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On Jun 23, 6:36*pm, TheBlackBo...@webtv.net (K R) wrote:
> Thanks Vauxall for the information...I will check it out on google.
>
> Kenny http://ajp.psychiatryonline.org/cgi/...full/160/1/188
Omega-3 Fatty Acid for Schizophrenia
DAVID F. HORROBIN, D.Phil., B.M., B.Ch.
Stirling, Scotland
To the Editor: The failure of ethyl eicosapentaenoic acid (EPA)
(omega-3 fatty acid) to produce improvement over placebo in patients
with chronic schizophrenia treated with standard drugs in a study by
Wayne S. Fenton, M.D., and colleagues (1) has several possible
explanations. First, ethyl EPA may have no beneficial effect. This may
be a premature conclusion since it is unlikely that any standard drug
would show benefit in a trial with this add-on design.
Second, ethyl EPA may have no beneficial effects in patients with a
long history of schizophrenia who are presumably taking optimal doses
of standard antischizophrenia drugs. The best results in previous
studies (2–4), two of which were randomized and placebo controlled,
were in patients with a short illness history who were not receiving
standard drugs. Neuroleptics may reduce or block response to ethyl
EPA. However, Emsley et al. (5) recently reported a robust beneficial
effect of ethyl EPA on both schizophrenic symptoms and tardive
dyskinesia in a placebo-controlled trial in patients with chronic
illness.
A third possibility is that the dose was wrong. Previous studies have
used 1–2 g/day rather than the 3 g/day used by Dr. Fenton et al. (1).
We conducted a dose-ranging add-on study of schizophrenia patients in
which placebo was compared with 1 g/day, 2 g/day, or 4 g/day of ethyl
EPA (6). The best results were achieved at the 2-g/day dose, which
produced an increase in red cell EPA without any decrease in red cell
arachidonic acid. At 4 g/day, there was no beneficial effect, and the
increase in red cell EPA was accompanied by a substantial decrease in
arachidonic acid, a fatty acid that plays a central role in many
neuronal signal transduction systems (7). A similar dose-ranging study
in depression (8) also showed a bell-shaped dose-response curve, with
a strong beneficial effect at an ethyl EPA dose of 1 g/day and smaller
effects at higher doses. The large decrease in the arachidonic acid/
EPA ratio reported by Dr. Fenton et al. suggests that the ethyl EPA
dose may have been too high because it depleted arachidonic acid.
Fourth, through the informed consent process, patients may have become
knowledgeable about the beneficial effects of EPA and changed their
diet by consuming EPA-rich foods. In the placebo group, the
arachidonic acid/EPA ratio fell by 4.0 points during the study. This
is a large decrease, indicative of a substantial change in diet. In
our dose-ranging study, we observed a similar decrease in the
arachidonic acid/EPA ratio (–4.2) in the group of patients given 1 g/
day of ethyl EPA (6). The original data of Dr. Fenton et al. (1) do
show that red cell EPA levels rose significantly (p<0.05) in the
placebo group. The placebo patients may therefore have increased their
EPA intake by a suboptimal but still beneficial level, while the
actively treated patients may have received too much. This may explain
why both groups improved.
The study’s failure may have been due to a combination of an
insensitive trial design, a blocking effect of standard drugs, too
high a dose of ethyl EPA in the active group, and a dietary increase
in EPA in the placebo group. Further studies are required,
particularly with lower doses of ethyl EPA in otherwise untreated
patients, before any firm conclusions can be drawn. Such studies are
important because ethyl EPA is so well tolerated. Of 43 patients
receiving ethyl EPA, only six (14%) dropped out during the 16-week
study—none because of side effects. In the dose-ranging study of
depression (8), only 12% of the patients taking any ethyl EPA dropped
out, while in the dose-ranging schizophrenia study (6), only 11%
dropped out. These dropout rates are much lower than those seen with
standard antidepressant or antischizophrenia drugs. Even a modest
beneficial effect would be valuable if produced by such a safe drug.
References
Fenton WS, Dickerson F, Boronow J, Hibbeln JR, Knable M: A placebo-
controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid)
supplementation for residual symptoms and cognitive impairment in
schizophrenia. Am J Psychiatry 2001; 158:2071-2074[Abstract/Free Full
Text]
Puri BK, Richardson AJ: Sustained remission of positive and negative
symptoms of schizophrenia after treatment with eicosapentaenoic acid
(letter). Arch Gen Psychiatry 1998; 55:188-189[Free Full Text]
Peet M, Brind J, Ramchand CN, Shah S, Vankar GK: Two double-blind
placebo-controlled pilot studies of eicosapentaenoic acid in the
treatment of schizophrenia. Schizophr Res 2001; 49:243-251[CrossRef]
[Medline]
Su KP, Shen WW, Huang SY: Omega-3 fatty acids as a psychotherapeutic
agent for a pregnant schizophrenic patient. Eur Neuropsychopharmacol
2001; 11:295-299[CrossRef][Medline]
Emsley R, Myburgh C, Oosthuizer P, van Regsburg SJ: Randomized placebo-
controlled study of ethyl-eicosapentaeroic acid as supplemental
treatment in schizophrenia. Am J. Psychiatry 2000; 159:1596-1598
Peet M, Horrobin DF (E-E Multicentre Study Group): A dose-ranging
exploratory study of the effects of ethyl-eicosapentaenoate in
patients with persistent schizophrenic symptoms. J Psychiatr Res 2002;
36:7-18[CrossRef][Medline]
Horrobin DF: The membrane phospholipid hypothesis as a biochemical
basis for the neurodevelopmental concept of schizophrenia. Schizophr
Res 1998; 30:193-208[CrossRef][Medline]
Peet M, Horrobin DF: A dose-ranging study of the effects of ethyl-
eicosapentaenoate in patients with ongoing depression in spite of
apparently adequate treatment with standard drugs. Arch Gen Psychiatry
2002; 59:913-919[Abstract/Free Full Text]
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