The purpose of this study is to determine whether omega-3 polyunsaturated fatty acids are effective as a monotherapy for depression.

The study will be a 6 week, parallel-group, double-blind randomized controlled trial of the efficacy of Omega-3 as a monotherapy for depression. People aged 21-65 who have major depression but are not currently on an antidepressant or planning to take an antidepressant in the next 14 weeks will be recruited. Participants will be randomly allocated to receive Omega-3 (fish oil) or placebo (paraffin oil) for 6 weeks. Participants will be followed up weekly and will be asked to rate their mood daily for the 6 week study period. Blood samples will be taken pre and post treatment to measure change in omega-3 levels. At the end of 6 weeks all participants will receive a further 8 weeks supply of omega-3.

Inclusion Criteria:

• Must meet DSM IV criteria for non-psychotic major depression lasting at least 6 weeks or dysthymia.
• Must be under the care of a mental health practitioner.
• Must be able to give informed consent.
• Must be able to attend the Black Dog Institute.

Exclusion Criteria:

• Unsuccessful treatment with more than 2 antidepressant medications (at therapeutically adequate doses and duration.
• History of psychosis or mania/hypomania or personality disorder.
• Non-English speaking or otherwise unable to provide historical information.
• Having taken Omega-3 dietary supplements in the last 3 months.
• Taking antidepressant medication for depression.
• History of allergy to n-3 PUFA supplements, finfish or shellfish.
• Pregnancy, breast feeding or planning to become pregnant during course of study.
• Post-natal depression.
• Current drug or alcohol abuse or dependence or history of abuse or dependence over the last 12 months.
• Unstable thyroid function
• Hepatic or renal impairment or other medical conditions that may interfere with the absorption and metabolism of omega-3 polyunsaturated fatty acids.
• Coagulopathy or anticoagulant treatment.
• Patients who, in the investigator's judgment pose a current serious suicidal or other safety risk, or patients who are not likely to be able to comply with the study protocol.