Hepatitis C Treatments: Their Link to Depression and Implications for the Social Worker The most commonly used treatment for patients suffering from Hepatitis C, a deadly liver disease, is the drug interferon combined with ribavirin. This treatment offers the most promise for a long-term positive prognosis. However, it has a known high rate for negative psychological side effects such as depression and other anxiety disorders. Clinical psychology can offer some solutions to this problem, both in assessing those patients who have increased risk factors for depression such as substance abuse or a history of depression, and in offering treatments to help ease the occurrence and severity of depression. This study will assess the risk for depression among the general population of Hepatitis C patients on interferon therapy.

Introduction

Hepatitis C virus is the most common liver disease in the United States. Approximately 1.8% of the U.S. population are infected, with approximately 74% of those persons chronically infected. Approximately 8-10 thousand people die each year from this disease (Darko, et. al., 2000). Although clinical trials indicate that Interferon/Ribavirin treatments produce significantly better clinical results in the long-term for hepatitis C patients, it is not recommended for those who have a history of depression. Many studies indicate that for people prone to depression ribavirin/interferon therapy can make their condition significantly worse (Mitchell, 2001). This treatment can cause depression in as many as 25% of all people who use it (Boutiler and Hosein, 2000). Fortunately, it was found that this depression does respond to standard treatments for depression such as Prozac and other antidepressants (Boutiler and Hosein, 2000).

Depression is a well-documented side effect of Interferon/Ribavirin treatment. Depression from Hepatitis C treatments can range from mild to severe. In some cases, the symptoms may be so severe that the person must decide between severe side effects and the continuance of a life-saving treatment. Some severe cases have even been known to lead to suicide. The following research will assess past studies concerning the risk of depression for persons who have Hepatitis C and who are taking Interferon/Ribavirin treatments.

Literature Review

The most widely accepted treatment for Hepatitis C involves varying doses of the drug interferon or long acting Pegylated interferon combined with the drug ribavirin. This standard therapy is sold under the brand name Rebetron (Boutiler and Hosein, 2000). It offers many possibilities for patients both newly diagnosed and for those who have had a relapse after interferon therapy (Mitchell, 2001).

The exact mechanisms of how these drugs work against Hepatits C. are not known. However, this group of drugs is the most widely tested in clinical trials against the disease and are now considered standard therapy. Ribavirin has an action against some viruses. It is a synthetic drug and the mechanisms of how it works against Hepatitis C are not fully understood. Ribavirin alone has not been found to be effective for the long-term. For this reason that it is used in combination with interferon or pegylated interferon.

Interferon is found naturally in the body as a defense against viral infections. The interferon used to treat hepatitis C is a synthetic copy of the interferon found naturally in the body. It is thought that interferon works by stimulating the processes in cells that slow down the growth and reproduction of the virus.

Pegylated interferon is produced by attaching polyethylene glycol (PEG) molecules to interferon. This aids the interferon in several ways. It acts as a shield to the interferon so that the body cannot attack it and break it down as rapidly. PEG also makes the interferon molecule larger so that it remains in the blood longer and does not escape through the blood vessel walls as quickly into other parts of the body. Pegylated interferon only needs to be injected once a week as opposed to three times a week for regular interferon (Mitchell, 2001). Ribavirin/interferon therapy shows positive results in the long-term from 31-49% above people using interferon alone (Mitchell, 2001). This therapy is the most effective treatment for Hepatitis C available today.

There are two positions concerning Hepatitis C and depression. The first is that patients with psychiatric disorders have a higher prevalence of Hepatitis C it is estimated that 74-100% of all intravenous drug users are infected with Hepatitis C (Fisher and others, 1997). The second is that patients with chronic Hepatitis C may have a higher incidence of depression (Yates and others, 1998). It is clear that high rate of depression occurs in Hepatitis C patients, however, the reasons for this depression are unclear.

Two things stand out in the population of persons with Hepatitis...

First, they are young and may have concerns over their long-term outcome. Many are between 30-40 years old (Alter and others, 1999). In addition, they tend to come from populations such as substance abusers, who tend to have a higher incidence of depression as compared to the normal population (Johnson and others, 1998). Depression can be a significant factor in the treatment of Hepatitis C (Dusheiko, 1997).
As Rebetron therapy is known to increase the symptoms of depression in persons taking this treatment (Capuron and Ravaud, 1999), it should be a consideration in the overall treatment plan for the patient. It may sometimes be difficult to distinguish pre-existing depression from that induced by the Rebetron (Johnson and others, 1998). Most studies conducted on the Hepatitis C patients have been conducted in tertiary care studies and may not reflect the result that would be obtained in the general population with the disease (Darko and others, 2000). These results may contain a significant amount of sample bias due to the population chosen.

Studies reproducing significantly high numbers of patients on Rebetron with depression are numerous and concurrent. Renault and others (1987) reports that psychiatric effects occur in 17% of all patients treated for Hepatitis C the severity of the depression changed across different studies and it is not known if the results obtained were from patients on similar dosages of interferon (Renault and others, (1987), Miyaika and others, (1998) and McHutchinson and others, (1998)). It is not known if variations occurred as a result of higher and lower doses of interferon or if the duration of therapy had an effect (Renault et al., (1987), Miyaika et al., (1998) and McHutchinson et al., (1998)). The consistent factor across the studies examined is that patients with a history of depression are significantly more susceptible to interferon-induced depression than those without a psychiatric history (Dusheiko, 1997). Several studies confirm that interferon may worsen alcohol and substance abuse (Dusheiko, 1997). Due to this factor, it is not known if interferon-induced depression in these patients is actually a relapse of alcohol or substance abuse (Darko et al., 2000).

It would at first seem from the studies presented, that the connection between depression and interferon use is clear, however, several things must be considered when examining the studies presented. First, all of the studies used different exclusion criteria. Secondly, all of the studies used different scales and variables to assess depression. It should be noted that depression induced by interferon is not unique to patients suffering from hepatitis C Depression is also seen in patients suffering from Hepatitis B, hairy cell leukemia, AIDS, melanoma and other similar diseases. Rates of depression ranges from 0-50% (Adams and others, (1994) and Misiani and others, (1994)).

The exact physiology of Interferon Induced depression is not completely understood. It is believed from the pattern of personality changes that it may be a frontal-subcortical brain dysfunctional (Pavil and others, 1995). Brown and others (1991) suggests that serotonin depletion might be responsible for the reported interferon-induced depression syndrome. Although the mechanism is unclear, it would seem as if altered seratonin levels are responsible for interferon induced depression. This would be consistent with the physiology associates with other forms of depression.

Interferon-induced depression can be severe in some cases and can linger for some time after treatment has been discontinued. Interferon-induced depression can lead to suicidal thoughts (Younossi, (1997) and Funikashi and others, (1998)) with the act being carried out in many cases (Janssen and others, (1994) and Rifflet and others (1998)). Depression does not always go away after Rebetron is discontinued and the patient must continue to undergo psychiatric monitoring and treatment. There is also a risk of switching patients from depression to mania with antidepressant therapy, which can also continue after the treatment is discontinued (Carpiniello and others, 1998). Patients suffering from Interferon-induced depression may need psychological services long after Hepatitis C treatments have stopped.

Despite a lack of published literature, there is a growing opinion that SSRIs may be the preferred agents for treating all types of depression, including interferon-induced depression. These agents appear to be safe and well tolerated in the patients with liver disease (Franco-Bronson, 1996). In McKeown (2001), persons with malignant skin cancer were given the antidepressant Paxil for two weeks before they started chemotherapy with high-dose interferon. Only 11% developed depression compared with 45% of those who did not receive Paxil before interferon therapy (Mckeown, 2001). In Fried and others (2001), patients…