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Studies on Omega-3 for Depression
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- Fontani G, et al. University of Siena,
Italy. Cognitive and physiological
effects of Omega-3 polyunsaturated fatty acid supplementation in healthy
subjects. Eur J Clin Invest. 2005; 35(11): 691-699.
Abstract: Background: It has been reported
that Omega-3 fatty acids may play a role in nervous system activity and that
they improve cognitive development and reference memory-related learning,
increase neuroplasticity of nerve membranes, contribute to synaptogenesis and
are involved in synaptic transmission. The aim of this study was to examine the
effects of Omega-3 supplementation on some cognitive and physiological
parameters in healthy subjects. Materials and methods: Subjects were tested at
the beginning of the experiment and after 35 days. In this period they
were supplemented with Omega-3 polyunsaturated fatty acids. A group was
supplemented with olive oil (placebo). Tests involving different types of
attention were used, i.e. Alert, Go/No-Go, Choice and Sustained Attention. For
each test, the reaction time, the event-related potentials by
electroencephalogram (EEG) and the electromyography (EMG) of the forefinger
flexor muscle were recorded. The Profile of Mood States test (POMS) was also
administered. Results: Blood analyses showed that after Omega-3 supplementation
the arachidonic acid/eicosapentaenoic acid ratio (AA/EPA) was strongly reduced.
The mood profile was improved after Omega-3 with increased vigour and reduced
anger, anxiety and depression states. This was associated with an effect on
reactivity with a reduction of reaction time in the Go/No-Go and Sustained
Attention tests. The latency of EMG activation was concomitantly reduced in the
same tests plus Choice. An EEG frequency shift towards the theta and alpha band
were recorded in all the tests after Omega-3. Conclusions: Omega-3
supplementation is associated with an improvement of attentional and
physiological functions, particularly those involving complex cortical
processing. These findings are discussed in terms of the influence of Omega-3
on the central nervous system.
- Frais AT. Depression
and the causal role of specific memory system degenerations: Link may be
supported by reported therapeutic benefits of Omega 3 fatty acids. Medical Hypotheses. 2007; 69(1): 67-69.
Abstract: It is well documented that depressed patients, as a result of
their illness, often experience some difficulties with their memory. This hypothesis suggests a vice-versa; that it is a gradual
impairment and ultimate failure of specific memory systems that may underpin
the onset and continuation of a depressive illness. So particular memory
systems of the brain may have a greater role to play in clinical depression and
associated anxiety than is generally recognised. A common feature of electroconvulsive therapy (ECT) is that it
affects patients' short-term memory adversely. However, in line with the
hypothesis, it is suggested that the mechanism of action of successful ECT
treatment is that it facilitates the repair and reactivation of particular
memory systems. One link that has some bearing on this hypothesis is that of Omega
3 fish oil. It has in some cases been observed to aid recovery of depression
and possibly prevent relapse. It has been shown to improve memory.
- Maes M, et al.
Lowered omega-3 polyunsaturated fatty acids in serum phospholipids and cholesteryl
esters of depressed patients. Psychiatry
Research. 1999; 85: 275-291.
Abstract: Depression is associated with a lowered degree of esterification
of serum cholesterol, an increased C20:4ω6/C20:5ω3 ratio and decreases in ω3
fractions in fatty acids (FAs) or in the red blood cell membrane. The aims of
the present study were to examine: (i) serum phospholipid and cholesteryl ester
compositions of individual saturated fatty acids (SFAs), monounsaturated FAs
(MUFAs) and polyunsaturated FAs (PUFAs) in major depressed patients vs. healthy
volunteers; (ii) the relationships between the above FAs and lowered serum zinc
(Zn), a marker of the inflammatory response in depression; and (iii) the
effects of subchronic treatment with antidepressants on FAs in depression. The
composition of the FAs was determined by means of thin layer chromatography in
conjunction with gas chromatography. Lipid concentrations were assayed by
enzymatic colorimetric methods. The oxidative potential index (OPI) of FAs was
computed in 34 major depressed inpatients and 14 normal volunteers. Major
depression was associated with: increased MUFA and C22:5ω3 proportions and
increased C20:4ω6/C20:5ω3 and C22:5ω6/C22:6ω3 ratios; lower C22:4ω6, C20:5ω3
and C22:5ω3 fractions in phospholipids; lower C18:3ω3, C20:5ω3 and total (Σ)ω3
FAs, and higher C20:4ω6/C20:5ω3 and Σω6/Σω3 ratios in cholesteryl esters; lower
serum concentrations of phospholipids and cholesteryl esters; and a decreased
OPI. In depression, there were significant and positive correlations between
serum Zn and C20:5ω3 and C22:6ω3 fractions in phospholipids; and significant
inverse correlations between serum Zn and the Σω6/Σω3, C20:4ω6/C20:5ω3, and
C22:5ω6/C22:6ω3 ratios in phospholipids. There was no significant effect of
antidepressive treatment on any of the FAs. The results show that, in major
depression, there is a deficiency of ω3 PUFAs and a compensatory increase in
MUFAs and C22:5ω6 in phospholipids. The results suggest that: (i) there is an
abnormal metabolism of ω3 PUFAs in depression; (ii) the FA alterations in
depression are related to the inflammatory response in that illness; and (iii)
the disorders may persist despite successful antidepressant treatment.
- Malcolm Peet, MB, ChB, FRCPsych; David F.
Horrobin, DPhil, BM, BCh. A
Dose-Ranging Study of the Effects of Ethyl-Eicosapentaenoate in Patients With
Ongoing Depression Despite Apparently Adequate Treatment With Standard Drugs. Arch
Gen Psychiatry. 2002;59:913-919.
Abstract: Background In depressed patients, low blood levels
of eicosapentaenoic acid are seen. We tested the antidepressive
effect of ethyl-eicosapentaenoate in these patients. Methods We included 70 patients
with persistant depression despite ongoing treatment with an
adequate dose of a standard antidepressant. Patients were randomized
on a double-blind basis to placebo or ethyl-eicosapentaenoate at
dosages of 1, 2, or 4 g/d for 12 weeks in addition to unchanged
background medication. Patients underwent assessment using the
17-item Hamilton Depression Rating Scale, the Montgomery-Asberg
Depression Rating Scale, and the Beck Depression Inventory. Results Forty-six (88%) of 52
patients receiving ethyl-eicosapentaenoate and 14 (78%) of 18
patients receiving placebo completed the 12-week study with no
serious adverse events. The 1-g/d group showed a significantly
better outcome than the placebo group on all 3 rating scales. In the
intention-to-treat group, 5 (29%) of 17 patients receiving placebo
and 9 (53%) of 17 patients receiving 1 g/d of
ethyl-eicosapentaenoate achieved a 50% reduction on the Hamilton
Depression Rating Scale score. In the per-protocol group, the
corresponding figures were 3 (25%) of 12 patients for placebo and 9
(69%) of 13 patients for the 1-g/d group. The 2-g/d group showed
little evidence of efficacy, whereas the 4-g/d group showed
nonsignificant trends toward improvement. All of the individual
items on all 3 rating scales improved with the 1-g/d dosage of
ethyl-eicosapentaenoate vs placebo, with strong beneficial effects
on items rating depression, anxiety, sleep, lassitude, libido, and
suicidality. Conclusion Treatment with
ethyl-eicosapentaenoate at a dosage of 1 g/d was effective in
treating depression in patients who remained depressed despite
adequate standard therapy.
- Marangell LB, Martinez JM, Zboyan HA, Kertz B, Kim HF,
Puryear LJ. A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic
acid in the treatment of major depression. Am J Psychiatry. 2003 May; 160(5): 996-998.
Abstract: OBJECTIVE: This study was an evaluation of the omega-3
fatty acid docosahexaenoic acid (DHA) for the treatment of major
depression. METHOD: Thirty-six depressed patients were
randomly assigned to receive DHA, 2 g/day, or placebo for 6 weeks.
Response was defined a priori as a
50% reduction in the score on the Montgomery-Åsberg Depression
Rating Scale. Thirty-five participants were evaluable; 18 received
DHA, and 17 received placebo. RESULTS: Response rates were
27.8% in the DHA group and 23.5% in the placebo group. The
difference in response rates between groups did not reach statistical
significance. CONCLUSIONS: This trial failed to show a
significant effect of DHA monotherapy in subjects with major
depression.
- Nemets B, Stahl Z, Belmaker RH. Addition of omega-3 fatty acid to maintenance medication treatment for
recurrent unipolar depressive disorder. Am J
Psychiatry. 2002 Mar; 159(3): 77-79.
Abstract: OBJECTIVE: Studies have reported that
countries with high rates of fish oil consumption have low rates of
depressive disorder. The authors studied a specific omega-3 fatty
acid, the ethyl ester of eicosapentaenoic acid (E-EPA), as an
adjunct to treatment for depressive episodes occurring in patients
with recurrent unipolar depressive disorder who were receiving
maintenance antidepressant therapy. METHOD: Twenty patients
with a current diagnosis of major depressive disorder participated
in a 4-week, parallel-group, double-blind addition of either placebo
or E-EPA to ongoing antidepressant therapy. Seventeen of the
patients were women, and three were men. RESULTS: Highly
significant benefits of the addition of the omega-3 fatty acid
compared with placebo were found by week 3 of treatment. CONCLUSIONS:
It is not possible to distinguish whether E-EPA augments
antidepressant action in the manner of lithium or has independent
antidepressant properties of its own.
- Peet M. Essential fatty acids: theoretical aspects and
treatment implications for schizophrenia and depression. Advances in psychiatric treatment . The
Royal College of Psychiatrists. 2002; 8: 223-229.
- Peet M, et al.
Depletion of omega-3 fatty acid levels in red blood cell membranes of
depressive patients. Biological
Psychiatry. 1998; 43: 315-319.
Abstract: Background: It has been hypothesized that depletion of cell
membrane n3 polyunsaturated fatty acids (PUFA), particularly docosahexanoic
acid (DHA), may be of etiological importance in depression. Methods: We measured the fatty acid composition of phospholipid in
cell membranes from red blood cells (RBC) of 15 depressive patients and 15
healthy control subjects. Results: Depressive patients showed significant depletions of
total n3 PUFA and particularly DHA. Incubation of RBC from control subjects
with hydrogen peroxide abolished all significant differences between patients
and controls. Conclusions: These findings suggest that RBC membranes in
depressive patients show evidence of oxidative damage. Possible
interpretations, and implications for the etiology and treatment of depression,
are discussed.
- Stoll AL. The Omega 3 connection. Free Press, New York
(2001).
- Peet M, Horrobin DF. A dose-ranging study of the effects of
ethyl-eicosapentaenoate in patients with ongoing depression despite apparently
adequate treatment with standard drugs. Arch Gen Psychiatr. 2002;
59: 913-919.
Abstract: Background In depressed patients, low blood levels
of eicosapentaenoic acid are seen. We tested the antidepressive
effect of ethyl-eicosapentaenoate in these patients. Methods We included 70 patients
with persistant depression despite ongoing treatment with an
adequate dose of a standard antidepressant. Patients were randomized
on a double-blind basis to placebo or ethyl-eicosapentaenoate at
dosages of 1, 2, or 4 g/d for 12 weeks in addition to unchanged
background medication. Patients underwent assessment using the
17-item Hamilton Depression Rating Scale, the Montgomery-Asberg
Depression Rating Scale, and the Beck Depression Inventory. Results Forty-six (88%) of 52
patients receiving ethyl-eicosapentaenoate and 14 (78%) of 18
patients receiving placebo completed the 12-week study with no
serious adverse events. The 1-g/d group showed a significantly
better outcome than the placebo group on all 3 rating scales. In the
intention-to-treat group, 5 (29%) of 17 patients receiving placebo
and 9 (53%) of 17 patients receiving 1 g/d of
ethyl-eicosapentaenoate achieved a 50% reduction on the Hamilton
Depression Rating Scale score. In the per-protocol group, the
corresponding figures were 3 (25%) of 12 patients for placebo and 9
(69%) of 13 patients for the 1-g/d group. The 2-g/d group showed
little evidence of efficacy, whereas the 4-g/d group showed
nonsignificant trends toward improvement. All of the individual
items on all 3 rating scales improved with the 1-g/d dosage of
ethyl-eicosapentaenoate vs placebo, with strong beneficial effects
on items rating depression, anxiety, sleep, lassitude, libido, and
suicidality. Conclusion Treatment with
ethyl-eicosapentaenoate at a dosage of 1 g/d was effective in
treating depression in patients who remained depressed despite
adequate standard therapy.
- Su KP, Huang SY, Chiu CC, Shen WW. Omega-3 fatty acids in major depressive disorder. A preliminary
double-blind, placebo-controlled trial. Eur
Neuropsychopharmacol. 2003 Aug; 13(4): 267-271.
Abstract: Patients with depression have been extensively reported to be
associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs),
including significantly low eicosapentaenoic acid and docosahexaenoic acid in
cell tissue contents (red blood cell membrane, plasma, etc.) and dietary
intake. However, more evidence is needed to support its relation. In this
study, we conducted an 8-week, double-blind, placebo-controlled trial,
comparing omega-3 PUFAs (9.6 g/day) with placebo, on the top of the usual treatment,
in 28 patients with major depressive disorder. Patients in the omega-3 PUFA
group had a significantly decreased score on the 21-item Hamilton Rating Scale
for Depression than those in the placebo group (P<0.001). From the
preliminary findings in this study, omega-3 PUFAs could improve the short-term
course of illness and were well tolerated in patients with major depressive
disorder.
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