Omega-3 fatty acids in the prevention of
interferon-alpha-induced depression
Kuan-Pin Su, M.D., Ph.D.a, c, e, , , Hsueh-Chou Lai, M.D.b, Hui-Ting Yang, Ph.D.d, Wen-Pang
Su, M.D.b, Cheng-Yuan Peng, M.D., Ph.D.b, Jane Pei-Chen Chang, M.D., M.S.a, Hui-Chih
Chang, M.Sc.a, Carmine M. Pariante, M.D., Ph.D, FRCPsych.e,
presentation by Qiujing Hu
introduction/background
study the benifits of omega 3 fatty acids for the prevention and delay of interferon
therapy of hepatitis C induced depression
 what is hepatitis C?
Hepatitis C is an infectious disease affecting primarily the liver, caused by the hepatitis C virus (HCV).
 treatment
Interferon (IFN)-α
IFNs belong to the large class of glycoproteins known as cytokines. Interferons are named after their ability to "interfere"
with viral replication within host cells.
 side effects
interferon therapy is highly associated with depression. treatments with antidepressants might expose patients to adverse
effects, therefore, alternative of antidepressants is needed.
 treatment of side effect
Omega-3 polyunsaturated fatty acids (PUFAs) has been found to be a
safe and effective treatment of depression, and is workded through an anti-inflammatory action.
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Rationale
the purpose of this papaer is to studies the effects of
omega-3 PUFAs, EPA and DHA to prevent IFN alpha
induced depression
Hypothesis: the effects of the omega-3 PUFAs, EPA and DHA, against
placebo can prevent IFN-α-induced depression.
methods
 Doule-blind, placebo-controlled trial
 3 tials: comparing EPA; DHA or placebo
 152 randomized paitient were given treatment for 2 weeks and were
followed throughout the 24 weeks of IFN-α treatment, and these
paitients are included in the analysis
 The recruited participants were evaluated at weeks –2 (when omega3 fatty acid intervention started), and every 2 week when the
intervention stopped and therapy started, to monitor the occurrence
of major depressive episode.
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results
incident rates of IFN-induced depression
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results
 Survival curves (Kaplan-Meier estimates) of cumulative incidences of IFNinduced depression of 152 patients with hepatitis C viral infection who
were pre-treated with EPA (n=50), DHA (n=51) or placebo (n=51) for 2
weeks before a 24-week IFN-α therapy.
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results
 In the overall sample, a total of 34 patients (22%) developed IFN-αinduced depression at some point during the 24-week therapy, while 118
(78%) patients did not develop IFN-α-induced depression. At week -2
(before the intervention), subjects who later developed IFN-α-induced
depression had lower baseline EPA levels than those who did not , but not
DHA levels . However, at week 0, there were no significant differences in
EPA or DHA levels between subjects who did or did not develop IFNalpha-induced depression.
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discussion
 overall findings:
The main finding is that EPA pre-treatment significantly decreased the
incidence of IFN-α-induced depression in HCV patients.
both EPA and DHA pre-treatment significantly delayed the onset of IFN-αinduced depression as compared to placebo pre-treatment.
 EPA can be metabolised into DHA
 These results therefore indicate EPA and DHA work together to lower
depression symptoms.
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discussion
 why the pro-inflammatory cytokines promotes depression
 IDO pathway produces depressive metabolites
. EPA has numerous anti-inflammatory properties:
prevents membrane AA formation
inhibits COX2 enzyme activity
reduces PGE2 synthesis
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conclusion
 In conclusion, EPA was beneficial for the prevention of IFN-α-induced
depression, while DHA had only modest effects on delaying the onset.
The data suggest that EPA or EPA/DHA combination is the best
preventive strategy in this group of patients, and potentially a suitable
strategy for the wider pool of patients with depression associated with
inflammation.
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