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| Subscribe to Clinical Compass™ | VOLUME 3, ISSUE 12 - JUNE 3, 2008 | ||||||||||||||||||||||||
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Hepatitis C and Depression by Eleanor Roberts, PhD In the United States there are an estimated 4.1 million people infected with hepatitis C virus (HCV). While 15% to 25% of people newly infected will clear the virus spontaneously, the majority will need pharmacologic intervention. Currently the FDA-approved forms of treatment are interferons alfa-2a or -2b (IFN alfa-2a or -2b), which may be covalently bound to polyethylene glycol (peg-IFN alfa), and are typically combined with ribavirin (RBV). Approximately one-third of people receiving therapy will experience treatment-induced depression, which can lead to the need for dose decreases or medication discontinuation. Iatrogenic depression is related to type of treatment, dose, duration, and route of administration.(1) For instance, the addition of RBV may increase/induce depression, with one investigation finding that depression ratings followed a dose-response relationship.(2) In general, antidepressants are useful in the alleviation of treatment-induced depression. In one study, patients administered pegIFN alfa-2b + RBV who subsequently developed depression (n = 28 of 100 participants) were given citalopram 20 mg/day or placebo. Scores on the Hospital Anxiety and Depression Scale were significantly decreased in the citalopram group (p < .001), and were significantly lower than placebo patients (p = .032).(2) Some suggest that all patients with HCV be administered an antidepressant with IFN treatment, however, as antidepressants themselves have iatrogenic effects this practice is not universally advocated. This is supported by two double-blind, placebo-controlled studies that investigated the use of prophylactic paroxetine. One study, which utilized the major depression module of the Structured Clinical Interview for DSM-IV, showed that rates of depression were not different in the paroxetine (up to 40 mg/day) and placebo groups during therapy. They concluded “a prophylactic approach to IFN alfa-induced depression may not be indicated in patients with HCV infection”.(3) Similarly, when Raison et al 2007(4) administered either paroxetine (10-20 mg/day, n = 28) or placebo (n = 33) from 2 weeks prior to IFN alfa + RBV therapy, and for 24 weeks after treatment initiation, rates of depression did not differ between the groups. It is of note, however, that those in the Raison et al study(4) whose baseline scores on the Montgomery Asberg Depression Rating Scale (MADRS) were above the median (> 3), the severity of depression was significantly lower at all points between weeks 12 to 24 (around an 8 point difference) for the paroxetine group compared to the placebo group. This suggests that prophylactic antidepressants may be useful for those who are showing signs of depression before treatment. Thus it may be of use clinically to try to determine which patients are more likely to develop depression; indeed one group showed that although depression does not usually develop for at least 8 weeks after treatment, at 4 weeks, high vegetative-depressive scores on the Zung Depression Rating Scale (which includes lack of sleep, loss of appetite, loss of sex drive, weight loss, and fatigue) were 95% predictive of those who later developed depression.(5) This rating scale, along with the MADRS, could be used to administer prophylactic treatment only to those whose ratings are high either before treatment or, if signs of depression develops due to treatment, as soon as 4 weeks after initiation. In conclusion, depression in patients with HCV infection is a common comorbidity of which clinicians need to be aware. It is of utmost importance that all patients are screened for depression before starting HCV therapy and that patients are monitored for symptoms of depression throughout treatment. This may present the need for the setting up and education of multidisciplinary teams involved in separate aspects of HCV and depression treatment. For further education related to management of HCV infection please visit www.cmeoutfitters.com/CC310. For further education and resources regarding major depression, please visit www.neurosciencecme.com/resources_knowledge_depression.asp. Another useful website containing a number of depression rating scales is www.neurotransmitter.net/depressionscales.html. Do you have feedback for the author? Click here to send us an email. References
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