Abstract
In patients at high risk for recurrence of malignant melanoma, interferon-α (IFN-α), a stimulator of innate immunity, appears to induce distinct neurobehavioral symptom dimensions: a mood and anxiety syndrome, and a neurovegetative syndrome, of which the former is responsive to prophylactic administration of paroxetine. We sought to determine whether symptom dimensions (and treatment responsiveness) arise in patients with hepatitis C administered IFN-α and ribavirin. In a randomized, double-blind, 6-month study, 61 patients with hepatitis C eligible for therapy with IFN-α and ribavirin received the antidepressant paroxetine (n=28) or a placebo (n=33). Study medication began 2 weeks before IFN-α/ribavirin therapy. Neuropsychiatric assessments included the 10-item Montgomery–Asberg Depression Rating Scale (MADRS). The items of the MADRS were grouped into depression, anxiety, cognitive dysfunction, and neurovegetative symptom dimensions, and analyzed using a mixed model. By 2 weeks of IFN-α/ribavirin therapy, all four dimensions increased, with the symptom dimensions of anxiety and cognitive dysfunction fluctuating and worsening, respectively, in both groups over time. The depression symptom dimension was significantly lower in the paroxetine treatment group (p=0.04); severity of the neurovegetative symptom dimension was similar in both groups. Similar to patients with malignant melanoma receiving high-dose IFN-α, the depression symptom dimension is more responsive to paroxetine treatment in individuals undergoing concomitant IFN-α/ribavirin therapy. However, the anxiety, cognitive dysfunction, and neurovegetative symptom dimensions appear less responsive to prophylactic paroxetine administration. Different neurobiologic pathways may contribute to the responsiveness of IFN-α-induced symptom dimensions to antidepressant treatment, requiring relevant psychopharmacologic strategies.
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Acknowledgements
We thank the many patients who gave their time and effort to help complete this study. The trial is registered with ClinicalTrials.gov under identifier NCT00352885. This work was supported by Schering-Plough and GlaxoSmithKline, and by grants from the National Institute of Mental Health (MH060723, MH64619, MH00680, MH071580, and MH60723) and an NIH/NCRR General Clinical Research Center grant (M01 RR00039).
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Charles L Raison serves as a consultant for Biolex Therapeutics and Pamlab. Andrew H Miller has served as consultant for Abbott Laboratories, AstraZeneca, GlaxoSmithKline, Lundbeck Research USA, F Hoffmann-La Roche, Schering-Plough Research Institute, and Wyeth/Pfizer, and has received research support from Centocor, GlaxoSmithKline, and Schering-Plough Research Institute. The remaining authors declare no conflict of interest.
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McNutt, M., Liu, S., Manatunga, A. et al. Neurobehavioral Effects of Interferon-α in Patients with Hepatitis-C: Symptom Dimensions and Responsiveness to Paroxetine. Neuropsychopharmacol 37, 1444–1454 (2012). https://doi.org/10.1038/npp.2011.330
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