Prophylactic antidepressant treatment in patients with hepatitis C on antiviral therapy: a double-blind, placebo-controlled trial.

BACKGROUND: Approximately one-third of patients undergoing interferon-α (IFN-α) therapy for treatment of the hepatitis C virus (HCV) develop major depression, which decreases functioning and may lead to the reduction or discontinuation of treatment. OBJECTIVE: The authors examined the efficacy of citalopram in preventing IFN-α-induced depression in HCV patients. METHOD: This was a randomized, controlled trial comparing citalopram with placebo in 39 HCV patients. RESULTS: The rate of IFN-α-induced depression in the sample was 15.4% (6/39). Randomization to citalopram did not decrease the statistical likelihood of developing IFN-α-induced depression (10.5% for citalopram vs. 20.0% for placebo). CONCLUSION: Citalopram does not prevent depression onset; however, an empirically-supported treatment recommendation for IFN-α-induced depression includes monitoring depressive symptoms throughout antiviral therapy and initiating psychiatric treatment at the initial signs of depression.

The influence of antiviral therapy on psychiatric symptoms among patients with hepatitis C and schizophrenia.

BACKGROUND: Antiviral therapy for chronic infection with HCV is associated with significant neuropsychiatric side effects. Research indicates that patients with mental illness are less likely to receive antiviral therapy, despite limited data regarding the influence of antiviral therapy on psychiatric symptoms in patients with specific psychiatric disorders. The aim of this study was to determine whether antiviral therapy is associated with higher rates of psychiatric symptoms in patients with schizophrenia (SCHZ). METHODS: A regional Veterans Healthcare Administration database was used to identify veterans meeting criteria for this retrospective chart review. Patients confirmed to have SCHZ and to have received antiviral therapy for HCV between 1998 and 2006 (n=30) were compared with a control group of demographically matched (age, race and gender) patients with SCHZ who did not receive antiviral therapy (n=30). Clinicians blinded to antiviral therapy status used chart notes to evaluate whether patients exhibited prominent symptoms of SCHZ, depression or mania during a 6 month pre-treatment period, the treatment period and a 6 month post-treatment period (or during equivalent periods for the control group). RESULTS: Groups did not significantly differ in rates of symptoms of SCHZ, depression or mania during any study period. During the treatment period, groups did not significantly differ in rates of emergency room visits or inpatient hospitalizations. CONCLUSIONS: Our retrospective chart review suggests that patients with SCHZ experience similar rates of psychiatric symptoms on and off antiviral therapy. Despite limitations and constraints of the methods, our data suggest that SCHZ is not a contraindication to antiviral therapy for HCV.

Antiviral therapy completion and response rates among hepatitis C patients with and without schizophrenia.

BACKGROUND: Despite disproportionately high rates of hepatitis C (HCV) among patients with severe mental illness, to date, there is scant empirical data available regarding antiviral therapy outcomes within this population. OBJECTIVE: To compare antiviral therapy completion and response rates between HCV patients with vs those without schizophrenia (SCHZ). METHODS: A regional Veterans Healthcare Administration database was used to identify veterans meeting criteria for this retrospective chart review. All patients confirmed to have SCHZ and to have received antiviral therapy between 1998 and 2006 (n = 30) were compared with a control group of demographically matched (HCV genotype, age, race, gender) patients with no history of SCHZ (n = 30). RESULTS: For HCV patients with genotype 1, antiviral completion, end of treatment response (ETR), and sustained viral response (SVR) rates did not significantly differ between groups. For those with genotypes 2 and 3 combined, antiviral therapy completion rates did not significantly differ between groups; however, the SCHZ group was significantly (P < 0.050) more likely to achieve an ETR and an SVR. For all genotypes combined, the SCHZ patients were no more likely than controls to discontinue therapy early for psychiatric symptoms, medical complications, or other adverse events, and groups did not significantly differ in terms of hospitalization rates during antiviral therapy. CONCLUSION: Our retrospective chart review suggests that patients with SCHZ complete and respond to antiviral therapy for HCV at rates comparable with those without SCHZ. Based on these data, SCHZ should not be considered a contraindication to antiviral therapy for HCV.

Antiviral completion rates and sustained viral response in hepatitis C patients with and without preexisting major depressive disorder.

BACKGROUND: Despite evidence suggesting that the majority of patients with hepatitis C virus (HCV) have psychiatric and substance use disorders, patients with these comorbidities have historically been excluded from antiviral therapy for HCV. OBJECTIVE: The authors compared antiviral completion and sustained virologic response (SVR) rates between hepatitis C (HCV) patients with versus those without preexisting major depressive disorder (MDD). METHOD: The authors performed a chart review of HCV patients (30 with MDD and 25 control subjects) who attended an optional HCV education class and signed informed consent allowing collection of clinical data. RESULTS: The MDD group had completion and SVR rates similar to those of control subjects. Neuropsychiatric side effects and reasons for discontinuation of treatment were not different between groups. CONCLUSION: Patients with MDD can be safely and effectively treated with antiviral therapy.

Pain, substance use disorders and opioid analgesic prescription patterns in veterans with hepatitis C.

To examine the prevalence of pain, substance use disorder (SUD) diagnoses, and opioid analgesic prescription patterns among veterans infected with the hepatitis C virus (HCV), a retrospective review of the medical records of 8,224 HCV-positive (HCV+) veterans was performed. Twenty-nine percent and 46% of HCV+ patients were prescribed opioids in the prior one and three years, respectively. Sixty-seven percent of HCV+ patients had documented pain diagnoses and 56% had SUD diagnoses. Patients with co-occurring pain and SUD were less likely to be prescribed opioids than patients with pain only (prior year: 36% vs. 43%, P<0.001; three years: 56% vs. 60%, P<0.01). There were no differences in numbers of early opioid prescription fills or numbers of opioid prescribers when comparing patients with co-occurring pain and SUD to patients with pain only. Veterans with co-occurring pain and opioid use disorder had fewer early opioid fills than veterans with pain only (prior year: 2.6 vs. 5.3 days, P<0.01; three years: 6.1 vs. 13.4 days, P<0.001). These data demonstrate that pain and SUD diagnoses were common among HCV+ patients, and that opioids were frequently prescribed. Co-occurring SUD was not associated with indicators of prescription opioid misuse.

Depressive symptoms in patients with chronic hepatitis C are correlated with elevated plasma levels of interleukin-1beta and tumor necrosis factor-alpha.

Studies suggest that cytokines have a role in the biology of depression. In this study, we evaluated depression and cytokine levels in patients with and without chronic hepatitis C (HCV) to better assess how chronic infection alters cytokines levels and may contribute to depressive symptomotology. Twenty-three adults with (n=16) and without (n=7) HCV were recruited through the Portland VA Medical Center. Research participants were excluded for current substance abuse, psychotic disorder, liver cirrhosis, or interferon (IFN) therapy. Participants completed the Beck Depression Inventory-II (BDI-II) and a blood draw to evaluate plasma cytokine levels [i.e., interleukin (IL)-1beta, IL-10 and tumor necrosis factor (TNF)-alpha]. t-Tests were performed to compare cytokine levels in patients with or without HCV. HCV patients showed higher TNF-alpha values compared to patients without HCV (group means=7.94 vs. 3.41pg/mL, respectively, p=0.047). There were no significant differences between the groups for the other cytokines assessed. In patients with HCV, TNF-alpha and IL-1beta levels (but not IL-10) were correlated with BDI-II scores [r=0.594, p=0.020 and r=0.489, p=0.055 (trend), respectively]. Taken together, these results show an association between severity of depressive symptoms and expression of pro-inflammatory cytokines in patients with HCV. Future studies should investigate how inflammatory mediators play a role in the expression of specific depressive symptoms in patients with chronic infection. Patients with HCV represent an interesting model to examine this relationship.