Omega-3 fatty acids
A series of reviews focusing on omega-3 fatty acids in depression have been published in recent years. The review by Williams et al (2006) only searched for studies published up to 2001 and included varied study types. Appleton et al (2006) searched up to June 2006 and found 18 randomized controlled trials, 12 of which reported data that could be included in a meta-analysis. The authors reported that trial evidence was limited and difficult to summarize and evaluate because of considerable heterogeneity. However, results from 6 trials in patients with major depression were combined with trials in patients with depressed mood associated with other psychiatric or medical conditions. One of these was a large trial in angina sufferers which reported no effects. The authors concluded that the evidence available provides little support for the use of omega-3 fatty acids to improve depressed mood. Lin and Su (2007) found 10 double-blind, placebo-controlled studies (329 patients in total) by searching the literature up to August 2006. Studies included patients with depression and those with bipolar disorder. An effect size of 0.61 was calculated by the authors who reported that omega-3 fatty acids significantly improved depression in patients with clearly defined depression. Due to publication bias and heterogeneity, more large-scale trials are required and Lin and Su suggest that these should be directed at defining the most appropriate target group, the therapeutic dose of EPA, and the composition of omega-3 fatty acids in treating depression. A Cochrane review on this topic has been planned (Silvers et al 2003).
Systematic reviews
Appleton KM, Hayward RC, Gunnell D, Peters TJ, Rogers PJ, Kessler D, Ness AR. Effects of n-3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials. American Jourbal of Clinical Nutrition. 2006, 84(6):1308-16. [Full text]
Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. Journal of Clinical Psychiatry. 2007, 68(7):1056-61. [PubMed abstract] [DARE provisional record]
Williams AL, Katz D, Ali A, Girard C, Goodman J, Bell I. Do essential fatty acids have a role in the treatment of depression? Journal of Affective Disorders. 2006, 93(1-3):117-23. [Pubmed abstract]
Systematic reviews on mental illness in general
Clayton EH, Hanstock TL, Garg ML, Hazell PL. Long chain omega-3 polyunsaturated fatty acids in the treatment of psychiatric illnesses in children and adolescents. Acta Neuropsychiatrica. 2007,19(2):92-103. [Abstract]
Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, et al. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. Journal of Clinical Psychiatry. 2006, 67(12):1954-67. [PubMed abstract] (meta-analyses of various disorders including major depression)
Ross BM, Seguin J, Sieswerda LE. Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid? Lipids in Health and Disease. 2007, 6:21. [Full text]
Schachter H, Kourad K, Merali Z, Lumb A, Tran K, Miguelez M, et al. Effects of Omega-3 Fatty Acids on Mental Health. Evidence Report/Technology Assessment No. 116. (Prepared by the University of Ottawa Evidence-based Practice Center, Under Contract No. 290-02-0021.) AHRQ Publication No. 05-E022-2. Rockville, MD: Agency for Healthcare Research and Quality. July 2005. [Full text]
Randomized controlled trials (RCTs)
Freeman MP, Hibbeln J, Wisner K, Watchman M, Brumbach B, Hill R, et al. Double-blind dose-finding study of omega-3 fatty acids for postpartum depression. Neuropsychopharmacology. 2004;29 Suppl 1:S102.
Freeman MP, Hibbeln JR, Wisner KL, Brumbach BH, Watchman M, Gelenberg AJ. Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression. Acta Psychiatrica Scandinavica. 2006, 113(1):31-5. [PubMed abstract]
Freeman MP, Sinha P. Tolerability of omega-3 fatty acid supplements in perinatal women. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2007, 77(3-4):203-8. [PubMed abstract]
Grenyer BF, Crowe T, Meyer B, Owen AJ, Grigonis-Deane EM, Caputi P, et al. Fish oil supplementation in the treatment of major depression: a randomised double-blind placebo-controlled trial. Progress in Neuropsychopharmacology and Biological Psychiatry. 2007, 31(7):1393-6. [PubMed abstract]
Nemets H, Nemets B, Apter A, Bracha Z, Belmaker RH. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. American Journal of Psychiatry. 2006 Jun;163(6):1098-100. [Full text]
Rees AM, Parker GB, Owen CA. Omega-3 polyunsaturated fatty acids as a treatment for major depression. Australian and New Zealand Journal of Psychiatry. 2005, 39 Suppl 2:A52.
Rogers PJ, Appleton KM, Kessler D, Peters TJ, Gunnell D, Hayward RC, et al. No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial. British Journal of Nutrition. 2008 99(2):421-31. [PubMed abstract]
Silvers KM, Woolley CC, Hamilton FC, Watts PM, Watson RA. Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2005 Mar;72(3):211-8. [PubMed abstract]
Ongoing studies
Carney RM. Omega-3 for depression and other cardiac risk factors. controlled-trials.com 2006. NCT00116857.
Silvers KM, Hackett ML, Scott KM. Omega 3 fatty acids for depression. (Protocol) Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD004692. DOI: 10.1002/14651858.CD004692. [Full text]
Folate
Systematic review
Taylor MJ, Carney SM, Goodwin GM, Geddes JR. Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. Journal of Psychopharmacology. 2004, 18(2):251-6. [PubMed abstract] Duplicate publication of 2003 Cochrane review.
Randomized controlled trials (RCTs)
Liu CJ, Ning YL, Jia ZL, et a. [The plumentary therapeutic efficiency of folic acid for depression] [Chinese]. Chinese Journal of Behavioral Medical Science. 2004;13:169-70.
Ongoing studies
Christensen H. Beyond Ageing Project: A Randomized Controlled Trial to Assess the Benefit of Improving Mental Health Literacy in Depression as Well as the Effect of Folate and B12, and Physical Activity, in Preventing Major Depression and Cognitive Impairment Among Australians Aged 65-74 Years. clinicaltrials.gov 2005. NCT00214682.
Roberts SH, Bedson E, Hughes D, Lloyd K, Moat S, Pirmohamed M, et al. Folate augmentation of treatment - evaluation for depression (FolATED): protocol of a randomised controlled trial. BMC Psychiatry. 2007, 7:65. [Full text]
Other articles of interest
Gilbody S, Lightfoot T, Sheldon T. Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity. Journal of Epidemiology and Community Health. 2007, 61(7):631-7. [PubMed abstract]
Inositol
Systematic review
Taylor MJ, Wilder H, Bhagwagar Z, Geddes J. Inositol for depressive disorders. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD004049. DOI: 10.1002/14651858.CD004049.pub2. [Full text]
SAMe
Systematic review
Williams AL, Girard C, Jui D, Sabina A, Katz DL. S-adenosylmethionine (SAMe) as treatment for depression: a systematic review. Clininical and Investigative Medicine. 2005, 28(3):132-9. [PubMed abstract]
Vitamin B6
Systematic review
Williams AL, Cotter A, Sabina A, Girard C, Goodman J, Katz DL. The role for vitamin B-6 as treatment for depression: a systematic review. Family Practice. 2005, 22(5):532-7. [Full text]
Evidence on other supplements
Randomized controlled trials (RCTs)
Booij L, Merens W, Markus CR, Van-Der-Does AJW. Diet rich in alpha-lactalbumin improves memory in unmedicated recovered depressed patients and matched controls. Journal of Psychopharmacology. 2006, 20:526-35. [PubMed abstract]
Gariballa S, Forster S. Effects of dietary supplements on depressive symptoms in older patients: a randomised double-blind placebo-controlled trial. Clinical Nutrition. 2007, 26(5):545-51. [PubMed abstract]
Hvas AM, Juul S, Lauritzen L, Nexo E, Ellegaard J. No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. Journal of Affective Disorders. 2004, 81(3):269-73. [PubMed abstract]
Ille R, Spona J, Zickl M, Hofmann P, Lahousen T, Dittrich N, et al. "Add-On"-therapy with an individualized preparation consisting of free amino acids for patients with a major depression. European Archives of Psychiatry and Clinical Neuroscience. 2007, 257(4):222-9. [PubMed abstract]
Merens W, Booij L, Markus R, Zitman FG, Onkenhout W, Van der Does AJ. The effects of a diet enriched with alpha-lactalbumin on mood and cortisol response in unmedicated recovered depressed subjects and controls. British Journal of Nutrition. 2005, 94(3):415-22. [PubMed abstract]
Safety
Werneke U. Risk management of nutritional supplements in chronic illness: the implications for the care of cancer and depression. Proceedings of the Nutrition Society. 2007, 66(4):483-92. [PubMed abstract]
Link back to 2008 Annual evidence update on CAM in depression
