Do Omega-3 Fatty Acids Have an Antidepressant Effect in Patients With Signs of Peripheral Inflammation?

NCT03143075 | Completed DMC

• 1 other identifier: 2017150
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the investigators will stratify depressed subjects a priori based on CRP levels to test the hypothesis that eicosapentaenoic (EPA) would be more efficacious to treat depression in subjects with high CRP levels compared to subjects with low CRP levels. Depressed subjects, with ongoing stabilized antidepressive treatment who remain clinically depressed, will be enrolled in an "Inflammation group" or in a "Non-inflammation group" depending on baseline levels of CRP. Subjects in both groups will receive EPA enriched omega-3 fatty acids for 8 weeks, added to their pre-stabilized antidepressant medication.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Reduction in depressive symptoms

  Absolute difference between baseline and week 8 of the total sum of the HAM-D-17

  8 weeks

Secondary Outcomes (18)

• Response

  8 weeks

• Change in depressed mood

  8 weeks

• Absolute change in "inflammatory depressive symptoms"

  8 weeks

• Improvement in functioning and quality of life.

  8 weeks

• Absolute change in general Anxiety symptoms

  8 weeks

Study Arms (2)

Inflammation group

ACTIVE COMPARATOR

Subjects with CRP≥3, will receive eicosapentaenoic acid enriched omega-3 fatty acids, 2 g/day, for 8 weeks, added to their pre-stabilized antidepressant medication

Dietary Supplement: Eicosapentaenoic acid enriched omega-3 fatty acids, 2 g/day

Non-inflammation group

ACTIVE COMPARATOR

Subjects with CRP\<3, will receive eicosapentaenoic acid enriched omega-3 fatty acids, 2 g/day, for 8 weeks, added to their pre-stabilized antidepressant medication

Dietary Supplement: Eicosapentaenoic acid enriched omega-3 fatty acids, 2 g/day

Interventions

Eicosapentaenoic acid enriched omega-3 fatty acids, 2 g/day DIETARY_SUPPLEMENT

Eicosapentaenoic acid enriched omega-3 fatty acids, 2 g/day, added to pre-stabilized antidepressant medication

Inflammation group; Non-inflammation group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female, aged 18-80.
• Fulfilling the DSM criteria for a current depressive episode, unipolar (symptom duration\> 4 weeks) as determined by the study physician
• HAM-D-17 score ≥ 15 (Rapaport, Nierenberg et al. 2016)
• A Clinical Global Impression Severity Score ≥ 3 (Rapaport, Nierenberg et al. 2016)
• All subjects should be stable on antidepressants or mood stabilizers ≥6 weeks.
• Willing to not significantly modify their diet from the time they sign consent through the end of study participation.

You may not qualify if:

• Serious or unstable medical illness that in the investigator's opinion could compromise response to treatment or interpretation of study results. Examples: Malignancy not in remission for at least 1 year, Active autoimmune disorder or inflammatory bowel disease, Insulin-dependent diabetes mellitus.
• Known or suspected allergy to the study compounds.
• Ongoing infection.
• Ongoing pregnancy or breast-feeding
• A diagnosis of psychotic disorder, bipolar disorder, mental retardation dementia, or individual whom, due to other causes, lack the ability to make an informed decision.
• Ongoing ECT.
• Concomitant use of anticoagulants or known bleeding disorder.
• Patients who, in the investigator's judgment, pose a current, serious suicidal or homicidal risk.
• A diagnosis for any Substance Use Disorder (except nicotine or caffeine) in the 3 months prior to the screening visit.
• Any medications (within 1 week of baseline or during the trial) that might confound the biomarker findings, including: Regular ingestion of NSAIDs or COX-2 inhibitors, or any use of oral steroids, immunosuppressants, interferon, chemotherapy (Patients will be instructed not to take an NSAID, COX-2 inhibitor or Aspirin in the 24 hours prior to a biomarker assessment visit).
• Patients who have taken supplements with omega-3 fatty acids for more than three consecutive days in the preceding month.
• Within 4 weeks of starting psychotherapy or planning to start psychotherapy during the study
• Active participation in other clinical studies with ongoing study visits

Sponsors & Collaborators

• Region Skane: lead
• University of California, San Francisco: collaborator

Study Sites (1)

Lund University, Dept of Psychiatry

Lund, 221 85, Sweden

Location

Related Publications (18)

• Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010 Mar 1;67(5):446-57. doi: 10.1016/j.biopsych.2009.09.033. Epub 2009 Dec 16.

  PMID: 20015486 BACKGROUND

• Raison CL, Demetrashvili M, Capuron L, Miller AH. Neuropsychiatric adverse effects of interferon-alpha: recognition and management. CNS Drugs. 2005;19(2):105-23. doi: 10.2165/00023210-200519020-00002.

  PMID: 15697325 BACKGROUND

• Jokela M, Virtanen M, Batty GD, Kivimaki M. Inflammation and Specific Symptoms of Depression. JAMA Psychiatry. 2016 Jan;73(1):87-8. doi: 10.1001/jamapsychiatry.2015.1977. No abstract available.

  PMID: 26579988 BACKGROUND

• Raison CL, Miller AH. Is depression an inflammatory disorder? Curr Psychiatry Rep. 2011 Dec;13(6):467-75. doi: 10.1007/s11920-011-0232-0.

  PMID: 21927805 BACKGROUND

• Miller AH, Haroon E, Felger JC. Therapeutic Implications of Brain-Immune Interactions: Treatment in Translation. Neuropsychopharmacology. 2017 Jan;42(1):334-359. doi: 10.1038/npp.2016.167. Epub 2016 Aug 24.

  PMID: 27555382 BACKGROUND

• Rapaport MH, Nierenberg AA, Schettler PJ, Kinkead B, Cardoos A, Walker R, Mischoulon D. Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-concept study. Mol Psychiatry. 2016 Jan;21(1):71-9. doi: 10.1038/mp.2015.22. Epub 2015 Mar 24.

  PMID: 25802980 BACKGROUND

• Lindqvist D, Epel ES, Mellon SH, Penninx BW, Revesz D, Verhoeven JE, Reus VI, Lin J, Mahan L, Hough CM, Rosser R, Bersani FS, Blackburn EH, Wolkowitz OM. Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging. Neurosci Biobehav Rev. 2015 Aug;55:333-64. doi: 10.1016/j.neubiorev.2015.05.007. Epub 2015 May 18.

  PMID: 25999120 BACKGROUND

• Babcock T, Helton WS, Espat NJ. Eicosapentaenoic acid (EPA): an antiinflammatory omega-3 fat with potential clinical applications. Nutrition. 2000 Nov-Dec;16(11-12):1116-8. doi: 10.1016/s0899-9007(00)00392-0. No abstract available.

  PMID: 11118844 BACKGROUND

• Rangel-Huerta OD, Aguilera CM, Mesa MD, Gil A. Omega-3 long-chain polyunsaturated fatty acids supplementation on inflammatory biomakers: a systematic review of randomised clinical trials. Br J Nutr. 2012 Jun;107 Suppl 2:S159-70. doi: 10.1017/S0007114512001559.

  PMID: 22591890 BACKGROUND

• Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol. 2013 Mar;75(3):645-62. doi: 10.1111/j.1365-2125.2012.04374.x.

  PMID: 22765297 BACKGROUND

• Kiecolt-Glaser JK, Epel ES, Belury MA, Andridge R, Lin J, Glaser R, Malarkey WB, Hwang BS, Blackburn E. Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial. Brain Behav Immun. 2013 Feb;28:16-24. doi: 10.1016/j.bbi.2012.09.004. Epub 2012 Sep 23.

  PMID: 23010452 BACKGROUND

• Saunders EF, Ramsden CE, Sherazy MS, Gelenberg AJ, Davis JM, Rapoport SI. Omega-3 and Omega-6 Polyunsaturated Fatty Acids in Bipolar Disorder: A Review of Biomarker and Treatment Studies. J Clin Psychiatry. 2016 Oct;77(10):e1301-e1308. doi: 10.4088/JCP.15r09925.

  PMID: 27631140 BACKGROUND

• Bloch MH, Hannestad J. Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. Mol Psychiatry. 2012 Dec;17(12):1272-82. doi: 10.1038/mp.2011.100. Epub 2011 Sep 20.

  PMID: 21931319 BACKGROUND

• Mocking RJ, Harmsen I, Assies J, Koeter MW, Ruhe HG, Schene AH. Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder. Transl Psychiatry. 2016 Mar 15;6(3):e756. doi: 10.1038/tp.2016.29.

  PMID: 26978738 BACKGROUND

• 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. doi: 10.1016/s0924-977x(03)00032-4.

  PMID: 12888186 BACKGROUND

• Hieronymus F, Emilsson JF, Nilsson S, Eriksson E. Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression. Mol Psychiatry. 2016 Apr;21(4):523-30. doi: 10.1038/mp.2015.53. Epub 2015 Apr 28.

  PMID: 25917369 BACKGROUND

• Suneson K, Soderberg Veiback G, Lindahl J, Tjernberg J, Stahl D, Ventorp S, Angeby F, Lundblad K, Wolkowitz OM, Lindqvist D. Omega-3 fatty acids for inflamed depression - A match/mismatch study. Brain Behav Immun. 2024 May;118:192-201. doi: 10.1016/j.bbi.2024.02.029. Epub 2024 Mar 1.

  PMID: 38432599 DERIVED

• Suneson K, Angeby F, Lindahl J, Soderberg G, Tjernberg J, Lindqvist D. Efficacy of eicosapentaenoic acid in inflammatory depression: study protocol for a match-mismatch trial. BMC Psychiatry. 2022 Dec 19;22(1):801. doi: 10.1186/s12888-022-04430-z.

  PMID: 36536364 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Raters are blind to "Inflammation group" or "Non-inflammation group" allocation
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Match/mismatch design (based on CRP levels), all subjects receive the same dose of EPA, no one receives placebo. Raters are blind to "Inflammation group" or "Non-inflammation group" allocation

Study Record Dates

• First Submitted: April 20, 2017
• First Posted: May 8, 2017
• Study Start: August 1, 2017
• Primary Completion: May 9, 2023
• Study Completion: May 9, 2023
• Last Updated: November 18, 2023

Record last verified: 2023-03

Locations

SE (1)