Antidepressants: Best for Severe Depression?

Some antidepressants may work best for people with very
severe depression , according to a new analysis, but may provide little or no
benefit over placebo for those with mild, moderate, or severe depression.

''For patients with very severe depression, the medication did have a potent
effect compared to placebo," says Jay C. Fournier, a psychology graduate
student at the University of Pennsylvania, Philadelphia, and  lead author
of the analysis, published in the Journal of the American Medical

But, he says, ''the effects of the active ingredients of the medication were
pretty small or nonexistent for patients with mild or moderate depression or
even into the severe range."

However, the analysis only looked at two antidepressants.

Effects of Antidepressants: Study Details

Fournier and his colleagues pooled the results of six previously published
studies that compared the effects of antidepressants to placebo for 718 adults
with varying levels of depression.

Three of the studies looked at paroxetine (Paxil) and the others looked at
imipramine (Tofranil).

Paxil is a type of antidepressant known as an SSRI (selective serotonin
reuptake inhibitor), which is thought to boost mood by making more of the
neurotransmitter serotonin available in the brain. Other popular SSRIS include
citalopram (Celexa), fluoxetine (Prozac), and sertraline (Zoloft).

Tofranil is an older medication, known as a tricyclic antidepressant, which
works by making more of the neurotransmitters serotonin and norepinephrine

In the new analysis, Fournier's team only included studies that met their
criteria. Studies, for instance, had to have individual patient data, not just
overall results.

And the patients evaluated had a broader range of depression severity than
those in most studies. Although many other studies only look at severely
depressed patients (with a score of 23 or above on a commonly used scale known
as the Hamilton Depression Rating Scale), Fournier's team evaluated studies
that included patients with scores in the low teens, considered mild or
moderate depression, through the 30s, or very severe.

Effects of Antidepressants: Study Results

''We were looking for differences between placebo and medications," Fournier
tells WebMD. "We were interested in whether there was a clinically meaningful
difference." One way the researchers defined ''clinically meaningful" was to
have an improvement of three or more points on the Hamilton scale between
placebo takers and medicine users.

''The main finding is that the benefit of medication, over and above the
placebo, varied as a function of the severity of the depression," he says. "The
effect of the medication for the mild, moderate, and even severe fell below
this three-point difference that would be clinically significant."

The analysis suggests that some depressed people do respond to placebo, he
says, and that severely depressed people are most likely to benefit from

Even so, he tells WebMD, individual treatment decisions should be made in
consultation with a physician.

Other Opinions

The study results are no surprise to Peter Galier, MD, an internal medicine
specialist and former chief of staff at Santa Monica--UCLA Medical Center &
Orthopaedic Hospital, Santa Monica, Calif.

''Much like any other disease process, the more severe the disease or
symptoms, the more improvement with treatment," he says.

But the analysis doesn't give a complete picture of the effects of
antidepressants, says Gregory Asnis, MD, a professor of psychiatry at Albert
Einstein College of Medicine and director of the anxiety and depression clinic
at Montefiore Medical Center in New York, who reviewed the analysis for

"The data is unfortunately skewed to two medications, only one of wich
[Paxil] is still commonly used," Asnis says.

And Paxil, he finds, can have more side effects, such as sedation and sexual
problems, than some of the other SSRI drugs.

The finding of greater differences between placebo and medication in only
the severely depressed was not a surprise to him, either, he says. However, he
says, the studies were short-term (6 to 11 weeks) and the benefit of the
medication could have kicked in later.

Industry Comments

''The study contributes to the extensive research that has helped to
characterize the role of antidepressants over the years," says Sarah Alspach, a
spokeswoman for GlaxoSmithKline, which makes Paxil. "Since its approval by the
FDA in 1992, Paxil has helped millions of people battling mental illness lead
more productive, happier lives. Antidepressants are an important option, in
addition to counseling and lifestyle changes, for treatment of depression."

A spokesperson for Eli Lilly, which makes the antidepressant Prozac,
declined comment on the new analysis.

In an email, Alan Goldhammer, vice president of scientific and regulatory
affairs for the Pharmaceutical Research and Manufacturers of America (PhRMA),
says, "This is a matter best addressed by companies whose drugs were studied
and the individual physicians who are tasked with making treatment decisions
based on which therapies are best suited for treating their patients."

By Kathleen Doheny
Reviewed by Louise Chang
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