 |
| Depression Score | 33.5 CDRS-R Score STANDARD_DEVIATION 3.1 | 31.9 CDRS-R Score STANDARD_DEVIATION 6.5 | 32.7 CDRS-R Score STANDARD_DEVIATION 4.8 |
| Region of Enrollment United States | 8 participants | 12 participants | 20 participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 14 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 12 |
| serious Total, serious adverse events | 0 / 8 | 2 / 12 |
Outcome results
Primary
Mood Symptoms Ratings
Depression symptom severity was determined with the Children's Depression Rating Scale-Revised (CDRS-R), which is a brief rating scale based on a semi-structured interview with the child. It is a 17-item observer-rated questionnaire where the 17 symptom areas are rated on a 6- or 7-point scale. Total score ranges from a low (not depressed) of 17 to a maximum (very depressed) of 108. Remission was defined as a CDRS-R score of \<28. (The total score is the sum of the ratings on each of the 17 items.)
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline CDRS-R: High Dose Fish Oil | Mood Symptoms Ratings | 33.0 CDRS-R score | Standard Deviation 1.5 |
| Baseline CDRS-R: Low Dose Fish Oil | Mood Symptoms Ratings | 33.1 CDRS-R score | Standard Deviation 1.7 |