Abstract and Introduction
Objective: Evaluate the incidence of mental disorders using pegylated interferon plus ribavirin retreatment in nonresponder hepatitis C virus-infected patients.
Method: The Mini-International Neuropsychiatric Interview (MINI) was used to evaluate 30 hepatitis C virus-infected interferon-nonresponder patients at baseline and following 4, 12 and 24 weeks of pegylated interferon retreatment.
Results: During the pegylated interferon/ribavirin retreatment, 5(16.6%) patients developed psychiatric side effects: 3(10%) were diagnosed with major depressive disorder, 1(3.3%) had a brief psychotic disorder and 1(3.3%) presented with panic attacks.
Conclusion: This is the first prospective study evaluating the incidence of neuropsychiatric side effects during interferon retreatment of hepatitis C virus-infected patients, suggesting that the risk of acquiring serious psychiatric symptoms during retreatment with interferon-α (IFN-α) may not be higher than during the first antiviral therapy. This finding challenges the hypothesis that during a second treatment with IFN-α, patients with hepatitis C may be at greater risk for neuropsychiatric side effects than naïve patients.
Interferon-α (IFN-α) has been used in combination with ribavirin (RBV) in the treatment of patients with hepatitis C virus (HCV), resulting in sustained virological response (SVR), in about 50% of patients. However, among patients with HCV genotype 1 infection treated for 48 weeks, the rate of SVR is lower than 30%. A new preparation of pegylated IFN-α (PEG IFN), both α-2a and α-2b have an extended half-life and appear to increase rates of sustained viral response, while offering the convenience of once-a-week dosing. The adverse events reported with the use of the two drugs were similar, because these are structurally similar products.
Retreatment with IFN-α is often necessary to obtain the necessary viral eradication. Despite its therapeutic benefit, many studies report that repeated administration of IFN-α in patients with chronic active hepatitis may induce neuropsychiatric side effects, especially symptoms of major depression. In selected cases, treatment might be reduced or interrupted, directly affecting the outcome, because adherence to IFN-α therapy is essential to achieving a SVR. Thus, a decrease in side effects during therapy with IFN-α should lead to a higher compliance rate among patients and have the best antiviral efficacy.
Several risk factors are thought to increase the probability of emergent psychiatric comorbidity during IFN-α treatment, such as previous history of psychiatric illness, history of substance abuse, family history of psychiatric illness and history of suicidal ideation. Although these factors are not well validated, they have been used as exclusion criteria in several large HCV clinical trials. Several studies demonstrated that gender is not a risk factor for developing depressive symptoms during IFN therapy; however, not all studies corroborate this finding. Only one study indicated advanced age as a risk factor for major depression. RBV has also been reported to be associated with increased depression. Therefore, RBV and IFN might be independently associated with the occurrence of depressive symptoms in the treatment of HCV-infected patients.
There is reason to believe that IFN-α retreatment represents an additional risk factor to the occurrence of depression. There is evidence that administration of this cytokine activates corticotrophin-releasing factor (CRF) production and increases the cerebrospinal fluid concentration of CRF, which are common findings among depressive patients. In addition, there is experimental evidence suggesting that a second exposure to a stressful stimulus can sensitize the hypothalamic-pituitary-adrenal (HPA) axis and produce an exacerbated glucocorticoid response. Therefore, it is reasonable to hypothesize that a second IFN-α exposure could increase the rate of depression among HCV-infected patients. IFN-α antiviral retreatment has already been suggested as a potential risk factor to depression in this population. However, we could not find in any study the literature evaluating psychiatric side effects during IFN retreatment in HCV-infected individuals.
Therefore, we have designed the first study to prospectively evaluate the incidence of mental disorders during PEG IFN/RBV retreatment in HCV-infected patients nonresponders to the first antiviral treatment.