The standard treatment for hepatitis C today is a combination of pegylated interferon (PEG-Intron/Schering-Plough or Pegasys/Hoffman LaRoche) and the antiviral medication, ribavirin.1 But one potential side effect of interferon therapy is depression.2
Approximately 20-50 percent of patients taking interferon alfa therapy can experience depression depending on the dose and duration of the therapy.
Mood and Treatment Response
Now, doctors contend that depression during such treatment may be an indicator of subsequent poor response.3 Researchers at Emory and Cornell Universities evaluated 102 patients with chronic hepatitis C taking part in an unrelated study to determine whether symptoms of depression can be a predictor of poor treatment outcome.
"Depression has been linked to a worse outcome in multiple medical disorders, including viral illnesses," wrote Charles Raison, MD, an assistant professor in the department of Psychiatry and Behavioral Sciences at Emory, and his colleagues in explaining the reason for their research.
Raison explained that over the past decade, there has been a large amount of research suggesting that depression is a mortality risk factor. As well, the risk of developing illnesses like heart disease, cerebral vascular disease, and possibly diabetes and metabolic syndrome, might be tied to depression, he said. That was the basis for this study.
Since depression is a potential side effect of interferon treatment, Raison's group wanted to determine if it affected treatment response or not. "We got interested in the question of whether or not people who develop those symptoms [of depression] are less likely to have the medicine work," said Raison, who is also director of the Behavioral Immunology Clinic at Emory.
Looking for a Connection
Each patient was examined by a psychiatrist at the beginning of the study, and again at 4, 8, 12 and 24 weeks after treatment began. Each patient was taking pegylated interferon alfa-2b (PEG-Intron/Schering-Plough Pharmaceuticals) plus ribavirin.
At the end of the research, Raison's team learned that while 34 percent of the patients who had faced significant increases in depression cleared the hepatitis virus from their bloodstream after 24 weeks of therapy, up to 69 percent of patients with milder increases in depression did so. The effect of depression on viral clearance continued even after taking into account whether medication doses had to be reduced or not, as well as viral genotype. It's well known that people with genotype 1 HCV have more difficult treatment outcomes than those with other genotypes.4
The study ended at 24 weeks of treatment, and even though this is not considered a sustained response, the researchers point to other studies that have suggested that early virologic response (EVR) to treatment is a significant predictor of a sustained virologic response (SVR).5 SVR is defined as no evidence of the hepatitis C virus in a person's bloodstream 6 months beyond the end of 24 or 48 weeks of treatment, depending on genotype.6
"Indeed, EVR is now routinely used to make treatment decisions in patients receiving pegylated interferon/ribavirin," they wrote.
Reasons for this Possible Link
At this point, it's unclear why treatment-related depression is associated with responses to therapy, the scientists wrote, but add that it may have something to do with the effect of depression on treatment adherence. Some patients may prematurely drop therapy due to the side effects. Further, physicians will often reduce the dose with the aim of easing side effects. But neither of this occurred in this study, Raison explained.
Thus, another possibility is that the relationship between pegylated interferon and depression may, somehow, be intertwined in immune and nervous system regulation, Raison's group wrote. In other words, "there's a connection between the physiology of depression and the physiology of viral clearance," Raison told Priority Healthcare.
Previous studies have suggested that depression may be associated with increases in inflammation in the body, he said. And its known that interferon triggers the production of pro-inflammatory cytokines, proteins secreted by the immune system during its attack against a disease-causing organism like the hepatitis virus, explained Raison. "Many of us are beginning to believe that psychological stress is not so different than, say, catching a bacterium," he said.
Inflammation be the Answer
A handful of previous research has also suggested that people who respond to interferon with increased production of pro-inflammatory cytokines may be less likely to clear the hepatitis virus, Raison said, but why isn't known. That may be the link between depression and viral clearance, he added, but that is only speculation.
In treatment-related depression, medical experts have focused primarily on a patient's quality of life or whether the condition would convince a patient to stop taking medication. Now, this study suggests that depression might even predict poor response to treatment, Raison said.
"The findings of this study provide preliminary evidence that baseline mood state should be assessed in patients prior to commencing treatment," Raison said.
Depression May Boost Treatment Outcome
At least one other study has contradicted these findings.7 In research involving 39 people infected with chronic hepatitis C given interferon alfa, about one-third became depressed. The researchers at Portland VA Medical Center in Oregon found that those who showed depressive symptoms had significantly better treatment outcomes than those who weren't depressed. Specifically, 61 percent of those with depression responded to interferon treatment compared to about 27 percent of those with out depression. "In conclusion, our findings suggest that interferon-alfa-induced major depressive disorder may be a predictor of a positive response to interferon-alfa therapy, or an indication of optimal dosing," the study authors wrote.
But Raison has reservations. "It's very unusual for depression to be good for people's health, which is something about that study that would make one a little cautious," he said.
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3. Raison CL, Broadwell SD, Borisov AS et al. Depressive symptoms and viral clearance in patients receiving interferon-alfa and ribavirin for hepatitis C. Brain Behav Immun 2005 Jan;19(1):23-7.
4. Trepo C. Genotype and viral load as prognostic indicators in the treatment of hepatitis C. J Viral Hepat 2000 Jul;7(4):250-7.
5. Davis GL, Wong JB, McHutchinson JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 2003 Sep;38(3):645-52.
6. Fried MW, Shiffman ML, Reddy KR et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C infection. N Engl J Med 2002 Sep 26;347(13):975-82.
7. Loftis JM, Socherman RE, Howell CD et al. Association of interferon-alfa-induced depression and improved treatment response in patients with hepatitis C. Neurosci Lett 2004 Jul 22;365(2):87-91.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
