Psychiatric clearance for patients started on interferon-alpha-based therapies.

Abstract

Increasingly, psychiatrists are asked to provide “psychiatric clearance” for patients who are to be treated with a regimen that includes recombinant preparations of interferon-alpha (IFN-a), often in combination with other antiviral medications. The most common use for IFN-a is in the treatment of chronic hepatitis C, which affects about 2% of the general U.S. population and about 20% of people with severe mental illness (1). Each year, more people in the United States die from hepatitis C complications, such as severe cirrhosis and hepatocellular cancer, than from HIV. IFN-a is also used, in combination with other medications, to treat some cancers, such as metastatic melanoma. This recombinant inflammatory cytokine has been associated with adverse effects on mental health, worse quality of life, increased risk for suicide, and treatment discontinuation. Most patients develop some fatigue and loss of appetite during treatment, which can be severe but is usually tolerable. However, 10%–40% additionally develop a full depressive disorder syndrome that can include suicidal ideation, amotivation, social withdrawal, guilt, anhedonia, irritability, anxiety, and crying (2–8). Untreated depression is a major contributor to dosage reductions or treatment discontinuations and consequent risk for viral relapse (9–11). Additionally, many patients with hepatitis C already have preexisting mental health disorders (12) that often go unrecognized (13). Such disorders can adversely affect a person’s ability to tolerate a 24to 48-week course of antiviral IFN-a therapy. In addition to depression during IFN-a treatment, many patients (up to 25%) may develop anger and irritability (14–17), which can be independent of depression. These symptoms can occasionally be serious enough to result in road rage, spousal discord, and problems at work. Another common side effect of IFN-a is severe fatigue. Less commonly, mania, delirium, and psychosis can occur. Monitoring for these various psychiatric side effects, as well as distinguishing among these distinct conditions, is one role for the psychiatrist. Also, coadministered medications such as telaprevir and boceprevir (antiviral protease inhibitors) can inhibit cytochrome P450 (CYP) 3A4, resulting in increased blood levels of many psychiatric medications. A knowledge of psychopharmacology and potential medication interactions is thus also important. Finally, IFN-a treatment commonly has mild side effects such as nausea and malaise and occasionally is complicated by severe hematologic abnormalities. Both sustained adherence and psychosocial stability are necessary, even in patients who do not develop frank neuropsychiatric syndromes.