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Bad News on Prozac & Co.; Good Mood News on Fish

New dangers seen in depression drugs; fish offer a double dose of mood-lifting nutrition

by Craig Weatherby

You may recall an article in our last newsletter about the promise of omega-3 fatty acids in helping prevent or alleviate seasonal affective disorder (SAD): a mild-to-moderate form of depression brought on by short, dark winter days.

And, the majority of population studies indicate that people who consume lower amounts of omega-3s suffer higher rates of depression.  Sadly, Americans are among the populations who don't get enough omega-3s, and whose rates of depression—including childhood depression—are high and increasing.

Alarming new concerns over antidepressant drugs

Today's headlines brought more disturbing news about popular antidepressants such as Prozac, Paxil, and Zoloft, which belong to the widely prescribed class of drugs called selective serotonin reuptake inhibitors (SSRIs).

A study in the current issue of the British Medical Journal, whose results were released today, provides powerful reasons for people and their physicians to seek alternative preventive and therapeutic approaches to depression.

An analysis of 702 controlled clinical trials involving 87,650 patients found that adults taking SSRI-type antidepressants are more than twice as likely to attempt suicide as patients given a placebo.  (The increased risk of suicide was also found in people taking an older class of antidepressants called tricyclics.)

This new finding about adults on antidepressants follows close on the heels of the FDA's conclusion last year that SSRI-type antidepressants increase the rate of suicidal thoughts and behavior among children: a determination that led the agency to require rare “black box” warnings on SSRI drug labels.

Over-prescription of “happy pills”?

David Healy, M.D., one of the authors of the paper, decried what he calls the overuse of SSRIs.  While antidepressants help some seriously depressed people, many expert medical critics believe that too many people who don't really need them are prescribed what the BMJ article called "happy pills."

In December of 2004, Britain's equivalent of the FDA determined that general practitioners prescribe SSRIs for far too many people who do not suffer from serious depression: a conclusion that probably applies to this country.  Anecdotal reports in the media suggest that increasing numbers of younger, non-depressed white collar workers use SSRIs in a misguided attempt to enhance their professional performance and interactions.

Nutrition versus depression

This disturbing news about the suicide-impulse dangers of anti-depressant drugs serves to highlight the problem of treating depression safely, and underscore the important of reducing the risk or severity depression through any means possible, including diet.

As we've reported, most studies indicate that populations that consume high amounts of omega-3 fatty acids—mostly from fish—enjoy lower rates of depression.

To date, there have been only two clinical studies of the therapeutic value of omega-3s for depression.  Unfortunately, they involved very different doses, and reached opposite conclusions.

One study showed that omega-3s alleviate major depression to a significant degree, while the other study found no benefit.  However, the positive study employed much higher daily doses—6.6 grams of omega-3s, versus 2 grams in the negative study—and lasted two weeks longer (eight weeks versus six weeks).

While we await the results of planned clinical research designed to clarify the therapeutic value of omega-3s in depression, the intriguing results of a new animal study suggest that fish may offer a synergistic anti-depressant effect beyond the benefits offered by their omega-3s.

Fish offers two mood boosting factors

Researchers at Harvard-affiliated McLean Hospital report that omega-3 fatty acids and uridine—two naturally occurring substances in fish—prevented the development of signs of depression in rats just as effectively as antidepressant drugs. In the study, researchers examined how omega-3 fatty acids and uridine affected the behavior of rats exposed to depression-inducing stress.

As the Mclean team concluded, “Uridine and OMG [omega-3 fatty acids] each have antidepressant-like effects in rats. Less of each agent is required for effectiveness when the treatments are administered together.”

And, as lead author William Carlezon, PhD explained, "Giving rats a combination of uridine and omega-3 fatty acids produced immediate effects that were indistinguishable from those caused by giving the rats standard antidepressant medications.”

Of course, we can't be sure that these results would be the same in humans, but rats are considered reasonably reliable models for testing the efficacy of anti-depressant drugs.

The Perricone connection

And there's an apparent connection between these findings and the anti-aging hypotheses proposed by, among other researchers, Nicholas Perricone, M.D.  (He's the subject of an article in this issue: see “Dr. Perricone's NYT Profile.”)  Dr. Perricone believes that the preponderance of research indicates that aging is driven largely by a decline in the energy-producing capacity of mitochondria, which are the vital microscopic “furnaces” found in every cell in the body.

Study co-author Perry Renshaw, MD, PhD explained the connection between these nutrients and mitchondrial function: "Omega-3 fatty acids may make the mitochondrial membranes more flexible and uridine may provide raw material to make chemical reactions occur more readily. These conditions would be more conducive to the production of energy, and boost communication among neurons in key areas of the brain."

In fact, there's growing evidence that the brain's mitochondria may be involved in mood regulation. For example, researchers recently found dramatic alterations in mitochondrial genes within the brains of people with bipolar disorder, which is characterized by alternating cycles of elation and depression.

We should note that in addition to occurring in fish, both of these substances—omega-3 fatty acids and uridine—are also found in walnuts, molasses and sugar beets.  But of the four food sources cited by the Mclean researchers, only fish offers substantial quantities of long-chain omega-3s (e.g., EPA and DHA): the type that possesses proven anti-depressive properties.

These findings provide a possible explanation for reputation of fish as anti-depressive “good mood food.”


  • Fergusson D et al. Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ  2005 Feb 19;330:396.
  • Gunnel D et al. Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review. BMJ  2005 Feb 19;330:385.
  • Carlezon WA Jr, Mague SD, Parow AM, Stoll AL, Cohen BM, Renshaw PF. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry. 2005 Feb 15;57(4):343-50.
  • Freeman MP. Omega-3 fatty acids in psychiatry: a review. Ann Clin Psychiatry. 2000 Sep;12(3):159-65. Review.
  • 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):267-71. Erratum in: Eur Neuropsychopharmacol. 2004 Mar;14(2):173.
  • Haag M. Essential fatty acids and the brain. Can J Psychiatry. 2003 Apr;48(3):195-203. Review.
  • 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):996-8.
  • Mischoulon D, Fava M. Docosahexanoic acid and omega-3 fatty acids in depression. Psychiatr Clin North Am. 2000 Dec;23(4):785-94. Review.


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