Fish Oil for the Treatment of Depression in Patients With Multiple Sclerosis

• Sponsor: Oregon Health and Science University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00122954
• Collaborator: National Center for Complementary and Integrative Health (NCCIH) (NIH)
• Enrollment: 39
• Location: 1
• Arms: 2
• Duration (Months): 47
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis; Depression	Drug: Fish oil concentrate; Drug: Placebo	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Fish Oil as an Adjunct Therapy for Depression in Multiple Sclerosis
• Study Start Date: Jul 1, 2005
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fish oil concentrate Fish oil concentrate	Drug: Fish oil concentrate; fish oil concentrate at a daily dose of 6 grams (2.1 gram EPA and 1.5 gram DHA).; Other Names: omega-3 fatty acids
Placebo Comparator: Placebo oil Placebo oil	Drug: Placebo; soybean oil with 1% fish oil at a daily dose of 6 grams

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oregon Health and Science University	Portland	Oregon	United States	97239

Sponsors and Collaborators

• Oregon Health and Science University
• National Center for Complementary and Integrative Health (NCCIH)

Investigators

• Principal Investigator: Lynne Shinto, ND, MPH, Oregon Health and Science University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for more information about complementary and alternative medicine-related research at Oregon Health and Science University
• Click here for more information about research studies at the Multiple Sclerosis Center of Oregon

Publications

• Nemets B, Stahl Z, Belmaker RH. Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am J Psychiatry. 2002 Mar;159(3):477-9.
• Peet M, Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry. 2002 Oct;59(10):913-9.
• Su KP, Huang SY, Chiu CC, Shen WW. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol. 2003 Aug;13(4):267-71. Erratum in: Eur Neuropsychopharmacol. 2004 Mar;14(2):173.

• Responsible Party: Lynne Shinto, Lynn Shinto, ND, MPH, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT00122954
• Other Study ID Numbers: K23AT002155-01; K23AT002155-01
• First Posted: Jul 22, 2005
• Last Update Posted: Jun 8, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Lynne Shinto, Lynn Shinto, ND, MPH, Oregon Health and Science University: Fatty Acids, Omega-3; Fish Oils; Complementary Therapies
• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; Depression; Depressive Disorder

Study Results

Participant Flow

Arm/Group Title	Placebo	Omega-3 Fatty Acids
Arm/Group Description	Participants randomized to the placebo group received capsules that contained soybean oil with 1% fish oil so that it was flavored to taste and smell similar to the fish oil capsules.	Participants randomized to the omega-3 FA group received capsules in the form of fish oil concentrate (triglyceride form) at a daily dose of 6 grams (1.95 grams of EPA and 1.45 grams of DHA).
Period Title: Overall Study
STARTED	18	21
COMPLETED	16	18
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Placebo	Fish Oil Concentrate	Total
Arm/Group Description	Participants receiving soybean placebo with 1% fish oil at a daily dose of 6 grams.	Participants receiving fish oil concentrate at a daily dose of 6 grams (2.1 grams EPA and 1.5 grams DHA)	Total of all reporting groups
Overall Participants	18	21	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.9 (10.0)	50.7 (11.6)	51.3 (1.81)
Sex: Female, Male (Count of Participants)
Female	17 94.4%	19 90.5%	36 92.3%
Male	1 5.6%	2 9.5%	3 7.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	18 100%	21 100%	39 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Disease duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	17.2 (10.0)	16.6 (9.5)	17 (10.42)
Expanded Disability Status Scale (EDSS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.1 (2.4)	3.2 (2.1)	3.6 (2.3)
Montgomery-Asberg Depression Rating Scale (MADRS) (participants) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [participants]	19.1 (4.0) 106.1%	18.4 (5.3) 87.6%	18.75 (4.82) 48.1%
Beck Depression Inventory (BDI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	19.6 (5.7)	20.1 (8.0)	19.97 (7.05)
Eicosapentaenoic Acid (% total fatty acids) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% total fatty acids]	0.61 (0.3)	0.58 (0.2)	0.59 (0.24)
Docosahexaenoic Acid (% total fatty acids) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% total fatty acids]	3.9 (1.2)	4.0 (1.0)	4.0 (1.0)
Adequate antidepressant use (Count of Participants)
Count of Participants [Participants]	12 66.7%	16 76.2%	28 71.8%
Multiple sclerosis modifying therapy (MS DMT) use (Count of Participants)
Count of Participants [Participants]	12 66.7%	13 61.9%	25 64.1%

Outcome Measures

1. Primary Outcome

Title	Montgomery-Asberg Depression Rating Scale (MADRS)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Omega-3 Fatty Acids
Arm/Group Description	Participants randomized to the placebo group received capsules that contained soybean oil with 1% fish oil so that it was flavored to taste and smell similar to the fish oil capsules.	Participants randomized to the omega-3 FA group received capsules in the form of fish oil concentrate (triglyceride form) at a daily dose of 6 grams (1.95 grams of EPA and 1.45 grams of DHA).
Measure Participants	16	15
Number [percentage of subjects]	45.5	47.4

2. Secondary Outcome

Title	Quality of Life (SF-36)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Omega-3 Fatty Acids
Arm/Group Description	Participants randomized to the placebo group received capsules that contained soybean oil with 1% fish oil so that it was flavored to taste and smell similar to the fish oil capsules.	Participants randomized to the omega-3 FA group received capsules in the form of fish oil concentrate (triglyceride form) at a daily dose of 6 grams (1.95 grams of EPA and 1.45 grams of DHA).
Measure Participants	16	15
Physical (PCS)	-0.8 (0.8)	1.6 (0.8)
Mental (MCS)	4.2 (1.0)	1.5 (1.0)

Adverse Events

Time Frame	Adverse event data were collected from baseline to end of study at 3 months
Adverse Event Reporting Description	Participants were monitored twice a month (either in clinic or by phone) for general health events, worsening of depression (>30 Beck's Depression Inventory), and suicidal ideation. Worsening of depression or MS-related symptoms would result in referrals for care and withdrawal from the study. General adverse events were assessed by type, severity, relationship to supplement, action taken, and outcome.
Arm/Group Title	Placebo		Omega-3 Fatty Acids
Arm/Group Description	Participants randomized to the placebo group received capsules that contained soybean oil with 1% fish oil so that it was flavored to taste and smell similar to the fish oil capsules.		Participants randomized to the omega-3 FA group received capsules in the form of fish oil concentrate (triglyceride form) at a daily dose of 6 grams (1.95 grams of EPA and 1.45 grams of DHA).
All Cause Mortality
	Placebo		Omega-3 Fatty Acids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Omega-3 Fatty Acids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Omega-3 Fatty Acids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/18 (88.9%)		11/21 (52.4%)
Cardiac disorders
arrhythmia	0/18 (0%)	0	1/21 (4.8%)	1
Gastrointestinal disorders
diarrhea	1/18 (5.6%)	1	1/21 (4.8%)	1
nausea	0/18 (0%)	0	1/21 (4.8%)	1
colitis	1/18 (5.6%)	1	0/21 (0%)	0
Immune system disorders
multiple sclerosis relapse	3/18 (16.7%)	3	0/21 (0%)	0
fatigue	3/18 (16.7%)	3	0/21 (0%)	0
Infections and infestations
cold or flu	3/18 (16.7%)	3	3/21 (14.3%)	3
Nervous system disorders
numbness and tingling	2/18 (11.1%)	2	0/21 (0%)	0
dizziness	1/18 (5.6%)	1	1/21 (4.8%)	1
Renal and urinary disorders
Urinary Tract Infection	4/18 (22.2%)	4	0/21 (0%)	0
Reproductive system and breast disorders
prolonged menstruation	0/18 (0%)	0	1/21 (4.8%)	1
Skin and subcutaneous tissue disorders
bruising	0/18 (0%)	0	3/21 (14.3%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.