Only patients with severe depression consistently receive substantial relief; omega-3s yield positive brain effects and show increasing clinical promise
by Craig Weatherby

Back in 2008, we reported what happened when British researchers used Freedom of Information requests to obtain unpublished studies funded by drug firms.

The results showed that pharmaceutical corporations may have been misleading doctors and patients for decades.

After analyzing all of the published and unpublished data, scientists at Britain's University of Hull found that for most depression patients, Prozac-type anti-depressants produce no significant benefits compared with placebo pills.

The only exception to this rule was that minor benefits were detected among a small group of the most severely depressed patients.

And their analysis indicated that the benefits seen in some severely depressed patients stem from their relatively weak responses to the placebo effect, rather than any greater efficacy of SSRIs among this group.

For that story, see “Prozac-Type Drugs Proven No Better than Placebo.

Now, the American authors of a new evidence review have also concluded that on average, anti-depressants only benefit severely depressed patients.

New analysis echoes earlier, negative findings on antidepressants
This week, researchers at the University of Pennsylvania reported what happened when they scrutinized data from previous clinical trials (Fournier JC et al 2010).

The trials they examined tested members of the two major two classes of antidepressants: newer Prozac-type drugs called selective serotonin re-uptake inhibitors (SSRIs) and older ones called tricyclics.

The several large trials they reviewed had tested the effects of Paxil (an SSRI) and the tricyclic-type antidepressant drug called imipramine.

Like the two-year-old British review, the new analysis done by researchers at the University of Pennsylvania found that the effectiveness of both drugs varied according to the severity of a participating patient's depression.

On average, only people with severe depression showed substantial improvements.

As the Pennsylvania team wrote, “The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms.”

Antidepressants remain useful for some
It's also important to note what the Pennsylvania group went on to say: “For patients with very severe depression, the benefit of medications over placebo is substantial” (Fournier JC et al 2010).

But as co-author Robert J. DeRubeis told The New York Times, “The message for patients with mild to moderate depression is, ‘Look, medications are always an option, but there's little evidence that they add to other efforts to shake the depression—whether it's exercise, seeing the doctor, reading about the disorder or going for psychotherapy.'”

And Oregon Health and Science University psychiatrist Erick H. Turner, M.D., told the Times, “I think the study could dampen enthusiasm for antidepressant medications a bit, and that may be a good thing. People's expectations for the drugs won't be so high” (Carey B 2010).

However, we also agree with Dr. Turner's cautionary caveat: “The findings shouldn't dampen expectations so much that people refuse to even try medication” (Carey B 2010).

The British and American findings are startling, but do not mean that people with mild or moderate symptoms shouldn't even try an antidepressant... if all else has failed.

Although on average they got little benefit, a minority of mildly or moderately depressed patients received more substantial relief than the majority of their peers did.

In addition, brain imaging studies show that antidepressant drugs stimulate growth of new brain cells in the hippocampus region—shrinkage of which correlates closely with the depth and length of a patient's depression—so they may therefore at least prevent further progression of the disease.

But similar brain-cell growth in the hippocampus is also a benefit of omega-3s from fish oil.

Omega-3s show promise
Omega-3s and SSRI drugs alike foster growth of cells in the brain's hippocampus region, and connections between hippocampus brain cells… an effect associated with reduced depression risk and symptom severity.

And in mouse studies, omega-3s and Prozac both restore brain cells' ability to take on new roles and form new connections, which eases the symptoms of depression (Sahay A, Hen R 2008; Venna VR et al. 2009).

For more on this, see “Bogus Headlines Distort Omega-3 Depression Study.

Omega-3s are also essential to the proper function of brain-cell membranes, and studies led by NIH clinical researcher Joseph Hibbeln, M.D., suggest that dietary omega-3s raise brain levels of the mood-elevating neurotransmitter called serotonin (Hibbeln JR et al. 1998).

This is the very same effect, by different means, through which SSRI drugs like Prozac are thought (but not proven) to bring some of their benefits

Three years ago, the Committee on Research on Psychiatric Treatments of the American Psychiatric Association (APA) reviewed the evidence then available, and concluded that people who consume higher amounts of omega-3s from fish enjoy reduced risks of mood disorders (See “Top Psych Panel Says Omega-3s Deter Depression, Bipolar Disorder”).

And as we reported last August, the results of the largest-ever clinical trial comparing omega-3s to antidepressants bolstered that conclusion, finding that omega-3 fish oil may significantly benefit half of all people diagnosed with depression.

Specifically, omega-3 fish oil seemed to help the 50 percent of depression patients who are free from diagnosed anxiety disorders… about as much as the leading class of antidepressant drugs: selective serotonin re-uptake inhibitors (SSRIs) such as Prozac and Paxil.

See “Fish Oil Rivals Antidepressants in Clinical Trial” and search our newsletter archive for “depression.”

  • Fournier JC et al. Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-analysis. JAMA. 2010;303(1):47-53.
  • Carey B. Popular Drugs May Help Only Severe Depression. The New York Times, January 6, 2010. Accessed at