N-3 Polyunsaturated Fatty Acids in the Prevention and Treatment for IFN-induced Depression

Study Overview
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Brief Summary
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The first part is a double-blind placebo-controlled trial to identify the effects of omega-3 polyunsaturated fatty acids (PUFAs) in prevention of IFN-induced depression. The second part is a double-blind trial to identify the antidepressant effects of omega-3 PUFAs in patients with IFN-induced depression.

Detailed Description
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We have done a preliminary analysis in 63 HCV patients receiving IFN-α therapy enrolled in our current NSC project (NSC95-2320-B-039-037-MY3) and found that patients who later developed IFN-α-induced depression (case group, 21/63) had lower PUFA levels before starting IFN-α therapy than control group (p=0.024). In addition, there was a trend for a negative correlation (r=-0.224; p=0.078) between baseline DHA levels and the highest scores of BDI during IFN therapy in the whole group. These findings indicate that n-3 PUFAs might play a protective factor. This 3-year proposal is divided into 2 clinical studies. In study 1, we aim to test the prophylactic effect of n-3 PUFAs (EPA: 3.5 g/d and DHA: 1.75 g/d versus placebo: high oleic oil) for IFN-α-induced sickness behaviour and depressive symptoms, in a two-week, double-blind, placebo-controlled trial of 152 patients with HCV starting IFN-α therapy. In study 2, we will test the antidepressant effect of n-3 PUFAs (EPA: 3.5 g/d and DHA: 1.75 g/d versus placebo: high oleic oil) on IFN-α-induced depression during IFN-α therapy, in an eight-week, double-blind, placebo-controlled trial in 80 HCV patients who have already developed depression.

Official Title
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N-3 Polyunsaturated Fatty Acids in the Prevention and Treatment for IFN-induced Depression

Conditions
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Major Depressive Episode

Intervention / Treatment
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* Dietary Supplement: Omega-3 fatty acids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible participants will be adult patients with chronic HCV, assessed by hepatologists and then referred for IFN-α therapy and have capacity and willingness to give written informed consent Exclusion Criteria: Patients will be excluded if they have major depressive episode at assessment Any history of pre-existing psychotic disorders (e.g. schizophrenia or bipolar disorder) Alcohol or drug dependence within one year before entry into the study Seizure disorders and evidence of any unstable substantial coexisting medical conditions (e.g. cardiovascular, endocrine, haematological, renal, or neurological diseases)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EPA 3.5 g/day<br> | Dietary Supplement: Omega-3 fatty acids<br>* A daily treatment of 5 identical capsules of EPA (3.5 g/d), DHA (1.75 g/d) or placebo (high oleic oil), in single or divided administration for 2 (Study 1) or 8 weeks (Study 2)<br>* Other names: Omega-3 PUFAs or fish oil;|
| Placebo Comparator: Placebo capsules<br>oleic oil | Dietary Supplement: Omega-3 fatty acids<br>* A daily treatment of 5 identical capsules of EPA (3.5 g/d), DHA (1.75 g/d) or placebo (high oleic oil), in single or divided administration for 2 (Study 1) or 8 weeks (Study 2)<br>* Other names: Omega-3 PUFAs or fish oil;|
| Experimental: DHA 1.75 g/day<br>DHA 1.75 g/day | Dietary Supplement: Omega-3 fatty acids<br>* A daily treatment of 5 identical capsules of EPA (3.5 g/d), DHA (1.75 g/d) or placebo (high oleic oil), in single or divided administration for 2 (Study 1) or 8 weeks (Study 2)<br>* Other names: Omega-3 PUFAs or fish oil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with major depressive episode (for Study 1); Changes in Hamilton Depression Rating Scale (HDRS) (for Study 2) |  | Weeks 0 to 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Hamilton Depression Rating Scale (HDRS) (for Study 1); Response and remission rates (for Study 2) |  | Weeks 0 to 24 |