SSRI Therapy to Manage Depression in Patients With Hepatitis C Virus: A 72 Week Retrospective Study

Background and Purpose: Pegylated interferon used to treat and cure hepatitis C virus (HCV) is known to induce neuropsychiatric adverse effects, specifically cytokine-induced depression. Treatment guidelines for HCV require a mental health evaluation prior to the start of treatment.  Mental health professionals are tasked with management of cytokine-induced depression and indications for antidepressant therapy. Prior studies indicate viral cure of HCV may be associated with cytokine-induced depression. Though antidepressants are often used to treat cytokine-induced depression, it is uncertain whether anti-inflammatory properties of SSRIs used to treat cytokine-induced depression inadvertently contravene pro-inflammatory properties of pegylated interferon (Peg-IFN) in effect reducing therapeutic efficacy.  The purpose of this study was to determine whether SSRI therapy interferes with viral cure of HCV.

Methods:  This was a retrospective cohort study that recruited patients from baseline (week 0) to follow up (week 72) who previously underwent and completed pegylated interferon treatment for HCV at a gastroenterology clinic in northeast Georgia. The sampling frame comprised a list of 456 patients with a HCV diagnosis attending this clinic. Patients meeting the following criteria were included in the study: HCV positive, received treatment, completed treatment, and returned for follow up. Patients were excluded from the study if they did not complete the prescribed treatment or completed treatment but failed to return for follow up. Approximately 240 (43%) patients received combination therapy for HCV but after applying inclusion and exclusion criteria only 46 (19%) were included in the study sample. The primary outcome was sustained virological response (SVR) and was measured by a laboratory test known as HCV by polymerase chain reaction. The exposure of interest in this study was treatment with SSRI therapy. Cytokine-induced depression was determined using self-reported neuropsychiatric symptoms recorded in the medical record. A bivariate analysis was performed to determine the relation between the primary outcome and SSRI use. A bivariate analysis stratified by cytokine-induced depression was performed to assess the effect of cytokine-induced depression on the outcome. Generalized estimating equations were used in a multivariate analysis to estimate change in HCV viral logs over time and to control for potential confounding variables. An autoregressive correlation matrix was used to account for the correlations of measurements over time.

Results: SSRI therapy did not adversely impact the proportion of patients achieving SVR (P=0.50), and neither did cytokine-induced depression (P=0.62). In a multivariate longitudinal analysis, the mean slope of HCV RNA levels declined faster over time in patients without cytokine-induced depression in comparison to patients with cytokine-induced depression (P=0.05), and the mean slope of HCV RNA levels declined similarly over time in patients with and without SSRI therapy.

Conclusions and Implications: In this retrospective cohort study, SSRI therapy did not interfere with immune activation dynamics of pegylated interferon, and patients without cytokine-induced depression developed quicker responses and suppressed HCV replication more favorably over time. This suggests mental health professionals may safely adopt a practice of recommending SSRI therapy to manage cytokine-induced depression with limited concerns of it adversely impacting likelihood of a viral cure of HCV.