Arthritis Drug Effective for Depression in Psoriasis Sufferers

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Depression Treatment Drug

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 blood."

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 it.

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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.

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