It is estimated that 130 to 150 million people currently suffer from chronic hepatitis C virus (HCV) infection.1 The prevalence of chronic HCV infection is among the highest in patients with severe underlying mental illness. The treatment of hepatitis C has evolved over the past 2 decades and transitioned from interferon-α (IFN-α) monotherapy to pegylated IFN-α in combination with ribavirin therapy; both are nonspecific immunotherapies.
There has recently been a shift in hepatitis C treatment guidelines with the emergence of a new class of agents: direct-acting antivirals (DAAs) that have revolutionized treatment of the infection. DAAs offer improved rates of HCV infection “cure,” defined as sustained virological response (negative HCV RNA, 24 weeks post treatment). They also require a shorter duration of treatment and have a more favorable adverse-effect profile than previous hepatitis C medication regimens (Table 1). The most common adverse effects associated with DAAs are fatigue and insomnia (Table 2). The reduced psychiatric risks with DAAs are salient developments to hepatitis C therapy, given that up to 50% of patients with untreated chronic HCV infection suffer from psychiatric illness when substance abuse and dependence are excluded.2
In the past, patients with severe comorbid psychiatric illnesses had been considered “high risk” for HCV infection treatment primarily because of the neuropsychiatric adverse-effect profile associated with IFN-α. Although HCV-infected patients with psychiatric comorbidity can be effectively treated in integrated care models with psychiatric support, the introduction of newer DAAs may further increase access to hepatitis C treatment for these patients.3-5
The focus on hepatitis C treatment adherence with DAAs has redefined psychiatrists’ role in collaborative or integrated care models for HCV infection. This article explores several implications pertaining to the psychiatric care of patients undergoing hepatitis C treatment and sheds some light on the changing role of psychiatrists amid evolving hepatitis C therapies and care models.
A limitation of IFN-α therapy has been its adverse neuropsychiatric effects, specifically depression, which can compromise the management of HCV-infected patients who have a preexisting history of psychiatric illness. It is estimated that the rates of IFN-α–induced depression range from 25% to 30%; this can result in severe complications, such as patient suicide, if the depression is poorly controlled.6
Several proposed mechanisms for IFN-α–induced depression have been cited in the literature; however, much of the evidence suggests associated changes in the serotonergic system.7,8 Reductions in both tryptophan and plasma serotonin concentrations following the administration of IFN-α have been reported. It is believed that IFN-α transcriptionally activates indoleamine 2,3-dioxygenase, the rate-limiting enzyme of tryptophan conversion into kynurenine, the major (90%) nonprotein pathway of tryptophan metabolism.9,10 Other studies have identified a deficiency of serotonin production from tryptophan as a risk factor for developing IFN-α–induced depression (Figure).11,12 These abnormalities appear to resolve in most cases approximately 6 months after completion of IFN-α therapy.
The management of IFN-α–induced depression consists of an initial assessment for baseline depressive symptoms before the start of immunotherapy. Standardized depression scales can be used to evaluate the baseline psychopathology and the presence of an MDD before starting hepatitis C treatment. After initiating IFN-α therapy, clinicians should monitor patients for potential IFN-α–related adverse effects, such as anemia and hypothyroidism, that may cause or contribute to depressive symptoms.
A recent meta-analysis and systematic review found that prophylactic administration of an SSRI, such as paroxetine or escitalopram, before starting antiviral treatment for chronic HCV infection reduces the incidence of a major IFN-α–induced depressive episode by 43%.13
Antidepressants, such as SSRIs, mirtazapine, and bupropion, have been efficacious in treating IFN-α–induced depression when it emerges during hepatitis C treatment.14-16 Regardless of the approach to antidepressant therapy, monitoring and routine follow-up every 2 weeks for at least the first 3 months after initiation of IFN-α therapy is required for all high-risk patients and continuous monitoring thereafter for stable high-risk patients.
Dr Thiara is Research Assistant in the department of psychiatry at the University Health Network, Toronto; Dr Sackalingam is Deputy Psychiatrist-in-Chief at the University Health Network and Associate Professor in the department of psychiatry at the University of Toronto. The authors report no conflicts of interest concerning the subject matter of this article.
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