Taking fish oil boosts the effect of antidepressant medicines

Omega-3 fatty acids for mood disorders – Harvard Health Blog – Harvard Health Publishing

Taking fish oil boosts the effect of antidepressant medicines

Omega-3 fatty acids are found primarily in fish oil and certain marine algae.

Because depression appears less common in nations where people eat large amounts of fish, scientists have investigated whether fish oils may prevent and/or treat depression and other mood disorders.

Two omega-3 fatty acids — eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) — are thought to have the most potential to benefit people with mood disorders.

How might omega-3s improve depression?

Different mechanisms of action have been proposed. For example, omega-3s can easily travel through the brain cell membrane and interact with mood-related molecules inside the brain. They also have anti-inflammatory actions that may help relieve depression.

More than 30 clinical trials have tested different omega-3 preparations in people with depression. Most studies have used omega-3s as add-on therapy for people who are taking prescription antidepressants with limited or no benefit.

Fewer studies have examined omega-3 therapy alone. Clinical trials typically use EPA alone or a combination of EPA plus DHA, at doses from 0.5 to 1 gram per day to 6 to 10 grams per day.

To give some perspective, 1 gram per day would correspond to eating three salmon meals per week.

Meta-analyses (research that combines and analyzes results of multiple studies) generally suggest that the omega-3s are effective, but the findings are not unanimous because of variability between doses, ratios of EPA to DHA, and other study design issues.

The most effective preparations appear to have at least 60% EPA relative to DHA. While DHA is thought to be less effective as an antidepressant, it may have protective effects against suicide.

Recent work at Massachusetts General Hospital and Emory University suggests that depressed individuals who are overweight and have elevated inflammatory activity may be particularly good candidates for EPA treatment.

Children and adolescents with depression may also benefit from omega-3 supplementation. At Harvard, there is a large study underway examining whether omega-3 supplementation (alone or in combination with vitamin D) can prevent depression in healthy older adults.

Omega-3s for other mental health conditions

Omega-3s have been studied in various mood disorders, such as postpartum depression, with some promising results. In bipolar disorder (manic depression), the omega-3s may be most effective for the depressed phase rather than the manic phase of the illness.

The omega-3s have also been proposed to alleviate or prevent other psychiatric conditions including schizophrenia, borderline personality disorder, obsessive compulsive disorder, and attention deficit disorder.

However, there is still not enough evidence to recommend the omega-3s in these conditions.

What dose of omega-3s is beneficial?

Doses for depression range from less than 1 g/day to 10 g/day, but most studies use doses between 1 and 2 g/day. In my practice, I recommend 1 to 2 g/day of an EPA+DHA combination, with at least 60% EPA, for major depression.

I am more cautious in patients with bipolar depression, because the omega-3s may bring on mania, as can most antidepressants.

In these individuals, I recommend using omega-3 cautiously, and preferably in combination with a prescription mood stabilizer.

Side effects and other safety considerations

Omega-3s are generally safe and well tolerated. Stomach upset and “fishy taste” have been the most common complaints, but they are less frequent now thanks to manufacturing methods that reduce impurities.

Past concerns about omega-3s increasing the risk of bleeding have been largely disproven, but caution is still advised in people taking blood thinners or who are about to undergo surgery. As mentioned, caution is needed in people with bipolar disorder to prevent cycling to mania.

Because omega-3s are important to brain development, and pregnancy depletes omega-3 in expectant mothers, supplementation should theoretically benefit pregnant women and their children.

Fish consumption in pregnancy is supported by the FDA, but because we do not have long-term data on safety or optimal dosing of omega-3s in pregnancy, expectant mothers should consider omega-3 supplements judiciously.

The bottom line on omega-3s and mental health

Omega-3 fatty acids are promising natural treatments for mood disorders, but we need more research about how they work, how effective they really are, and their long-term safety before we can make conclusive recommendations for people managing mental health conditions or who wish to improve mood.

Dr. Mischoulon will present “Omega-3 Fatty Acids for Mood Disorders and Other Psychiatric Conditions” at the Osher Center for Integrative Medicine Grand Rounds at Brigham and Women’s Hospital on August 7th, 2018, from 8 to 9 AM. Members of the public are welcome to attend his talk.


The VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention (VITAL-DEP): Rationale and design of a large-scale ancillary study evaluating vitamin D and marine omega-3 fatty acid supplements for prevention of late-life depression. Contemporary Clinical Trials, May 2018.

Source: https://www.health.harvard.edu/blog/omega-3-fatty-acids-for-mood-disorders-2018080314414

Vitamin D, fish oil and folates may enhance antidepressants

Taking fish oil boosts the effect of antidepressant medicines

“Do antidepressants work better when taken with supplements?,” the Mail Online asks.

A new review of existing evidence suggests that, “Omega-3 fish oils, certain amino acids, folate and vitamin D” may boost the beneficial effect of antidepressants, the Mail says.

There was also tentative evidence that S-Adenosyl methionine (SAMe) – a type of amino acid supplement popular in some countries – may boost the effects of antidepressants.

Researchers from Melbourne, Australia, reviewed the evidence about combining antidepressant treatment for depression with “nutraceuticals” – nutrient-based supplements produced to pharmaceutical standards. This means that consumers can be confident about information relating to important issues such as dosage and ingredients. 

The researchers looked at 40 studies, of varying quality, to pool the results where possible and draw conclusions. They found that omega-3 supplements (usually derived from fish oil) had a significant effect, but there were varying results for other nutraceuticals studied.

In some cases, only one or two small studies had been published, making it hard to rely on the results. The researchers also found evidence that more positive studies than expected had been published, suggesting that some negative studies had not been published (publication bias).

The researchers say they have shown that EPA-rich omega-3 oil “may be recommended” as an additional treatment for depression, alongside antidepressants. But they caution that people taking antidepressants should talk to their doctors before starting any supplements.  

Where did the story come from?

The study was carried out by researchers from the University of Melbourne, Swinburne University of Technology, Deakin University, the National Centre of Excellence in Youth Mental Health, and the Florey Institute for Neuroscience and Mental Health, all in Australia, and Harvard Medical School in the US. Information on funding was not provided in the study. 

The study was published in the peer-reviewed journal The American Journal of Psychiatry. Six of the seven authors reported financial interests in the field, mainly research funding and payments for speaking and writing about pharmaceuticals and nutraceuticals.

The Mail Online reported the results of the study uncritically, without considering the strength of the evidence for the different nutrients studied. Of the three nutrients named in its headline, the study only found strong evidence for omega-3.

What kind of research was this?

This study was a systematic review, with meta-analyses performed where there was sufficient evidence to do so. The researchers found enough studies to perform meta-analyses for just two nutrients: omega-3 and folic acid.

Meta-analyses are a good way of pooling results of studies, giving an overall view of whether a treatment works. However, systematic reviews and meta-analyses are only as good as the individual trials that go into them.

What did the research involve?

Researchers searched for any studies in English that looked at the effects of adding one of 14 nutrients known to be involved in nerve cell function to antidepressant treatments. They divided them into groups and summarised the results. For nutrients where they had at least two randomised controlled trials (RCTs), they carried out a meta-analysis.

They included open-label studies (where people knew which treatment they were taking) and uncontrolled studies, where they looked at the effect of adding a nutraceutical treatment to an antidepressant for people who had not responded to an antidepressant, without using a placebo for comparison. People in the studies had to have been diagnosed with a major depressive disorder or have ongoing depression.

For most of the nutrients, they summarised the results from the different studies, stating how many showed a positive effect and how many did not. For folic acid and omega-3 oils, they carried out meta-analyses of the mean difference between treatment and placebo, in the change from start to end of the study.

What were the basic results?

The most reliable evidence came from the meta-analyses:


Eight studies, all RCTs containing 20 to 122 people, looked at the effect of omega-3. Six of the eight studies showed a statistically significant reduction in depression scores for the treatment group, compared to the placebo group.

The meta-analysis showed a statistically significant effect size of 0.61 for the difference between the treatment and placebo group (p=0.0009).

It is not possible to interpret how clinically important this effect size is, as there was no information about the actual depression scores in the studies.

Folic acid

Four RCTs looked at the effects of folic acid. Two of them showed a reduction in depression scores for people taking folic acid, but one big study showed no significant effect. The meta-analysis showed no statistically significant effect size.

Other nutrients

Other nutrients which the researchers said showed positive effects included:

  • an amino acid based nutrient called S-adenosylmethionine (SAMe) – three small open-label studies found a positive effect; however, the only RCT found no significant effect
  • methylfolate, a type of folate – three small trials (one open-label) found a positive effect; one larger RCT found no significant effect
  • vitamin D – one RCT and one open-label study, both fairly small, found a positive effect

The other nutrients studied either had only one study looking at them, or mixed results. Evaluation of the meta-analyses showed big differences between the study results, and potential publication bias (where studies are published if they are positive, but not if they are negative).

How did the researchers interpret the results?

The researchers were upbeat about the results, especially for omega-3 oils, which they said could now be recommended for use as an add-on treatment alongside antidepressants, on the basis of their results.

They conclude: “several nutraceuticals may hold a potential clinical application to enhance the antidepressant effect of medications” and that groups issuing guidelines for doctors should consider including nutraceuticals.

However, they admit that good-quality, large RCTs are now needed.


Many people with depression benefit from taking antidepressants, but some either don't find them helpful, or don't completely recover while taking them. A safe and effective way to boost the effects of antidepressants would therefore be useful.

This study is a useful summary of which nutrients have been tested as an add-on to antidepressants, and an overall indication of what the studies found. It shows that, for most of these nutrients, the evidence comes from small studies of varying quality and length, and that we need bigger, better studies to get a true picture of their effects.

For the nutrients where there was sufficient evidence to carry out a meta-analysis, the difficulty is that the way the results are presented makes it hard to tell how much of an effect the nutrients actually had on people's depression.

We don't know whether the difference in the effect of treatment seen with omega-3 supplements amounted to more people getting completely better from depression, or whether some people's depression scores on questionnaires improved a few points, but not enough to make much difference to their quality of life. The researchers describe the effect as “moderate to strong”.

If you are taking antidepressants and feel they are not making much difference, talk to your doctor. Antidepressants take a while to start working properly, so you may need to wait a little longer.

If you've been taking them for a while and they don't help, talk to your GP about trying another type of antidepressant, or a different dose.

If you are interested in taking a supplement alongside your antidepressant, talk to your doctor first.

Finally, it's important to remember that the study was looking at “nutraceuticals” – nutrient-based supplements produced to pharmaceutical standards. If you do decide to try a supplement, make sure it is from a trusted source with a reputation for safety and high quality.

Analysis by Bazian
Edited by NHS Website

Source: https://www.nhs.uk/news/mental-health/vitamin-d-fish-oil-and-folates-may-enhance-antidepressants/

Fish Oil May Make Antidepressants More Effective

Taking fish oil boosts the effect of antidepressant medicines

Finding ways to make antidepressants more effective could help the millions of people who take them for depression. Now early research suggests pairing the medication with certain supplements, including omega-3 fish oil and vitamin D, could be one way to do so.

In the new study published in the American Journal of Psychiatry, researchers looked at what happened when some supplements were paired with antidepressants. They combed 40 clinical trials that tested antidepressants taken in conjunction with omega-3s, vitamin D and zinc—nutritional supplements sometimes used to help treat depression, often called nutraceuticals.

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The researchers found that people who took omega 3s with antidepressants reported fewer depressive symptoms compared to people taking antidepressants alone.

While omega-3s had the most powerful effect, other nutraceuticals also improved the effects of antidepressants, including S-adenosylmethionine, a synthetic form of a compound formed naturally in the body that helps maintain cells and brain chemicals; methylfolate, a form of folate; and vitamin D. Mixed results were seen for zinc, folic acid, vitamin C and the amino acid tryptophan.

Research suggests that the supplements tested in the studies target some of the similar brain processes and pathways as antidepressants. Though recent research has been somewhat mixed, omega-3 supplements have been found to potentially benefit parts of the brain thought to be linked to depression and mood.

“Omega-3 fatty acids appear to exert a range of biological activity which may be beneficial for improving mood,” says study author Jerome Sarris, head of the ARCADIA Mental Health Research Group at the University of Melbourne, in an email. “The question remains whether when combined with medication, a unique beneficial interactive effect is occurring, or whether it is due to two distinct yet complementary mood elevating effects.”

Even though millions of Americans take antidepressants, there’s a lot experts don’t know about the drugs, including how exactly they work and why some people respond to them better than others.

Antidepressants also appear to have a powerful placebo effect; recent data suggests that anywhere from 30-45% of response to an antidepressant is due to the power of placebo.

Figuring out how to make the drugs more effective could help a lot of people.

“I’m cautiously optimistic about the results, which show some positive benefit,” says Dr. Richard Friedman, professor of clinical psychiatry at Weill Cornell Medical College who was not involved with the study.

“There are many methodology concerns about individual studies, small sample sizes. But the results of this study clearly justify more rigorous large randomized clinical trials of nutraceuticals in the treatment of depression.

” Nutraceuticals are largely unregulated, he says, “so quality and purity is a concern.”

The researchers did not turn up major safety issues and found that overall the supplements were well-tolerated; the most commonly reported side effects were constipation, stomach upset and diarrhea.

Still, people should consult with their physician about what supplements and medications to take, they conclude.

the findings, which need to be replicated in larger studies, taking supplements alongside antidepressants may be a low-cost way to improve treatment.

Contact us at editors@time.com.

Source: https://time.com/4306313/fish-oil-omega-antidepressants/

Do Vitamins and Supplements Make Antidepressants More Effective?

Taking fish oil boosts the effect of antidepressant medicines

The multibillion-dollar supplement industry spews many dubious claims, but a new study suggests that some nutritional supplements, including omega-3 fatty acids and vitamin D, may boost the effectiveness of antidepressants. If so, the supplements might help relieve symptoms for the millions of people who don’t immediately respond to these drugs.

The meta-analysis—published Tuesday in the American Journal of Psychiatry—reviewed the results of 40 clinical trials that evaluated the effects of taking nutritional supplements in conjunction with several major classes of antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants. It revealed that four supplements in particular upped the potency of the medications, compared with a placebo.

The researchers, based at Harvard University and the University of Melbourne, found the strongest evidence for an omega-3 fish oil called eicosapentaenoic acid, or EPA.

In general, people with depression who took an antidepressant drug and an omega-3 sourced from fish oil experienced a significant reduction in their symptoms as assessed by the Hamilton Depression Rating Scale, a common measure used by most of the studies in the review.

The same was true, although to a lesser extent, for S-adenosylmethionine, methylfolate (a form of the B vitamin folic acid) and Vitamin D.

A few isolated studies found some benefit from augmenting treatment with creatine, while adding zinc, vitamin C, the amino acid tryptophan and folic acid produced mixed results. The authors deemed all of these supplements relatively safe.

Lead study author Jerome Sarris of the University of Melbourne’s ARCADIA Mental Health Research Group notes that a large percentage of people with depression do not fully respond during one or two trials of an antidepressant.

By some estimates, two-thirds don’t respond to the first antidepressant they try and a third fail to get better after several treatment attempts.

“The implications are that clinicians and the public can consider [adding] therapeutic doses of nutrients such as omega-3s as a potential low-cost approach to reducing depression in people who are non-responsive to antidepressants,” he says.  

Sarris and his colleagues speculate that the supplements may enhance the efficacy of antidepressants in various ways, perhaps directly by altering neurotransmitter activity or indirectly by reducing inflammation, known to contribute to depression.

Leading nutritional psychiatry researcher Felice N.

Jacka of Deakin University and the University of Melbourne explains that conditions depression can trigger a cascade of physical concerns that certain supplements, when combined with accepted antidepressant therapies, could help mitigate.

“Serious illnesses such as major depression can result in increased inflammation and oxidative stress, which can in turn result in nutritional deficiencies and a depletion of essential fatty acids,” she notes. “Nutrients form the substrate of the essential biological processes of the body and brain, so ensuring that nutrient levels are adequate in patients suffering from any serious illnesses is important.”

Doctors and scientists often come down hard on nutritional supplementation.

There is little to no scientific evidence backing many of the products crowding the shelves at health food stores and pushed by celebrity doctors.

In fact, many come in mega-doses associated with serious side effects. And countless manufacturers produce these supplements, many with no standardized processes and varying degrees of quality control.

Indeed, the supplement industry exists largely outside of any oversight by the Food and Drug Administration (FDA). In December last year, the FDA announced the formation of a new Office of Dietary Supplement Programs to help tighten regulation, but for now when it comes to supplements, consumers often don’t know what they are getting.

Sarris acknowledges that supplements can differ greatly in quality and that his results should be approached with caution. “We're not telling people to rush out and buy buckets of supplements,” he wrote in a press release accompanying the new paper. “Always speak to your medical professional before changing or initiating a treatment.”

But researchers Sarris are gradually disentangling potential fact from fiction. A number of vitamins and supplements are coming under scientific scrutiny. Vitamin D in particular has been the focus of a host of recent studies and may be beneficial in treating a variety of conditions, from multiple sclerosis to schizophrenia.  

For brain health, all—or at least most—roads lead to the sea.  Many small trials have reported associations between omega-3 fatty acids—obtained either through diet or supplements—and improved depression symptoms.

In practice, omega-3s derived from fish appear to reach significantly higher blood levels than those sourced from plants.

And there is a fast accumulating body of data linking a reduced risk for depression to traditional diets—including the Mediterranean, Scandinavian and Japanese diets—that are high in vegetables, whole grains and fish.

How does the evidence sit in light of the new study’s findings? “It is important to advise that a balanced whole-food diet is important for physical as well as mental health, and that supplements should not replace this,” Sarris notes. “However, I believe a good diet in addition to select nutraceutical prescriptions can still be recommended in some cases, such as when people have inadequate responses to antidepressant medication.”

As a next step, Sarris believes researchers should move beyond specific supplements and study augmenting antidepressant treatment with, say, the Mediterranean diet. Both he and Jacka also feel that more work needs to be done to determine which supplements may benefit patients as individuals, their specific nutrient deficiencies, brain conditions and genetic profiles.

“A key imperative for nutritional psychiatry is to develop a clear understanding of what supplements are useful for whom, and under what conditions, and also to understand the baseline factors that might influence nutrient metabolism, such as gut health,” Jacka says. “This sort of knowledge should help us to begin to design targeted and personalized nutritional interventions for psychiatric illnesses.”

Source: https://www.scientificamerican.com/article/do-vitamins-and-supplements-make-antidepressants-more-effective/

Supplements including fish oil and vitamin D can boost effects of antidepressant medications

Taking fish oil boosts the effect of antidepressant medicines

Taking some nutrient supplements together with antidepressants can enhance the medication’s effects, our research has found.

Published this week in the American Journal of Psychiatry, our review of the evidence found that omega-3 fish oil, methylfolate, vitamin D and amino acid compound S-adenosine methionine (known as SAMe) supplements increased the effects of antidepressant medication for those with clinical depression.

We reviewed 40 clinical trials that explored the effects of using nutrient supplements together with antidepressants as therapy for clinical depression.

The strongest finding in our meta-analysis – a combination of outcome data from several studies into one analysis – was that taking omega 3 fish oil supplements high in the fatty acid EPA, in combination with antidepressants, was significantly more effective than a dummy pill.

Many studies have shown omega-3 supplements are good for general brain health and improving mood. But this is the first analysis of studies that looks at using the supplements in combination with antidepressant medication for clinical depression.

Our findings mean we have an evidence-based, safe approach that could be considered a mainstream treatment for depression. But we advise anyone considering changing or initiating treatment to consult their doctor.

Nutrients and mental health

Dietary nutrients, such as vitamins B, C and D, omega-3 fatty acids and minerals such as zinc and magnesium, are critical for brain health. We also know that when given as supplements, they may be beneficial to mental health.

Doctors recommend some of these supplements in cases where a blood test has confirmed nutrient deficiencies. But doctors are often hesitant to advise using supplements as part of mental health therapy. This is partly because it’s unknown whether prescribing nutrients with antidepressants is more effective for depression, and whether there are safety concerns about this approach.

To answer these questions, our research team from the University of Melbourne and Harvard Medical School examined worldwide trials from the 1960s to today. The studies had aimed to see if certain nutrients were effective in improving a person’s depression when taken together with different types of antidepressants, such as the popular selective serotonin re-uptake inhibitors (SSRIs).

Overall, we found more patients in the studies showed an improvement in mood when prescribed omega-3 fish oil, methylfolate, vitamin D and SAMe supplements in combination with antidepressant medication, compared to those who took medication only.

Research shows many with depression still experience some symptoms after months of treatment with antidepressant medications. from shutterstock.com

The evidence revealed mixed results for zinc, vitamin C and tryptophan (an amino acid molecule that is a precursor to some neurotransmitters such as serotonin). Folic acid didn’t work particularly well, nor did the compound inositol (a small molecule structurally similar to glucose).

How nutrients could complement medications

We are increasingly understanding how some nutrients may improve depression.

Omega-3 and SAMe, for instance, can alter mood-regulating neurotransmitter levels in the brain in a similar way to certain antidepressant medications.

Other nutrients, when taken together with antidepressants, could potentially give depression sufferers the extra boost they need as they may work on an additional range of brain chemical pathways. Omega-3 and zinc, for instance, may act by reducing inflammation, which has been implicated in depression.

Nearly 2 million Australians take antidepressants. But research shows many with depression still experience some symptoms despite several months of treatment with antidepressant medication.

The mental health of people who have an inadequate response to antidepressants can potentially be improved by supplementing their use with nutrients. Clinicians and the public can consider therapeutic doses of particular nutrients as a potential low-cost approach to reducing depression in these instances.

Our evidence review found no major safety concerns in combining many of the nutrient supplements studied with medications, but it is important to stress that supplements can differ in quality. We advise people to always speak with their medical professional before changing or initiating any treatment.

It is also important for those suffering from depression to see medications and supplements as one potentially important element in an integrative approach. This should include psychological care and consideration of lifestyle factors, such as a good wholefood diet, exercise and sufficient sleep.

We are recruiting for an NHMRC-funded clinical trial in Melbourne and Brisbane to see if using these nutrients in combination will enhance the effects of antidepressant medication even more.

Source: http://theconversation.com/supplements-including-fish-oil-and-vitamin-d-can-boost-effects-of-antidepressant-medications-58484

Fish oils for depression?

Taking fish oil boosts the effect of antidepressant medicines

A 58-year-old man's condition was stable on a selective serotonin reuptake inhibitor (SSRI) after 3 major depressive episodes in the previous 10 years. He disd the idea of taking a drug for a long time and at one point took himself off the SSRI and started taking St. John's wort.

However, the reappearance of symptoms of depression soon persuaded him to resume the SSRI. As discussed in a previous column (J Psychiatry Neurosci 2003;28:471), he decided, on the advice of his physician, not to try over-the-counter preparations of S-adenosylmethionine or 5-hydroxytryptophan.

However, he continued to look for a more “natural” treatment to prevent the recurrence of depression. Research on the Web convinced him that eating more fish or taking fish oils might be the answer, but he had several questions.

Is there good evidence for the effectiveness of fish oils? Should he eat more fish or take fish oil supplements? If he took supplements should he take one with higher levels of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA)? Is there a concern about mercury or polychlorinated biphenyls in fish and fish oils?

Recent meta-analyses have looked at the effect of fish oils (omega-3 fatty acids) on depression. Most studies, all of which are relatively small, looked at the effect in patients with unipolar or bipolar depression who were already taking antidepressants or mood stabilizers.

Different studies looked at the effect of EPA, DHA or their combination, and the dosages varied from 1 to 9.6 g daily. Although the meta-analyses indicated a significant antidepressant effect, different studies gave markedly discrepant results.

No factors, such as dosage or the use of EPA or DHA, could be identified to account for the discrepancies. There is also the possibility of a publication bias.

Given that no studies have looked at the ability of fish oils to prevent the recurrence of depression and that the evidence for the treatment of depression remains preliminary, it would be inappropriate to advise the patient to substitute fish oils for the SSRI. However, adding fish oil supplements to the SSRI could be beneficial.

The American Heart Association recommends that healthy adults eat at least 2 servings of fish a week, particularly fish with higher levels of DHA and EPA, such as mackerel, lake trout, herring, sardines, albacore tuna and salmon (www.americanheart.org/presenter.jhtml?identifier=3006624).

There is evidence that increased intake of fish oils is beneficial for the heart, and the possibility that fish oils may also help prevent depression, while not supported by evidence, remains plausible.

Given that no dose-response relation was seen in the meta-analyses of depression treatment, a daily intake of 1 g (DHA plus EPA), the lowest dose used in the clinical trials, is reasonable. Fish oil supplements may have some advantages over fish consumption.

Epidemiologic evidence relates increased fish consumption to a decreased incidence of depression, but no clinical trials have been done with fish consumption. Further, tests of a limited number of over-the-counter fish oil supplements have revealed negligible contents of mercury and organochlorines, including polychlorinated biphenyls, whereas these compounds are a concern with fish intake.

In summary there is not sufficient evidence to suggest the use of fish oils for the treatment of depression and no evidence for the prevention of depression. Nonetheless, fish oils are good for the heart, have no demonstrated adverse effects when taken in reasonable dosages, and could potentially be beneficial for mood.

Although patients should be discouraged from taking fish oils as a substitute for antidepressants or mood stabilizers, if they wish to take fish oils as an adjunct to those treatments, they should be aware of the tentative nature of the evidence for a beneficial effect on mood and inform themselves about possible contaminants.

Simon N. Young, PhD Department of Psychiatry McGill University Montréal, Que.

The information in this column is not intended as a definitive treatment strategy but as a suggested approach for clinicians treating patients with similar histories. Individual cases may vary and should be evaluated carefully before treatment is provided.

Psychopharmacology for the Clinician columns are usually a case report that illustrates a point of interest in clinical psychopharmacology.

They are about 500–650 words long and do not include references. Columns can include a bibliography that will be available only with the online version accessible at www.cma.ca/jpn.

Competing interests: None declared.

1. Foran SE, Flood JG, Lewandrowski KB. Measurement of mercury levels in concentrated over-the-counter fish oil preparations: is fish oil healthier than fish? Arch Pathol Lab Med 2003;127:1603-5. [PubMed]

2. Freeman MP, Hibbeln JR, Wisner KL, et al. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry 2006;67:1954-67. [PubMed]

3. Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry 2007;68:1056-61. [PubMed]

4. Melanson SF, Lewandrowski EL, Flood JG, et al. Measurement of organochlorines in commercial over-the-counter fish oil preparations: implications for dietary and therapeutic recommendations for omega-3 fatty acids and a review of the literature. Arch Pathol Lab Med 2005;129:74-7. [PubMed]

Articles from Journal of Psychiatry & Neuroscience : JPN are provided here courtesy of Canadian Medical Association

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2186366/

Antidepressant– effects of fish, krill oils and Vit B12 against exposure to stress environment in mice models: current status and pilot study

Taking fish oil boosts the effect of antidepressant medicines

Oxidative stress has significant role in pathophysiology of any kind of depression through actions of free radicals, non-radical molecules, and unbalancing antioxidant systems in body.

In the current study, antidepressant responses of fish oil (FO), Neptune krill oil (NKO), vitamin B12 (Vit B12), and also imipramine (IMP) as the reference were studied. Natural light was employed to induce stress in the animals followed by oral administration of the drugs for 14 days.

The antidepressant effect was assessed by tail suspension test (TST) and forced swimming test (FST), antioxidant enzymes and oxidative stress markers were then measured in the brain tissue of the animals.

The administration of FO and NKO could significantly reduce the immobility of the animals; while, increasing climbing and swimming time compared to the normal saline in CUS-control group in TST and FST, similarly to IMP but not with Vit B12.

Vit B12 could not effect on SOD activity and H2O2 level, but, cause decrease of the malondialdihydric (MDA) level and CAT activity, as well as increased the GPx and GSH activities. The rest treatments led to decrease of MDA, H2O2 levels and CAT activity and increase of GPx, SOD, GSH activities.

Depression is a chronic and devastating psychological complaint that millions of people suffer. Since 1950s up to the present time, antidepressants only have treated this disorder serendipitous alteration through the monoamine neurotransmitters, such as serotonin or noradrenaline.

However, fundamental patho-physiological mechanisms of such illness are not fully understood1,2, but different pharmacologic therapeutics have been recently developed for managing depression3. It is demonstrated that administration of natural antidepressants in induced stress rodents are able to alleviate related symptoms4,5.

Physicians are encouraged to search for natural compounds as effective drugs due to their lower side effects compared to the chemical drugs. For instance, recent findings show that omega-3 fatty acids are able to improve depression and anxiety, effectively without having serious adverse effects6.

In addition, it is well understood that n-3 polyunsaturated fatty acids (n-3 PUFAs) which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), possess some bioactivity effects, such as, anti-inflammatory, anti-nociceptive, antioxidant, anti-depressant, anti-anxiety, anti-cardiovascular, etc.7,8.

For instance, brain is made up to 60% of different lipids which are mostly made of PUFAs, particularly, DHA9 which contribute to healthy brain and improve variety of brain functions, such as memory and learning10,11. Bloch and Hannestad12 demonstrated that EPA and DHA contain only a little or even no-significant antidepressant effects, without having any noticeable differences.

However, Sublette et al.13 suggested that only those supplements which consist of EPA ≥ 60% of the total EPA and DHA possess an effective anti-mild-depressant activity. It is reported that either fish oil or krill oil which is extracted from small shrimp planktonic crustacean of open seas, possess high level of essential polyunsaturated lipids, EPA and DHA14.

In addition of fatty acids, some vitamins have shown to possess mild antidepressant effect and are prescribed by physicians to improve patient’s depression and anxiety. As an example, administration of Vit B12 as an exogenous antioxidant at dose of 1 mg/daily to those patients suffering from depression [20] can improve variety of symptoms of mental and depression disorders15.

To study effectiveness of drugs as antidepressant in rodents, some distinctive and clear depressive behaviours before and after treatments have been suggested to be assessed with some reliable tests, such as tails suspension (TST) and forced swimming tests (FST). In FST, novel antidepressant drugs in comparison with the control group could reduce immobility in animals.

Also, some other behaviours, such as swimming and climbing are strongly suggested to be scored separately16. Swimming time is increased by selective serotonin reuptake inhibitors, on the contrary, climbing is motivated by selective norepinephrine reuptake inhibitors.

In both tests, the immobility time of animals is related to the state of depression which is expected to decrease by using effective antidepressants17.

The role of ROS, such as H2O2 or MDA which are formed from lipid peroxidation of polyunsaturated fatty acids in depression is strongly highlighted18,19,20 and show to associate with lowering antioxidant defence or failure to repair oxidative damage.

In order to eliminate the harmful effects of oxidative stress, body can get benefit from both endogenous and exogenous antioxidant systems21,22.

Studies show that antidepressants affect antioxidant systems in brain to subside of free radicals to alleviate the symptoms of such disorders23,24.

In the present novel work, antidepressive–effects are evaluated in four different groups of animals which are treated by IMP, FO, NKO, Vit B12 to find their different actions against depression.

Also, SOD, CAT, GPX, and GSH activity (major endogenous antioxidant enzymes) and also MDA and H2O2 level (oxidative stress markers) of the hippocampal of the experimental animals are assessed. Also the effect of the compounds on the enzymatic systems is evaluated to find out their connection to antidepressant- effect.

Furthermore, the aforementioned activities of FO and NKO are compared together and to a moderate natural antidepressant (Vit B12) and also to imipramine as a strong chemical antidepressant.

Effect on the immobility time by the oral daily treatments is exhibited in Fig. 1.

Analysis showed that FO, NKO, Vit B12 and IMP could significantly decrease the time of immobility compared to the CUS group with no significant difference with control group.

There was no noticeable difference between NKO, FO, and Vit B12 and also noticed that IMP was more effective to increase the immobility time than the other three supplements.

Figure 1

Effects of drugs on immobility time in TST. All animals (n = 90), except the control groups (n = 18) receive CUS. CUS (n = 9) and control (n = 9) animals do not receive any drugs or vehicle and the rests are orally administered with vehicle and the treatments.

The treated groups (n = 72) are treated with FO (0.32 g/kg/day, n = 18), NKO (0.5 g/kg/day, n = 18), Vit B12 (1 mg/kg/day, n = 18) and IMP (5 mg/kg/day, n = 18). Results are expressed as mean ± SEM of immobility time (in seconds).

Differences are analysed using two-way ANOVA followed by post hoc Dunnett’s test. For statistical significance, *p 

Source: https://www.nature.com/articles/s41598-019-56360-8