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Arthritis Drug Effective for Depression in Psoriasis Sufferers

Arthritis Drug Effective for Depression in Psoriasis  Sufferers
Arthritis Drug Effective for Depression in Psoriasis  Sufferers


Duke Health News Duke Health News

Durham, N.C.— Etanercept (trade name Enbrel), approved for
treating rheumatoid arthritis, effectively reduces not only the
symptoms of the disease, but also depression and fatigue in
psoriasis sufferers, according to a multi-university research
team that includes a scientist at Duke University Medical
Center. Etanercept, an antibody that blocks tumor necrosis
factor-alpha, significantly improved the symptoms and
depression associated with the disorder, the researchers
reported in an article published online Dec. 14, 2005 by
The Lancet.

High concentrations of pro-inflammatory substances called
cytokines, such as tumor necrosis factor-alpha (TNF-alpha),
have been associated with major depression. According to Ranga
Krishnan, M.D., the study author based at Duke, researchers
have long hypothesized that reducing the effects of the
cytokines may reverse depressive symptoms. Until now, no
research team has examined the effects of a tumor necrosis
factor receptor on depression in humans.

The phase III clinical trial was primarily designed to test
the effectiveness of etanercept in improving the clinical
symptoms of psoriasis, a chronic skin disease characterized by
silvery, scaling bumps and raised patches of very dry skin. In
severe cases, people can experience joint pain similar to that
of rheumatoid arthritis. Psoriasis sufferers frequently
experience problems with both depression and fatigue as a
result of their disease.

"It has been shown that when you are sick or depressed,
tumor necrosis factor concentration increases," said Krishnan,
chief of psychiatry and behavioral sciences at Duke. "When
TNF-alpha goes up, the symptoms are very similar to what is
termed 'sickness behavior' and previous studies have shown that
when a person is depressed, TNF-alpha levels are increased in

The team wanted to determine whether etanercept would have
any effect on the symptoms of depression that are so common
among people with psoriasis.

The research team followed 618 study participants at 39
study sites in the randomized, double-blinded study.
Participants received either 50 milligram twice-weekly
subcutaneous injections of etanercept or matching placebo for a
period of 12 weeks (placebo =307; etanercept =311), which
constituted the placebo-controlled portion of the study.
Subsequently, the participants were followed for 84 weeks
during which all the participants received etanercept and knew

The researchers measured responses using the psoriasis area
and severity index score (PASI), the dermatology life quality
index, the functional assessment of chronic illness therapy
fatigue scale, the Hamilton rating scale for depression (Ham-D)
and the Beck depression inventory (BDI).

The researchers found that nearly half (47 percent) of
participants achieved 75 percent or greater improvement in
their clinical symptoms of psoriasis at week 12 while taking
etanercept, compared to five percent of those on placebo having
the same effect.

Notably, researchers found significant improvements on the
BDI in the etanercept group in feelings of guilt, irritability,
interest, appearance, work, sleep and sexual symptoms, compared
with those receiving placebo. Ham-D scores for those receiving
the etanercept showed improvements to insomnia, work,
hypochondriasis and sexual problems when compared to the
placebo group.

The etanercept group also showed lower levels of fatigue,
with the improvement strongly correlated to improvements in
joint and skin pain due to psoriasis, according to the
researchers. Improvement in depression levels could not be
correlated to improvement in those symptoms. However, the
researchers point out that the study was not designed to detect
the effect of etanercept on primary depression.

"While depression scores improved, we cannot be sure why,"
Krishnan said. "Our next step is to run this type of trial in
people who have depression but not psoriasis. At this point, no
one should run to their doctor and ask for this drug for
depression. However, the science is very exciting to us."

The team's work is an important first look in humans at how
a TNF antibody could improve secondary symptoms of depression,
said Krishnan. Further research will unveil more clues to how
TNF receptors work in the brain and may eventually lead to
improved treatments for depression.

Krishan's work on this trial was supported by Amgen, but he
holds no financial interest in the company or etanercept.
Funding for the study was provided by Amgen. The primary study
was designed by Immunex, the company responsible for developing
etanercept. Amgen acquired Immunex in 2002.

Other authors on the study include Stephen Tyring, MD,
University of Texas Health Science Center at Houston; Alice
Gottlieb, MD, UMDNJ-Robert Wood Johnson Medical School; Kim
Papp, MD, University of Western Ontario, London, Ontario and
Probity Medical Research, Waterloo, Canada; Ken Gordon, MD,
Evanston Northwestern Healthcare – Skokie, Ill.; David Cella,
Ph.D., Evanston Northwestern Healthcare – Evanston, Ill.; Craig
Leonardi, MD, St. Louis University School of Medicine; Andrea
Wang, Deepa Lalla, Ph.D., Michael Woolley, Ph.D., Angelika
Jahreis, MD, and Ralph Zitnik, MD, of Amgen.

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