This study will test the effectiveness of two different kinds of omega-3 fatty acid dietary supplements in treating the symptoms of major depression.

Major depression is a common mental disorder that affects millions of people each year. It can severely impact a person's life, causing someone to often feel sad and hopeless, as well as affect a person's sleep patterns, concentration, and energy levels. Despite the availability of numerous therapies, current treatments are not ideal for some people. Recently, some research has shown that an increase in dietary intake of polyunsaturated fatty acids (PUFAs), such as omega-3 fatty acid, might help treat depression. Eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) are two common types of PUFAs high in omega-3 fatty acids and are available in low dosages in some dietary supplements. The purpose of this study is to compare the effectiveness of an EPA-enriched mixture versus pure DHA versus a placebo in treating the symptoms of major depression.

Participants in this double blind study will be randomly assigned to one of three study groups. Participants assigned to the first study group will receive capsules containing 500 mg of an EPA-enriched omega-3 fatty acid preparation. Participants assigned to the second study group will receive capsules containing 500 mg of pure DHA. Participants assigned to the third study group will receive capsules containing a placebo. The study will last approximately 9 weeks. This will include an initial screening the first week followed by an 8-week period during which all participants will take two capsules of their assigned treatment each morning. Participants will attend a total of six study visits. The initial visit will last approximately 2 hours and will include a psychiatric assessment, urine and blood collection, an electrocardiogram (EKG), and a Food Processor Questionnaire. Participants who qualify for further participation will then enter a 1-week washout period during which they will stop taking any current psychotropic medication. At the second study visit, participants will be assigned to their treatment group. Upon starting assigned treatments, participants will then return for study visits every 2 weeks to report any possible side effects and to complete standard psychiatric assessment tests. All of these study visits will take approximately 1 hour, except the last, which will take 2 hours. In addition to the psychiatric assessment and review of side effects, the final study visit will also include a physical exam and blood collection.

• Dietary Supplement: EPA omega-3 fatty acid
• Dietary Supplement: DHA omega-3 fatty acid
• Dietary Supplement: Placebo comparator

• Experimental: Participants will take EPA
• Experimental: Participants will take DHA
• Placebo Comparator: Participants will take placebo

Inclusion Criteria:

• Meets DSM-IV diagnostic criteria for major depressive disorder
• A Clinical Global Impression-Severity (CGI-S) score greater than 3
• A Baseline Hamilton-D-17 (HAM-D-17) (Hamilton, 1960,1967) score of ³ 15
• Willing to use effective forms of contraception

Exclusion Criteria:

• Pregnant
• Suicidal or homicidal
• Serious or unstable medical illness, including cardiovascular, liver, kidney, respiratory, endocrine, neuralgic, or blood disease
• History of seizure disorder
• History of organic mental disorders, substance abuse, schizophrenia, schizoaffective disorder, delusional disorder, bipolar disorder, or other psychotic disorders
• History of inflammatory or auto-immune disorder (e.g., rheumatoid arthritis, multiple sclerosis, or cancer
• History of multiple adverse drug reactions or an allergy to the study drugs
• Mood-congruent or mood-incongruent psychotic features
• Current use of other psychotropic drugs
• Clinical or laboratory evidence of hypothyroidism
• Failed to respond during the course of current major depressive episode to at least one adequate antidepressant trial, defined as 6 weeks or more of treatment with 40 mg/day of citalopram (or its antidepressant equivalent)
• Received electroconvulsive therapy (ECT) within 6 months of study entry
• Currently taking supplements enriched with omega-3 fatty acids (e.g., flax seed oil) or has taken at least 1 g/day of omega-3 fatty acids
• Consuming a diet that contains more than 3g/day of omega-3 fatty acids at study entry
• Taking anticoagulants or history of a bleeding disorder
• Patients who are currently in psychotherapy that was initiated within 90 days prior to the study screening visit.
• Current infection
• Use of systematic corticosteroid or steroid antagonists or other immunosuppressant agents (e.g., cyclosporine, interferon)
• Smokes more than 10 cigarettes per day
• Taking a vitamin E supplement greater than 400 IU