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Neuropsychiatric side effects associated with interferon plus ribavirin for treatment of hepatitis C: Recognition and risk factors

Charles L Raison, MD
Nezam H Afdhal, MD, FRCPI
Section Editor
Jonathan M Silver, MD
Deputy Editor
David Solomon, MD


Neuropsychiatric side effects are common in patients who receive interferon plus ribavirin, and these adverse effects can cause treatment failure and clinical decisions to not start treatment in the first place [1]. The regimen of interferon plus ribavirin is rarely used in the United States.

This topic reviews recognition and risk factors for neuropsychiatric side effects in patients receiving interferon plus ribavirin for hepatitis C virus infection. Treatment and prevention of these side effects are discussed separately. (See "Neuropsychiatric side effects associated with interferon-alfa plus ribavirin therapy: Treatment and prevention".)


The neuropsychiatric side effect most often associated with interferon plus ribavirin for hepatitis C virus is depression. Depression occurs on a continuum ranging from subsyndromal symptoms to minor depression and major depression. The clinical manifestations and diagnosis of the different types of depression are discussed separately. (See "Unipolar depression in adults: Assessment and diagnosis".)

Studies of depression associated with interferon plus ribavirin vary in the type of depression that was assessed. Some studies have characterized depression as a single symptom (feeling down or sad) [2,3], while other studies have defined depression as a syndrome characterized by a defined set of emotional and physical symptoms [4-8]. In still other studies [1,9-11], depression was assessed as a severity score on questionnaires that asked about symptoms not necessarily recognized as part of major depression in the American Psychiatric Association's Diagnostic and Statistical Manual, Fifth Edition (DSM-5) [12]. Generally, depression is more common when viewed as a single symptom or as a score on a rating scale than when it is defined as the syndrome of major depression (table 1) [13].

The incidence of unipolar major depression in patients with hepatitis C who are treated with interferon plus ribavirin is high. A meta-analysis of 22 prospective observational studies examined the incidence of major depression in 1391 euthymic patients with chronic hepatitis C who started interferon plus ribavirin [14]. Following onset of treatment, the cumulative incidence of major depression was as follows at:

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Literature review current through: Nov 2017. | This topic last updated: Nov 21, 2016.
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