Depression, Multiple Sclerosis
Conditions
Keywords
Fatty Acids, Omega-3, Fish Oils, Complementary Therapies
Brief summary
This study will determine whether fish oil can reduce depression in people with multiple sclerosis (MS) who are mild to moderately depressed and are currently taking antidepressant medication. Study hypothesis: Three months of fish oil supplementation will improve depression scores on the Montgomery-Asberg depression rating scale (MADRS) or Beck Depression Inventory (BDI) better than placebo.
Detailed description
Depression occurs in 50% to 60% of all individuals with MS. Evidence suggests that the omega-3 fatty acids in fish oil supplements can significantly reduce depression with a low risk of side effects. Therefore, fish oil supplements may be a safe adjunctive therapy to improve the therapeutic benefits of antidepressants. This study will determine the effectiveness of fish oil supplements in reducing depression in MS patients who are taking antidepressant medication. This study will last 3 months. Participants will be randomly assigned to receive either fish oil supplements or placebo daily for 3 months. At the end of 3 months, participants who show an improvement in their depressive symptoms will have the option to continue their treatment for an additional 3 months. Participants will do no respond to treatment will be excused from the study. All participants will remain on their antidepressants and MS medication throughout the study. Participants will have weekly study visits. At each visit, participants will be asked about their general health, and self-report scales will be used to assess depressive symptoms. Medication adherence will be monitored by pill counts and through red blood cell fatty acid analysis. Blood collection will occur at study start and at study completion.
Interventions
DRUGFish oil concentrate
fish oil concentrate at a daily dose of 6 grams (2.1 gram EPA and 1.5 gram DHA).
DRUGPlacebo
soybean oil with 1% fish oil at a daily dose of 6 grams
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of relapsing-remitting MS * Diagnosis of depressive disorder * Score between 11 and 30 on the Montgomery-Asberg Depression Rating Scale (MADRS) * Score of 25 or greater on the Mini-Mental State Examination (MMSE) * Currently taking antidepressant medication for at least 3 months prior to study entry
Exclusion criteria
* Currently taking fatty acid supplements * Consume more than 6 oz of fish per week within 1 month prior to study entry * Severe depression * Suicidal thoughts * Other psychological disorders * Currently taking more than two types of antidepressants * Any serious medical condition that would interfere with the study * Worsening of MS symptoms or corticosteroid treatment within 1 month prior to study entry * Current enrollment in another fish oil study * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) | baseline to 3 months | Higher MADRS scores indicate more severe depression, and the overall score ranges from 0-60. A score of 0-6 indicates symptoms absent, 7-19 indicates mild depression, 20-34 moderate, and \> 34 severe. Our primary outcome was 50% or greater improvement on the Montgomery-Asberg Depression Rating Scale (MADRS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life (SF-36) | baseline to 3 months | SF-36 is a commonly used measure of health-related quality of life and is well validated in many disease conditions. Responses are self-administered and responses are summed into two subscores, the mental component summary (MCS) and physical component summary (PCS). The SF-36 has eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed on a 0-100 scale. Higher scores represent higher function. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants receiving soybean placebo with 1% fish oil at a daily dose of 6 grams. | 18 |
| Fish Oil Concentrate Participants receiving fish oil concentrate at a daily dose of 6 grams (2.1 grams EPA and 1.5 grams DHA) | 21 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo | Fish Oil Concentrate |
|---|---|---|---|
| Adequate antidepressant use | 28 Participants | 12 Participants | 16 Participants |
| Age, Continuous | 51.3 years STANDARD_DEVIATION 1.81 | 51.9 years STANDARD_DEVIATION 10 | 50.7 years STANDARD_DEVIATION 11.6 |
| Beck Depression Inventory (BDI) | 19.97 units on a scale STANDARD_DEVIATION 7.05 | 19.6 units on a scale STANDARD_DEVIATION 5.7 | 20.1 units on a scale STANDARD_DEVIATION 8 |
| Disease duration | 17 years STANDARD_DEVIATION 10.42 | 17.2 years STANDARD_DEVIATION 10 | 16.6 years STANDARD_DEVIATION 9.5 |
| Docosahexaenoic Acid | 4.0 % total fatty acids STANDARD_DEVIATION 1 | 3.9 % total fatty acids STANDARD_DEVIATION 1.2 | 4.0 % total fatty acids STANDARD_DEVIATION 1 |
| Eicosapentaenoic Acid | 0.59 % total fatty acids STANDARD_DEVIATION 0.24 | 0.61 % total fatty acids STANDARD_DEVIATION 0.3 | 0.58 % total fatty acids STANDARD_DEVIATION 0.2 |
| Expanded Disability Status Scale (EDSS) | 3.6 units on a scale STANDARD_DEVIATION 2.3 | 4.1 units on a scale STANDARD_DEVIATION 2.4 | 3.2 units on a scale STANDARD_DEVIATION 2.1 |
| Montgomery-Asberg Depression Rating Scale (MADRS) | 18.75 participants STANDARD_DEVIATION 4.82 | 19.1 participants STANDARD_DEVIATION 4 | 18.4 participants STANDARD_DEVIATION 5.3 |
| Multiple sclerosis modifying therapy (MS DMT) use | 25 Participants | 12 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 39 Participants | 18 Participants | 21 Participants |
| Sex: Female, Male Female | 36 Participants | 17 Participants | 19 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 18 | 11 / 21 |
| serious Total, serious adverse events | 0 / 18 | 0 / 21 |
Outcome results
Primary
Montgomery-Asberg Depression Rating Scale (MADRS)
Higher MADRS scores indicate more severe depression, and the overall score ranges from 0-60. A score of 0-6 indicates symptoms absent, 7-19 indicates mild depression, 20-34 moderate, and \> 34 severe. Our primary outcome was 50% or greater improvement on the Montgomery-Asberg Depression Rating Scale (MADRS).
Time frame: baseline to 3 months
Population: A total of 8 participants discontinued intervention (placebo n = 2, 1 colitis and 1 swallowing problems; treatment n = 6, 2 lost to follow-up, 1 bronchitis, 1 knee surgery, 1 went off antidepressant, 1 travel issues) and did not complete outcome measures
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Montgomery-Asberg Depression Rating Scale (MADRS) | 45.5 percentage of subjects |
| Omega-3 Fatty Acids | Montgomery-Asberg Depression Rating Scale (MADRS) | 47.4 percentage of subjects |
Secondary
Quality of Life (SF-36)
SF-36 is a commonly used measure of health-related quality of life and is well validated in many disease conditions. Responses are self-administered and responses are summed into two subscores, the mental component summary (MCS) and physical component summary (PCS). The SF-36 has eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed on a 0-100 scale. Higher scores represent higher function.
Time frame: baseline to 3 months
Population: A total of 8 participants discontinued (placebo n = 2, 1 colitis, 1 swallowing problems; treatment n = 8, 2 lost to follow-up, 1 bronchitis, 1 knee surgery, 1 went off anti-depressant, 1 travel difficulties) and did not complete measures at end of study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Quality of Life (SF-36) | Physical (PCS) | -0.8 mean change of units on a scale | Standard Error 0.8 |
| Placebo | Quality of Life (SF-36) | Mental (MCS) | 4.2 mean change of units on a scale | Standard Error 1 |
| Omega-3 Fatty Acids | Quality of Life (SF-36) | Physical (PCS) | 1.6 mean change of units on a scale | Standard Error 0.8 |
| Omega-3 Fatty Acids | Quality of Life (SF-36) | Mental (MCS) | 1.5 mean change of units on a scale | Standard Error 1 |