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Borrego-Ruiz A, Borrego JJ. Involvement of virus infections and antiviral agents in schizophrenia. Psychol Med 2025; 55:e73. [PMID: 40059820 PMCID: PMC12055031 DOI: 10.1017/s0033291725000467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 02/06/2025] [Accepted: 02/12/2025] [Indexed: 05/08/2025]
Abstract
BACKGROUND Schizophrenia is a chronic and complex mental disorder resulting from interactions between cumulative and synergistic genetic and environmental factors. Viral infection during the prenatal stage constitutes one of the most relevant risk factors for the development of schizophrenia later in adulthood. METHODS A narrative review was conducted to explore the link between viral infections and schizophrenia, as well as the neuropsychiatric effects of antiviral drugs, particularly in the context of this specific mental condition. Literature searches were performed using the PubMed, Scopus, and Web of Science databases. RESULTS Several viral infections, such as herpesviruses, influenza virus, Borna disease virus, and coronaviruses, can directly or indirectly disrupt normal fetal brain development by modifying gene expression in the maternal immune system, thereby contributing to the pathophysiological symptoms of schizophrenia. In addition, neuropsychiatric effects caused by antiviral drugs are frequent and represent significant adverse outcomes for viral treatment. CONCLUSIONS Epidemiological evidence suggests a potential relationship between viruses and schizophrenia. Increases in inflammatory cytokine levels and changes in the expression of key genes observed in several viral infections may constitute potential links between these viral infections and schizophrenia. Furthermore, antivirals may affect the central nervous system, although for most drugs, their mechanisms of action are still unclear, and a strong relationship between antivirals and schizophrenia has not yet been established.
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Affiliation(s)
- Alejandro Borrego-Ruiz
- Departamento de Psicología Social y de las Organizaciones, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain
| | - Juan J. Borrego
- Departamento de Microbiología, Universidad de Málaga, Málaga, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA, Plataforma BIONAND, Málaga, Spain
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2
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Zareifopoulos N, Lagadinou M, Karela A, Kyriakopoulou O, Velissaris D. Neuropsychiatric Effects of Antiviral Drugs. Cureus 2020; 12:e9536. [PMID: 32905132 PMCID: PMC7465925 DOI: 10.7759/cureus.9536] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The adverse events of antiviral drugs are dose-dependent and often reversible. The nervous system is often affected and to date, many studies have been published regarding the central nervous system toxicity of antiviral agents. They may cause significant neuropsychiatric complications, which range from mild symptoms such as irritability and difficulty sleeping to severe complications such as depression, psychosis, and painful peripheral neuropathy, side effects which may necessitate discontinuation of treatment. The pathogenetic mechanisms may involve molecular targets common to other centrally active drugs, including human monoamine oxidase‐A (MAO‐A), serotonin receptors, gamma-aminobutyric acid (GABA) GABA-A receptors, 5-HT2A and 5-HT2C receptors and others. Notable examples include oseltamivir which may act as MAO inhibitor and efavirenz, which has an affinity for serotonin 5-HT2 and GABA-A receptors, the serotonin transporter, the MAO enzyme, and the vesicular monoamine transporter, with subjective effects which may be similar to those of the psychedelic hallucinogen lysergic acid diethylamide (LSD). Other antiviral drugs with prominent nervous system effects include nucleoside reverse transcriptase inhibitors, which are associated with the development of peripheral neuropathy after prolonged use (an effect strongly associated with older drugs which have since fallen into disfavor such as stavudine) and interferons, which may cause depression. Clinicians should be familiar with such adverse effects in order to recognise them promptly once they occur and manage them appropriately.
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Affiliation(s)
| | - Maria Lagadinou
- Emergency Department, General University Hospital of Patras, Patras, GRC
| | - Anastasia Karela
- Emergency Department, General University Hospital of Patras, Patras, GRC
| | | | - Dimitrios Velissaris
- Department of Internal Medicine, University of Patras, School of Health Sciences, Patras, GRC.,Emergency Department, General University Hospital of Patras, Patras, GRC
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3
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Amirsardari Z, Rahmani F, Rezaei N. Cognitive impairments in HCV infection: From pathogenesis to neuroimaging. J Clin Exp Neuropsychol 2019; 41:987-1000. [PMID: 31405320 DOI: 10.1080/13803395.2019.1652728] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Extrahepatic manifestations of hepatitis C virus (HCV) infection, in particular cognitive impairments, can be present in the absence of clinical liver dysfunction. Executive memory, attention, and concentration are cognitive domains that are most frequently affected. Microstructural and functional changes in cortical gray matter and basal ganglia associate these neuropsychiatric changes in early HCV infection. No study has covered the relationship between imaging features of HCV-related cognitive impairment and HCV pathology. Herein we summarize evidence suggesting a direct pathology of HCV in microglia, astrocytes, and microvascular endothelial cells, and a neuroinflammatory response in HCV-related cognitive decline. Lipoproteins and their receptors mediate HCV infectivity in the central nervous system and confer susceptibility to HCV-related cognitive decline. Magnetic resonance spectroscopy has revealed changes compatible with reactive gliosis and microglial activation in basal ganglia, frontal and occipital white matter, in the absence of cirrhosis or hepatic encephalopathy. Similarly, diffusion imaging shows evidence of structural disintegrity in the axonal fibers of white matter tracts associated with temporal and frontal cortices. We also discuss the cognitive benefits and side-effects of the two most popular therapeutic protocols interferon-based therapy and interferon-free therapy using direct acting anti-virals. Evidences support a network-based pattern of disruption in functional connectivity in HCV patients and a common neuronal substrate for HCV-related and interferon-therapy-associated cognitive decline. These evidences might help identify patients who benefit from either interferon-based or interferon-free treatment regimen.
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Affiliation(s)
- Zahra Amirsardari
- Student's Scientific Research Center (SSRC), Tehran University of Medical Sciences , Tehran , Iran.,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| | - Farzaneh Rahmani
- Student's Scientific Research Center (SSRC), Tehran University of Medical Sciences , Tehran , Iran.,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| | - Nima Rezaei
- NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran.,Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences , Tehran , Iran
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4
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Krzeczkowska A, Flowers P, Chouliara Z, Hayes P, Dickson A. 'It's been a long haul, a big haul, but we've made it': hepatitis C virus treatment in post-transplant patients with virus recurrence: An interpretative phenomenological analysis. Health Psychol Open 2018; 5:2055102918792673. [PMID: 30094056 PMCID: PMC6080080 DOI: 10.1177/2055102918792673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
The lived experience of both interferon-based and new interferon-free treatments in patients with hepatitis C virus remains understudied. To explore their journey through hepatitis C virus treatment, we interviewed seven post-transplant patients with recurrent hepatitis C virus. Three themes were identified using interpretative phenomenological analysis. Participants reported an ongoing sense of ontological uncertainty characterized by lack of control over their condition and treatment. Furthermore, an apposition of scepticism and hope accompanying each stage of hepatitis C virus treatment was described. A staged approach to psychological intervention tailored to the needs of the patient and their associated 'stage' of hepatitis C virus treatment was recommended.
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5
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Yoh K, Nishikawa H, Enomoto H, Iwata Y, Kishino K, Shimono Y, Hasegawa K, Nakano C, Takata R, Nishimura T, Aizawa N, Sakai Y, Ikeda N, Takashima T, Ishii A, Iijima H, Matsunaga H, Nakamura H, Nishiguchi S. Comparison of sleep disorders in chronic hepatitis C patients treated with interferon-based therapy and direct acting antivirals using actigraphy. Hepatol Res 2016; 46:1358-1366. [PMID: 26950182 DOI: 10.1111/hepr.12694] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Revised: 03/01/2016] [Accepted: 03/03/2016] [Indexed: 02/08/2023]
Abstract
UNLABELLED This study aimed to compare the severity of sleep problems between chronic hepatitis C (CHC) patients treated with interferon (IFN)-based triple therapy (pegylated [Peg]-IFN plus ribavirin [RBV] plus simeprevir [SMV]) and those who received IFN-free direct-acting antiviral (DAA) therapy. METHODS Our study included 31 patients in group A (Peg-IFN/RBV/SMV combination therapy) and 41 patients in the group B (IFN-free DAA therapy). We prospectively compared the effect of each antiviral treatment regimen on sleep conditions between the two groups adding actigraphy data. Five parameters detected by actigraphy (objective assessment) and scores of the Pittsburgh Sleep Quality Index (subjective assessment, n = 30 [group A] and 35 [group B]) were estimated. The causal effect of each therapy on sleep disturbances was evaluated at baseline and at 4 weeks after commencement of therapy. RESULTS In terms of baseline characteristics, no significant differences between groups were found, except for hepatitis C virus genotype. In group A, sustained virological response 12 rate was 83.9% (26/31), whereas in group B it was 95.1% (39/41). In group A, each score of waking after sleep onset, activity index, wake episodes, and Pittsburgh Sleep Quality Index at 4 weeks significantly increased compared to those evaluated at baseline. In group B, scores of all variables except for sleep episodes at 4 weeks did not significantly change compared to those at baseline. CONCLUSION Interferon-based triple therapy in patients with CHC may cause significant sleep disturbances. Interferon-free DAA therapy is less likely to deteriorate sleep conditions in patients with CHC.
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Affiliation(s)
- Kazunori Yoh
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Hiroki Nishikawa
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Hirayuki Enomoto
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Yoshinori Iwata
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Kyohei Kishino
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Yoshihiro Shimono
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Kunihiro Hasegawa
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Chikage Nakano
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Ryo Takata
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Takashi Nishimura
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Nobuhiro Aizawa
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Yoshiyuki Sakai
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Naoto Ikeda
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Tomoyuki Takashima
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Akio Ishii
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Hiroko Iijima
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Hisato Matsunaga
- Department of Psychiatry, Hyogo College of Medicine, Hyogo, Japan
| | - Hideji Nakamura
- Department of Gastroenterology and Hepatology, Nissay Hospital, Osaka, Japan
| | - Shuhei Nishiguchi
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
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Hepgul N, Pariante CM, Baraldi S, Borsini A, Bufalino C, Russell A, Agarwal K, Cleare AJ, Forton DM, Henderson M, Mondelli V, Ranjith G, Hotopf M. Depression and anxiety in patients receiving interferon-alpha: The role of illness perceptions. J Health Psychol 2016; 23:1405-1414. [PMID: 27458106 DOI: 10.1177/1359105316658967] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Development of psychiatric symptoms during interferon-alpha therapy may be influenced by psychological factors. We examined illness perceptions using the Revised Illness Perceptions Questionnaire in 55 patients with chronic hepatitis C virus infection, due to receive interferon-alpha. The Hospital Anxiety and Depression Scale was used to assess the development of symptoms. Negative identity, consequences and emotional representation beliefs were significantly associated with both higher depression and anxiety scores. Negative illness perceptions play a predictive role in the development of interferon-alpha-induced psychiatric symptoms.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Max Henderson
- 1 King's College London, UK.,2 King's College Hospital, UK
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Coenen M, Hinze AV, Mengel M, Fuhrmann C, Lüdenbach B, Zimmermann J, Dykstra V, Fimmers R, Viviani R, Stingl J, Holdenrieder S, Müller M, Hartmann G, Coch C. Immune- and miRNA-response to recombinant interferon beta-1a: a biomarker evaluation study to guide the development of novel type I interferon- based therapies. BMC Pharmacol Toxicol 2015; 16:25. [PMID: 26392348 PMCID: PMC4578256 DOI: 10.1186/s40360-015-0025-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 09/11/2015] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND The innate immune receptor RIG-I detects viral RNA within the cytosol of infected cells. Activation of RIG-I leads to the induction of antiviral cytokines, in particular type I interferon, the inhibition of a T(H)17 response as well as to the suppression of tumor growth. Therefore, RIG-I is a promising drug target for the treatment of cancer as well as multiple sclerosis. A specific ligand for RIG-I is currently in preclinical testing. The first-in-human trial will need to be carefully designed to avoid an overshooting cytokine response. Therefore, the ResI study was set up to analyze the human immune response to standard treatment with recombinant interferon-beta to establish biomarkers for safety and efficacy of the upcoming first-in-human trial investigating the RIG-I ligand. METHODS/DESIGN ResI is a single center, prospective, open label, non-randomized phase I clinical trial. Three different cohorts (20 healthy volunteers, 20 patients with RRMS and ongoing interferon-beta treatment and 10 patients starting on interferon-beta) will receive standard interferon-beta-1a therapy for nine days. The study will be conducted according to the principles of the german medicinal products act, ICH-GCP, and the Declaration of Helsinki on the phase I unit of the Institute of Clinical Chemistry and Clinical Pharmacology and in the Department of Neurology, both University Hospital Bonn. Interferon-beta-induced cytokine levels, surface marker on immune cells, mRNA- and miRNA-expression as well as psychometric response will be investigated as target variables. DISCUSSION The ResI study will assess biomarkers in response to interferon-β treatment to guide the dose steps within the first-in-human trial with a newly developed RIG-I ligand. Thus, ResI is a biomarker study to enhance the safety of the clinical development of a first-in-class compound. The data can additionally be used for the development of other therapies based on type I interferon induction such as TLR ligands. Moreover, it will help to understand the interferon-beta induced immune response in a controlled in vivo setting in the human system. TRIAL REGISTRATION clinicaltrials.gov ID NCT02364986.
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Affiliation(s)
- Martin Coenen
- Clinical Study Core Unit, Study Center Bonn (SZB), University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
- Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
| | - Annette Viktoria Hinze
- Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.
| | - Martin Mengel
- Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.
| | - Christine Fuhrmann
- Clinical Study Core Unit, Study Center Bonn (SZB), University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
- Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
| | - Bastian Lüdenbach
- Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
| | - Julian Zimmermann
- Deparment of Neurology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
| | - Verena Dykstra
- Clinical Study Core Unit, Study Center Bonn (SZB), University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
- Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
| | - Rolf Fimmers
- Institute of Medical Biometrics, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
| | - Roberto Viviani
- Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany.
| | - Julia Stingl
- Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.
| | - Stefan Holdenrieder
- Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
| | - Marcus Müller
- Deparment of Neurology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
| | - Gunther Hartmann
- Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
| | - Christoph Coch
- Clinical Study Core Unit, Study Center Bonn (SZB), University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
- Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
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Cattie JE, Letendre SL, Woods SP, Barakat F, Perry W, Cherner M, Umlauf A, Franklin D, Heaton RK, Hassanein T, Grant I. Persistent neurocognitive decline in a clinic sample of hepatitis C virus-infected persons receiving interferon and ribavirin treatment. J Neurovirol 2014; 20:561-70. [PMID: 25326107 DOI: 10.1007/s13365-014-0265-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Revised: 05/31/2014] [Accepted: 06/12/2014] [Indexed: 12/26/2022]
Abstract
Treatment of hepatitis C virus (HCV) with pegylated interferon and ribavirin (IFN/RBV) can be associated with neuropsychiatric side effects, which may necessitate dose reductions or treatment discontinuation. This study aimed to characterize the time course and predictors of cognitive and affective/mood symptoms after IFN/RBV treatment initiation. Forty individuals enrolled in a longitudinal project underwent comprehensive cognitive, medical, and psychiatric assessment at baseline and 10 weeks, 6 months, 12 months, and 18 months after treatment initiation. Analyses were conducted to determine the prevalence of neurocognitive impairment over time; explicate the relationship between neurocognitive impairment, neuropsychiatric symptoms, and liver disease at each time point; and identify predictors of neurocognitive decline as well as cognitive effects of viral clearance. By 10 weeks after initiating IFN/RBV, the prevalence of neurocognitive impairment rose from 22.5 to 47.4% (p < 0.05). Infection with genotype 1 and premorbid depression were associated with more severe declines (p < 0.05). After 18 months, 42.5% remained neurocognitively impaired, independent of viral clearance, severity of liver disease, and current depressive symptoms. Undetectable viral load was not associated with improvement 18 months after initiating treatment (p > 0.10). Results of the current study indicate that IFN/RBV treatment-emergent neurocognitive declines are significant, prevalent, and may persist long after treatment cessation. Clinicians should monitor cognition throughout the course of treatment for HCV, noting that early declines may indicate individuals at elevated risk for persistent neurocognitive impairment. Longer-term studies are needed to determine whether lasting declines may remit over longer intervals or with newer direct acting agents.
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Affiliation(s)
- Jordan E Cattie
- University of California, San Diego, Translational Methamphetamine AIDS Research Center, San Diego, CA, USA
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9
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Dell'Osso B, Prati G, Palazzo MC, Rumi MG, Cavallaro F, Aghemo A, Colombo M, Altamura AC. Predictors of psychopathological outcome during peg-interferon and ribavirin therapy in patients with chronic HCV-correlated hepatitis. J Interferon Cytokine Res 2012; 33:9-14. [PMID: 23276143 DOI: 10.1089/jir.2012.0060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Peg-interferon (Peg-IFN) and ribavirin (RBV) therapy is reported to induce psychiatric symptoms and syndromes in 20% of patients treated for Hepatitis C Virus (HCV) infection. Present study was aimed to quantify the phenomenon and assess the influence of psychiatric counseling over antiviral completion rate and the use of psychometric tools, in terms of prediction of psychopathological outcome. Ninety-six HCV patients were assessed, before antiviral treatment, by means of the Sheehan Disability Scale (SDS), Mood Disorder Questionnaire (MDQ), Symptom Checklist-90, and Internal State Scale (ISS). Sociodemographic and clinical variables and completion rate were collected. Binary logistic regression was performed to evaluate whether scores were predictive of psychiatric visit, development of psychiatric disorders, and need for treatment. Ninety-five patients (99%) completed antiviral treatment; 27 subjects (29%) needed psychiatric visit: among them, mood disorder was diagnosed in 15 (16%) and were pharmacologically treated. Baseline SDS and MDQ higher scores were found to be predictive of psychiatric visit [odds ratio (OR)=1.258, P<0.001 and OR=1.425, P=0.05, respectively]. Furthermore, higher MDQ score (P=0.017) and ISS hostility scores (OR=1.048, P=0.014) at baseline predicted the subsequent development of mood episodes, while ISS activation correlated negatively (OR=0.948, P=0.009). Finally, the need for treatment was predicted by higher scores at the MDQ and ISS activation items (OR=2.467, P=0.030; OR=0.970, P=0.038). Present findings suggest that psychiatric counseling may be needed in almost 30% of HCV patients on antiviral treatment, with positive influence over the completion rate. Baseline higher scores at psychometric questionnaires-MDQ-in particular, predictors of psychopathological outcome during Peg-IFN and RBV therapy in patients with chronic HCV-correlated hepatitis reflecting individual functioning before starting antiviral therapy and positive history for mood disorders, seem to predict psychiatric visit, onset of mood episodes, and need for psychopharmacological treatment. Further investigation is warranted to confirm results.
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Affiliation(s)
- Bernardo Dell'Osso
- Department of Psychiatry, Fondazione IRCSS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
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10
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Simón-Talero M, Buti M, Esteban R. Severe anaemia related to oseltamivir during treatment of chronic hepatitis C: a new drug interaction? J Viral Hepat 2012; 19 Suppl 1:14-7. [PMID: 22233409 DOI: 10.1111/j.1365-2893.2011.01521.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Treatment for hepatitis C virus is often complicated by anaemia from ribavirin-related haemolysis and bone marrow suppression because of peginterferon alfa. An extensive literature search revealed no reports of drug interactions between ribavirin and oseltamivir. We report the case of a patient with chronic hepatitis C infection who developed severe anaemia during antiviral treatment with peginterferon alfa/ribavirin when oseltamivir was added to treat influenza. The adverse events related to ribavirin and drug-drug interactions during therapy for hepatitis C are discussed.
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Affiliation(s)
- M Simón-Talero
- Liver Unit, Hospital Universitari Vall d'Hebron, Department of Medicine, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Barcelona, Spain
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Calvaruso V, Mazza M, Almasio PL. Pegylated-interferon-α(2a) in clinical practice: how to manage patients suffering from side effects. Expert Opin Drug Saf 2011; 10:429-35. [PMID: 21323500 DOI: 10.1517/14740338.2011.559161] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
INTRODUCTION The goal of antiviral therapy in patients with chronic hepatitis C is to slow or halt the progression of fibrosis and prevent the development of cirrhosis. Accordingly, antiviral treatment is proposed for a large population of patients with chronic hepatitis. AREAS COVERED The standard-of-care for chronic hepatitis C is the combination of pegylated IFN (PEG-IFN) and ribavirin. The use of these drugs has been correlated with a range of adverse effects, including influenza-like symptoms, hematological changes and neuropsychiatric disturbances. The effects of these adverse events associated with PEG-IFN therapy are manifold and are a major reason why patients decline or stop therapy. This review addresses the screening for adverse event risk factors and guides the patient to success with adherence strategies. EXPERT OPINION Knowledge of the side effects correlated with PEG-IFN is very relevant for clinicians because it can allow them to arrange the best methods for treating these effects and avoid the discontinuation of antiviral treatment. Moreover, the use of new antiviral drugs will considerably shorten treatment periods reducing many of the above-described side effects and, thus, increase adherence to scheduled therapy.
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Affiliation(s)
- Vincenza Calvaruso
- University of Palermo, Gastroenterology & Hepatology Unit, Dipartimento Biomedico di Medicina Interna e Specialistica, Piazza delle Cliniche, 2, 90127 Palermo, Italy
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12
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Optimization of an induction strategy for improving interferon-α2b production in the periplasm ofEscherichia coliusing response surface methodology. Biotechnol Appl Biochem 2010; 56:141-50. [DOI: 10.1042/ba20100104] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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13
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Wobrock T, Mihm U, Löhr C, Hofmann WP, Sarrazin C, Zeuzem S, Falkai P. Cognition in hepatitis C patients treated with pegylated interferon. World J Biol Psychiatry 2010; 10:819-26. [PMID: 19995219 DOI: 10.1080/15622970701714362] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Neuropsychiatric symptoms are frequently reported by patients with chronic hepatitis C during treatment with interferon (IFN)-alpha and may lead to treatment discontinuation. In order to assess the objective neuropsychiatric impairments we prospectively administered standardized neuropsychological testing before and 3 months after the initiation of antiviral treatment with pegylated IFN-alpha in 17 patients suffering from chronic hepatitis C. In addition depression and anxiety scores, social functioning and hepatological parameters were obtained. While depressive and anxiety symptoms increased significantly during treatment only subtle worsening in neurocognitive performance could be detected, indicating slight impairment in cognitive flexibility and psychomotor speed (Trail Making Test B; 69.6+/-23 s before vs. 80.7+/-31 s during therapy, P=0.011, not remaining significant after Bonferroni correction). We found no association between reduced neurocognitive performance and the severity of depression. Better neurocognitive performance in single domains was associated with better response to antiviral treatment measured as the decline of elevated liver enzymes (AST). We conclude that neurocognitive performance was influenced by antiviral IFN-alpha-based combination treatment only in single domains and not to a clinically relevant extent in contrast to the significant worsening of depression.
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Affiliation(s)
- Thomas Wobrock
- Department of Psychiatry and Psychotherapy, Georg-August University Göttingen, Göttingen, Germany.
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Prospective analysis of depression during peginterferon and ribavirin therapy of chronic hepatitis C: results of the Virahep-C study. Am J Gastroenterol 2009; 104:2949-58. [PMID: 19789525 DOI: 10.1038/ajg.2009.528] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Combination therapy for chronic hepatitis C is associated with depression, which may lead to worse treatment outcomes. The objectives of this study were to determine the association between patient characteristics and depression before and during treatment and to evaluate the relationship between depression and treatment outcomes. METHODS Prospective data from the Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (Virahep-C) study were analyzed (191 African Americans, 203 Caucasians). Depression was defined as a score of >23 on the Center for Epidemiologic Studies Depression (CES-D) scale. Scores were taken before treatment, at weeks 4, 12, and 24 of treatment, and 24 weeks after treatment ended. Baseline social support was measured using the Medical Outcomes Study (MOS) Social Support Survey. Associations between baseline patient characteristics and incident depression were assessed with discrete-time Cox proportional hazards models. RESULTS At baseline, 47 (12%) participants had CES-D scores 23. Univariable analyses indicated that several patient characteristics were associated with baseline depression, including lower social support (P<0.0001). On treatment, these patients were more likely to have psychiatric adverse events (AEs) or start new antidepressants (45 vs. 28%, P=0.02) and to have had early treatment discontinuation (38 vs.13%, P<0.0001); however, sustained virological response (SVR) rates were similar (38 vs. 40%, P=0.79) to those of participants without baseline depression. The incidence of new-onset depression was 26% by 24 weeks. One-third of patients were started on antidepressants, and no patients attempted suicide. Multivariable analyses indicated that new-onset depression was significantly associated with younger age (P=0.04), lower social support (P<0.001), and "feeling depressed, sad, or blue" (P=0.008). Patients who developed depression during treatment were more likely to have a psychiatric AE or begin antidepressants (44 vs. 23%, P<0.001) but had lower rates of treatment discontinuation (6 vs. 15%, P=0.02) and comparable rates of SVR compared with patients without depression (47 vs. 38%, P=0.16). There were no differences in the frequency of pretreatment or new-onset depression between African-American and Caucasian participants in this study. CONCLUSIONS In this large prospective analysis, baseline and new-onset depression were associated with patient characteristics and treatment outcomes; however, SVR rates did not differ between depressed and nondepressed patients. The relationship of lower baseline social support with depressive symptoms warrants further investigation.
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Fontana RJ, Kronfol Z, Lindsay KL, Bieliauskas LA, Padmanabhan L, Back-Madruga C, Lok AS, Stoddard AM, the HALT-C Trial Group. Changes in mood states and biomarkers during peginterferon and ribavirin treatment of chronic hepatitis C. Am J Gastroenterol 2008; 103:2766-75. [PMID: 18721241 PMCID: PMC3712502 DOI: 10.1111/j.1572-0241.2008.02106.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Depression is a frequent side effect of interferon therapy in patients with chronic hepatitis C (CHC). The aim of this study was to identify baseline and on-treatment predictors of depression in CHC patients receiving peginterferon and ribavirin. METHODS In total, 201 prior nonresponders with advanced fibrosis were treated with peginterferon alfa-2a and ribavirin for 24 wk in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial. Of these, 74 continued on antiviral therapy through week 48. Mood states were assessed with the Beck Depression Inventory II and the Composite International Diagnostic Interview. Plasma cortisol and whole blood serotonin levels were measured in 101 subjects at weeks 0, 4, 24, 48, and 72. RESULTS The incidence of interferon-induced depression was 23% and 42% at weeks 24 and 48, respectively. Although 22% of patients had baseline depression, the absence of a week 20 virological response was the only independent predictor of interferon-induced depression at week 24 (P = 0.0009). Plasma cortisol levels did not change during treatment nor correlate with depression. In contrast, whole blood serotonin/platelet levels significantly decreased during treatment, but did not correlate with interferon-induced depression through week 24 (P = 0.35), nor through week 48 (P = 0.51). CONCLUSION Depression during peginterferon and ribavirin therapy was associated with a lower antiviral response. The significant reduction in whole blood serotonin levels over time suggest that further studies of the serotonergic pathway are warranted to identify the mediators of interferon-induced depression.
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Affiliation(s)
| | - Ziad Kronfol
- Department of Psychiatry, University of Michigan, Ann Arbor, MI
| | - Karen L. Lindsay
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Linas A. Bieliauskas
- Department of Psychiatry, University of Michigan, Ann Arbor, MI,Psychology Service, Veterans Affairs Health System, Ann Arbor, MI
| | | | - Carla Back-Madruga
- Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Anna S.F. Lok
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI
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16
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Tsao CW, Lin YS, Cheng JT, Lin CF, Wu HT, Wu SR, Tsai WH. Interferon-alpha-induced serotonin uptake in Jurkat T cells via mitogen-activated protein kinase and transcriptional regulation of the serotonin transporter. J Psychopharmacol 2008; 22:753-60. [PMID: 18308792 DOI: 10.1177/0269881107082951] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Interferon (IFN)-alpha upregulates serotonin (5-HT) uptake and serotonin transporter (5-HTT) messenger ribonucleic acid (mRNA) expression in immune cells, which implies the mechanism underlying IFN-alpha-induced depression. However, the signal transduction of this effect remains unclear. We investigated whether the effects of IFN-alpha on the functions of 5-HTT were related to mitogen-activated protein kinase (MAPK). By performing Western blotting, real-time reverse transcriptase-polymerase chain reaction and [3H]5-HT labelling, we examined MAPK phosphorylation, 5-HTT mRNA expression and 5-HT uptake in Jurkat T cells. The cells had been cultured for different time periods (1) with IFN-alpha alone and (2) preincubated with either MAPK inhibitors or with the selective serotonin reuptake inhibitor, fluoxetine, and subsequently cultured along with IFN-alpha. The levels of MAPK phosphorylation, 5-HTT mRNA expression and 5-HT uptake all increased in the IFN-alpha-treated cells but were blocked in those that were pretreated with MAPK inhibitors and fluoxetine. These results appear to clarify the association of depression with IFN-alpha-induced 5-HT uptake that reduces the 5-HT levels and IFN-alpha-regulated transcription of 5-HTT; further, the results suggest the involvement of MAPK in this process.
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Affiliation(s)
- C-W Tsao
- Department of Nursing, Chung Hwa University of Medical Technology, Tainan County, Taiwan.
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17
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Psychiatric symptoms during interferon treatment for hepatitis C: experiences from a tertiary care hepatology centre. Aliment Pharmacol Ther 2008; 27:1071-80. [PMID: 18266996 DOI: 10.1111/j.1365-2036.2008.03640.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Most research on the psychiatric symptoms of peginterferon/ribavirin for the treatment of hepatitis C comes from VA centres and clinical trials with rigid entry criteria that often excluded patients with markers of mental health and substance use disturbance (MH/SUD). The findings from these lines of research may not be generalizable to patients treated under standard of care in a tertiary care setting. AIM To investigate the incidence and outcomes of psychiatric symptoms in patients treated under standard of care protocol, not enrolled in clinical trials. METHODS This is a retrospective analysis of 215 patients who underwent therapy from 2002 to 2006 at a university-based tertiary care centre. Survival curves explored the relationship between history of MH/SUD and the development of psychiatric symptoms on treatment. RESULTS The cumulative history of MH/SUD was 67%. Of these, 39% had taken psychotropic medications previously, and 80% continued on them during therapy. On therapy, 46% developed depressive symptoms, 19% and 46% endorsed anxiety and irritability respectively. Cumulatively, 64% of patients indicated mood disturbance on therapy. Most symptoms developed between weeks 2 and 18, and rarely after week 20. Of those who developed mood symptoms, 66% required an intervention. Treatment discontinuation was infrequent. CONCLUSIONS This large observational study provides important insights into the incidence and course of psychiatric symptoms in an unselected sample of patients treated in a tertiary care setting. Patients had higher rates of MH/SUD comorbidity, psychotropic medication use and exhibit higher rates of mood disturbance on therapy compared with previous reports, although a majority completed the prescribed treatment regimen.
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18
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Abstract
A disease whose reputation is often worse than its reality, hepatitis C is usually benign. Most infected individuals do not experience symptoms requiring treatment, and roughly half of those treated will become free of detectable virus for an extended, perhaps permanent, period. Moreover, a growing body of data suggests that drug users can attain successful treatment outcomes, even when not completely abstinent. Addiction professionals belong in the forefront of prevention and management of this disease. We can assist our patients by helping them stabilize their lifestyles, correcting misperceptions about the disease, teaching prevention and health maintenance, promoting access to diagnosis and treatment, monitoring for treatment side effects, and providing encouragement to remain in treatment.
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Fontanges T, Beorchia S, Douvin C, Delassalle P, Combis JM, Hanslik B, Jacques JP, Filoche B, Desmorat H, Chandelier C, Ouzan D. Safety and efficacy of combination therapy with peginterferon alfa-2a (40kD) and ribavirin in the outpatient setting: prospective analysis of 197 patients with chronic hepatitis C viral infection. ACTA ACUST UNITED AC 2007; 31:566-72. [PMID: 17646782 DOI: 10.1016/s0399-8320(07)89432-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
OBJECTIVES Combination therapy using peginterferon alfa-2a (40 kD) plus ribavirin achieves viral eradication in nearly 60% of patients with chronic hepatitis C viral infection. However, because of the numerous side effects, use of the combination regimen might be restricted for patients consulting private practitioners specialized in hepatogastroenterology. PATIENTS AND METHOD Conducted in this specific context, this prospective clinical trial investigated the safety and efficacy of combination therapy in 197 patients. Therapy was given in compliance with the recommendations of the French consensus conference on hepatitis C treatment. RESULTS Commonly reported adverse effects were noted in 90% of patients, most occurring during the first three months, with a stable prevalence thereafter and resolution after treatment end. The most frequent adverse events were asthenia (35 to 37.5% according to the treatment group pruritus (25 to 26.3%) and flu-like syndrome (19 to 21.7%). A depressive syndrome was reported in 20 to 21% of patients. Grade 4 neutropenia was exceptional and never led to severe infections. At intent-to-treat analysis, the rate of sustained virological response was 54.8% for the entire population. It was 71.1% for patients with genotypes 2 or 3 (mainly treated for 24 weeks) and 44.6% for patients with genotype 1 (all treated 48 weeks). CONCLUSION The characteristic features of combination therapy observed in the context of private hepatogastroenterology consultations are similar to those observed in randomized clinical trials.
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20
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Fontana RJ, Bieliauskas LA, Lindsay KL, Back-Madruga C, Wright EC, Snow KK, Lok ASF, Kronfol Z, Padmanabhan L. Cognitive function does not worsen during pegylated interferon and ribavirin retreatment of chronic hepatitis C. Hepatology 2007; 45:1154-63. [PMID: 17465000 DOI: 10.1002/hep.21633] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED Treatment of chronic hepatitis C with pegylated interferon (peginterferon) and ribavirin can cause or exacerbate depression but its effects on cognitive function are largely unknown. The aim of this study was to determine whether treatment with peginterferon and ribavirin adversely impacts cognitive function in patients with chronic hepatitis C. Prior nonresponders to interferon were retreated with peginterferon alfa-2a and ribavirin for 24 (n=177) or 48 weeks (n=57) in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial. Cognitive function was prospectively assessed using a battery of 10 standardized neuropsychological tests at weeks 0, 24, 48, and 72. Cognitive impairment was defined based upon a global deficit score. The Beck Depression Inventory and Brief Symptom Inventory were used to assess mood status. The 57 subjects who completed 48 weeks of antiviral therapy reported significant increases in difficulty concentrating, emotional distress, and symptoms of depression, all of which improved after cessation of therapy [P<0.0001, analysis of variance (ANOVA)]. Nonetheless, the frequency of cognitive impairment did not increase during the first 24 weeks of treatment in 177 patients (34% versus 32%, P=0.64) nor in the 57 patients completing 48 weeks of treatment (P=0.48, ANOVA). CONCLUSION Retreatment of prior non-responders with peginterferon and ribavirin was not associated with objective evidence of cognitive impairment as measured by a comprehensive battery of neuropsychological tests. The lack of cognitive impairment is reassuring and suggests that self-reported symptoms of cognitive dysfunction are more likely related to the systemic and psychiatric side effects of antiviral treatment rather than measurable changes in cognition.
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Affiliation(s)
- Robert J Fontana
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0362, USA.
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21
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Tsao CW, Lin YS, Cheng JT, Chang WW, Chen CL, Wu SR, Fan CW, Lo HY. Serotonin transporter mRNA expression is decreased by lamivudine and ribavirin and increased by interferon in immune cells. Scand J Immunol 2006; 63:106-15. [PMID: 16476009 DOI: 10.1111/j.1365-3083.2005.01715.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Clinical reports document that depression as a side effect is more prevalent in hepatic patients given interferon (IFN)-alpha therapy than in those given lamivudine. The mechanisms, however, are poorly understood. Serotonin transporter (5-HTT), via uptake of serotonin (5-HT) into presynaptic serotoninergic neurons, is an initial action site for antidepressants. Real-time polymerase chain reaction (PCR) was used to quantify 5-HTT mRNA expression in immune cells in order to evaluate whether 5-HTT acted as an indicator of depression. Results showed that the 5-HTT mRNA expression was much higher in T-cell and B-cell lines than that in a monocytic cell line. Treatment with either lamivudine or ribavirin reduced the 5-HTT mRNA expression, protein level and 5-HT uptake in T-cell line. Treatment with IFN-alpha, however, increased those levels in the same group. A similar effect was observed in peripheral blood mononuclear cells (PBMC). Mimicking clinical use by treating PBMC with a combination of IFN-alpha and ribavirin increased the 5-HTT mRNA expression level. Our study indicates that these therapeutic drugs regulate 5-HTT expression, which implies that 5-HTT might be a trait marker in IFN-alpha-induced depression after hepatic therapy.
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Affiliation(s)
- C-W Tsao
- Department of Nursing, Chung Hwa College of Medical Technology, Tainan County, Taiwan.
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22
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Abstract
The complications of chronic hepatitis C virus infection can be prevented by antiviral therapy. The initial choice of interferon alfa and, subsequently, ribavirin as potential treatments for chronic hepatitis C was empirical. Nevertheless, the combination of pegylated interferon alfa and ribavirin has become the standard treatment of chronic hepatitis C. Since the advent of interferon-based therapy, enormous progress has been made in understanding the mechanisms of treatment efficacy and failure, and in everyday patient management. The principal advances are: a better understanding of hepatitis C virus steady-state kinetics and the antiviral mechanisms of interferon and ribavirin; easier treatment decisions thanks to novel assays to assess liver disease severity and the virological characteristics of infection; a better use of virological tests to tailor therapy; a better management of adverse effects; a better understanding of virological treatment failure; and a better management of "special" populations, including patients with decompensated cirrhosis and end-stage liver disease, liver transplant recipients, hemodialysis patients and renal transplant recipients, human immunodeficiency virus-coinfected patients, intravenous drug users and patients on opiate replacement therapy, or virological non responders to previous therapies. Steady-state HCV kinetics offers several potential targets for new drugs. These targets should ideally be hit simultaneously in order to achieve viral eradication within a reasonable time frame. Future drugs for HCV infection will belong to four main categories, including new interferons, alternatives to ribavirin, specific HCV inhibitors, and immune modulators. New treatments and vaccines might make it possible to eradicate HCV in the future.
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23
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Shiffman ML. Chronic hepatitis C: treatment of pegylated interferon/ribavirin nonresponders. Curr Gastroenterol Rep 2006; 8:46-52. [PMID: 16510034 DOI: 10.1007/s11894-006-0063-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
Patients with chronic hepatitis C virus (HCV) who were nonresponders to previous treatment with pegylated interferon and ribavirin are a growing population. The vast majority have genotype 1, a high viral load, advanced fibrosis or cirrhosis, and are of African-American race. The evaluation of these patients should include a thorough review of the previous treatment record and characterization of the previous nonresponse. Patients with prior null response are likely resistant to the effects of interferon. In contrast, patients with partial virologic response, breakthrough, and relapse could potentially achieve sustained virologic response if one or more correctable factors that contributed to the prior nonresponse are identified and addressed before and during retreatment. Many HCV nonresponders, especially those with no fibrosis or mild fibrosis, have an excellent prognosis, are at low risk to develop cirrhosis, and should simply be monitored at periodic intervals until more effective therapy has been developed.
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Affiliation(s)
- Mitchell L Shiffman
- Hepatology Section, Virginia Commonwealth University Medical Center, Box 980341, Richmond, VA 23298, USA.
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24
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Schäfer A, Scheurlen M, Felten M, Kraus MR. Physician-patient relationship and disclosure behaviour in chronic hepatitis C in a group of German outpatients. Eur J Gastroenterol Hepatol 2005; 17:1387-94. [PMID: 16292094 DOI: 10.1097/00042737-200512000-00019] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
OBJECTIVES In chronic hepatitis C infection, the doctor-patient relationship can be burdened for various reasons. Factors associated with the doctor-patient relationship and self-disclosure of hepatitis C virus (HCV) status have not so far been investigated systematically. The goal of the study was to examine self-disclosure of HCV positivity, perceived stigmatization, and potential predictor variables in a German outpatient group. METHODS In a cross-sectional single-centre study, we included a volunteer sample of 103 HCV outpatients. Patient recruitment was between March 2003 and September 2004. Data were obtained from a fully standardized face-to-face interview [HCV disclosure behaviour (main interview variable), stigmatization, doctor-patient relationship] and psychometric self-assessment questionnaires [Hospital Anxiety and Depression Scale, German version; Symptom Checklist-90 Revised (global severity index); Inventory of Interpersonal Problems (total score)]. RESULTS The overall general disclosure rate was 44.7% (with respect to all physicians). However, 75% stated revealing their positive serostatus in future physician appointments (P < 0.05). With respect to family/friends, disclosure rates were clearly higher (permanent partner, 99%; average, 76.7%). Patients' disclosure behaviour could not be predicted by sociodemographic variables or personality factors (binary logistic regression, P > 0.05). Similarly, the Hospital Anxiety and Depression Scale and Symptom Checklist-90 subscales were not substantially associated with HCV disclosure. Experiences of stigmatization (rate 38.8%) were more frequent in women (P = 0.014) and patients with higher depression scores (P = 0.029). CONCLUSIONS There is a need for education in the field of chronic hepatitis C in order to improve the physician-patient relationship. HCV disclosure rates might thus be increased and the frequency of problematic contacts reduced. Importantly, the data show that physicians should explicitly ask for the patients' HCV status because unrequested disclosure cannot be taken for granted.
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Affiliation(s)
- Arne Schäfer
- Medizinische Klinik und Poliklinik II, Würzburg University, Department of Gastroenterology and Hepatology, Germany.
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25
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Sylvestre DL, Litwin AH, Clements BJ, Gourevitch MN. The impact of barriers to hepatitis C virus treatment in recovering heroin users maintained on methadone. J Subst Abuse Treat 2005; 29:159-65. [PMID: 16183464 DOI: 10.1016/j.jsat.2005.06.002] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2004] [Revised: 11/01/2004] [Accepted: 11/10/2004] [Indexed: 01/16/2023]
Abstract
Although most cases of hepatitis C virus (HCV) infection are associated with injection drug use, there are few data regarding the impact of putative barriers such as psychiatric disease and intercurrent drug use on HCV treatment outcomes. To define the impact of characteristics often cited as reasons for withholding HCV treatment, we studied HCV treatment in a real world sample of 76 recovering heroin users maintained on methadone. Overall, 21 (28%) had a sustained virological response and 18 (24%) discontinued treatment early. Although there was a modest decrement in response rates in patients reporting a preexisting psychiatric history (p = .01), neither intercurrent drug use nor short duration of pretreatment drug abstinence led to significant reductions in virological outcomes (p = .09 and p = .18, respectively.) We conclude that injection drug users can be safely and effectively treated for HCV despite multiple barriers to treatment when they are treated in a setting that can address their special needs.
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Affiliation(s)
- Diana L Sylvestre
- Department of Medicine, University of California, San Francisco, CA, USA.
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26
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Kendirli T, Kismet E, Demirkaya E, Aydin HI, Kesik V, Köseoğlu V. Death possibly associated with interferon use in a patient with chronic hepatitis. Acta Paediatr 2005; 94:984-5. [PMID: 16188832 DOI: 10.1111/j.1651-2227.2005.tb02028.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Kraus MR, Schäfer A, Csef H, Scheurlen M. Psychiatric side effects of pegylated interferon alfa-2b as compared to conventional interferon alfa-2b in patients with chronic hepatitis C. World J Gastroenterol 2005; 11:1769-74. [PMID: 15793861 PMCID: PMC4305871 DOI: 10.3748/wjg.v11.i12.1769] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess systematically the spectrum and extent of depressive symptoms comparing patient groups receiving peginterferon or conventional interferon.
METHODS: Ninety-eight patients with chronic hepatitis C and interferon-based therapy (+ribavirin) were consecutively enrolled in a longitudinal study. Patients were treated with conventional interferon alfa-2b (48/98 patients; 5 MIU interferon alfa-2b thrice weekly) or peginterferon alfa-2b (50/98 patients; 80-150 μg peginterferon alfa-2b) in combination with weight-adapted ribavirin (800-1200 mg/d). Repeated psychometric testing was performed before, three times during and once after antiviral therapy: Depression was evaluated by the Hospital Anxiety and Depression Scale (HADS), anger/hostility by the Symptom Checklist-90 Items Revised (SCL-90-R).
RESULTS: Therapy with pegylated interferon alfa-2b produces comparable scores for depression (ANOVA: P = 0.875) as compared to conventional interferon. Maximums of depression scores were even higher and cases of clinically relevant depression were frequent during therapy with peginterferon. Scores for anger/hostility were comparable for both therapy subgroups.
CONCLUSION: Our findings suggest that the extent and frequency of depressive symptoms in total are not reduced by peginterferon. Monitoring and management of neuropsychiatric toxicity especially depression have to be considered as much as in antiviral therapy with unmodified interferon.
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Affiliation(s)
- Michael-R Kraus
- Medizinische Poliklinik, University of Wurzburg, Klinikstr 6 - 8, D-97070 Würzburg, Germany.
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Castéra L, Constant A, Henry C, Couzigou P. Manifestations psychiatriques au cours du traitement de l’hépatite chronique C. ACTA ACUST UNITED AC 2005; 29:123-33. [PMID: 15795658 DOI: 10.1016/s0399-8320(05)80714-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Laurent Castéra
- Service d'Hépato-Gastroentérologie, Hôpital Haut-Lévêque, Pessac.
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30
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Hilsabeck RC, Hassanein TI, Ziegler EA, Carlson MD, Perry W. Effect of interferon-alpha on cognitive functioning in patients with chronic hepatitis C. J Int Neuropsychol Soc 2005; 11:16-22. [PMID: 15686604 DOI: 10.1017/s1355617705050022] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2003] [Revised: 07/09/2004] [Indexed: 01/18/2023]
Abstract
Treatment with interferon-alpha (IFN-alpha) has been shown to adversely affect cognitive functioning in patients with a variety of medical disorders, but information about the effects of IFN-alpha on cognitive functioning in patients with chronic hepatitis C (CHC) is limited. The purpose of this study was to examine the effects of IFN-alpha on neuropsychological test performance in CHC patients. Participants were 30 patients with CHC, 11 who underwent IFN-alpha therapy and 19 who did not. All participants were tested at baseline (i.e., pretreatment) and approximately 6 months later with the Symbol Digit Modalities Test and Trail Making Test. Results revealed that the treatment group performed significantly worse than untreated CHC patients on Part B of the Trail Making Test after approximately 6 months of treatment. No significant group differences were found on Part A of the Trail Making Test or Symbol Digit Modalities Test. Findings suggest that CHC patients undergoing treatment with IFN-alpha may experience reduced abilities to benefit from practice but suffer no decrements in performance after 6 months of treatment. Additional research is needed to replicate these findings and to explore risk factors for susceptibility to IFN-alpha-induced effects.
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Affiliation(s)
- Robin C Hilsabeck
- Department of Neuropsychiatry & Behavioral Science, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
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31
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Abstract
Nearly 4 million people in the United States have evidence of hepatitis C infection (HCV), representing a significant cause of cirrhosis and liver cancer as well a major burden to our healthcare systems and society. Antiviral therapy can successfully eradicate HCV over the long term, potentially reducing the risk of progression and improving patients' quality of life. The currently preferred HCV treatment is a combination of pegylated interferon alfa and ribavirin, which can achieve an overall sustained viral eradication rate of 55%. The duration of this treatment is typically determined by HCV genotype and the patient's early virologic response to the antiviral regimen. Evidence has accumulated over the past few years to indicate that close adherence to the optimal antiviral regimen can enhance sustained virologic response. But optimal treatment outcomes require diligence and careful management of side effects related to combination therapy. Although reducing the dose of pegylated interferon alfa, ribavirin, or both can effectively treat side effects, suboptimal doses of this regimen, especially ribavirin, may negatively affect virologic response. An alternative strategy is to use growth factors to treat cytopenias. This strategy can obviate dose reductions while potentially improving patients' quality of life. Patient support seems especially important early after the initiation of antiviral therapy. Encouraging study findings involving the growth factors, epoetin alfa and darbepoetin alfa, suggest improved anemia and quality of life while maintaining the optimal ribavirin dose. Future work should be aimed at providing stronger evidence for the use of these "supportive products" during anti-HCV therapy. As we strive to develop better treatment options for our HCV patients, the importance of adhering to the treatment regimen continues to play a central role. Effective side effect management is crucial for the success of this treatment because adherence is negatively affected by side effects related to the antiviral regimen. By identifying and addressing the important side effects of combination therapy for HCV, adherence to treatment can be improved and optimal outcomes can be achieved.
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Affiliation(s)
- Brian P Mulhall
- Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA 22042, USA
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Häuser W, Zimmer C, Schiedermaier P, Grandt D. Biopsychosocial predictors of health-related quality of life in patients with chronic hepatitis C. Psychosom Med 2004; 66:954-8. [PMID: 15564364 DOI: 10.1097/01.psy.0000145824.82125.a8] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To assess biopsychosocial predictors of health-related quality of life (HRQOL) in patients with chronic hepatitis C. METHODS In 94 consecutive patients with chronic hepatitis C attending a liver center, HRQOL was assessed by the Medical Outcome Study Short Form Health Survey 36 (SF-36) and by the German version of the Chronic Liver Disease Questionnaire. The predictive effect on HRQOL of disease-related worries measured by the worry subscale of the Chronic Liver Disease Questionnaire, psychiatric comorbidity (defined by at least one Hospital Anxiety and Depression Scale German Version Score > or =11), the Child-Pugh score in case of cirrhosis, interferon therapy, and active medical comorbidities was assessed by a multiple regression analysis. RESULTS From 88 patients (age, 48.6 +/- 14.6 years; 50% female), 62 (70%) had no cirrhosis, 15 (17%) Child A, 5 (6%) Child B, and 6 patients (7%) Child C cirrhosis. The mental summary score of SF-36 was predicted by the amount of disease-related worries (corrected R2 = 0.33; beta = 3.2; p < .001) and psychiatric comorbidity (corrected R2 = 0.42; beta = -9.0; p < .001), by the physical summary score of SF-36 by the amount of disease related worries (corrected R2 = 0.33; beta = 4.0; p < .001), and by the number of active medical comorbidities (corrected R2 = 0.39; beta = -2.0; p = .006). CONCLUSIONS The HRQOL in chronic hepatitis C is not determined by the severity of the liver disease but by psychiatric and medical comorbidities and disease-related worries.
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Affiliation(s)
- Winfried Häuser
- Department of Internal Medicine I, Klinikum Saarbrücken gGmbH, Winterberg 1,D-66119 Saarbruecken, Germany.
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Getachew Y, Browning JD, Prebis M, Rogers T, Brown GR. Combination therapy for the treatment of hepatitis C in the veteran population: higher than expected rates of therapy discontinuation. Aliment Pharmacol Ther 2004; 20:629-36. [PMID: 15352911 DOI: 10.1111/j.1365-2036.2004.02095.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
AIM To compare the efficacy of high-dose induction with standard dose interferon therapy for the treatment of chronic hepatitis C virus at the Dallas Veterans Affairs Medical Center. METHODS Patients were randomized to receive 5 million units daily interferon-alpha2b for 4-weeks followed by 44-weeks for genotype 1 or 20 weeks for non-genotype 1 of standard dose therapy (3 million units three times a week) or standard dose therapy for total treatment duration. Daily weight-based ribavirin was used for entire therapy interval. RESULTS Forty-five patients were enrolled in the trial with genotype 1 comprising 75.6% of the sample. Cirrhosis or bridging-fibrosis was present in 69% of the patients. Of the 29 liver biopsies available for Knodell scoring, 41% and 51% had scores of 6-10 and 11-15, respectively. Rates of sustained virological response did not differ significantly between the two treatment groups. Therapy type and/or early intervention for depression did not affect the rate of therapy discontinuation, which was 26.6%. CONCLUSION The rate of sustained virological response was similar between the two treatment groups and higher than anticipated among patients with cirrhosis or bridging-fibrosis. The rate of therapy discontinuation was also higher than anticipated but was not attributable to therapy type or untreated depression.
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Affiliation(s)
- Y Getachew
- Department of Internal Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center at Dallas, USA
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Laguno M, Blanch J, Murillas J, Blanco JL, León A, Lonca M, Larrousse M, Biglia A, Martinez E, García F, Miró JM, de Pablo J, Gatell JM, Mallolas J. Depressive Symptoms after Initiation of Interferon Therapy in Human Immunodeficiency Virus-Infected Patients with Chronic Hepatitis C. Antivir Ther 2004. [DOI: 10.1177/135965350400900604] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background Interferon alpha (IFN-α) therapy for chronic hepatitis C (CHC) infection is commonly associated with neuropsychiatric side effects including depressive symptomatology. In this study, we evaluated the incidence and management of depressive symptoms during IFN-α therapy in HIV-infected patients with CHC. Methods HIV-infected patients with CHC who began IFN-α and ribavirin therapy during the recruitment period April 2001 to April 2003 were included in the study. Patients with a history of major depressive disorder were excluded. Results Of 113 co-infected patients who started IFN-α therapy during the recruitment period, 45 (40%) developed symptoms of depression (sadness, tiredness and apathy). Twenty of them (44%) were treated with citalopram, a selective serotonin re-uptake inhibitor, resulting in a significant improvement in their symptoms. Most of the patients (60%) showed depressive side effects in the first 3 months after initiation of IFN-α. In addition, during the study, three patients developed psychotic symptoms and one committed suicide. Conclusions The incidence of depressive symptoms in patients with HIV/HCV co-infection treated with IFN-α is high. Most of the depressive symptoms were not severe and improved with antidepressant therapy, without reduction or cessation of IFN-α therapy. During the first weeks after initiating IFN-α therapy for HIV/HCV co-infection, close assessment of psychiatric symptoms is recommended. Early treatment of these side effects with antidepressants would help avoid early dropouts from interferon therapy.
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Affiliation(s)
| | - Jordi Blanch
- Clinical Institute of Psychiatry and Psychology, Hospital Clínic Universitari de Barcelona, Barcelona, Spain
| | | | | | | | | | | | | | | | | | | | - Joan de Pablo
- Clinical Institute of Psychiatry and Psychology, Hospital Clínic Universitari de Barcelona, Barcelona, Spain
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Affiliation(s)
- Mark W Russo
- Division of Digestive Diseases, University of North Carolina at Chapel Hill, 27599, USA
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Portal I, Bourlière M, Halfon P, De Lédinghen V, Couzigou P, Bernard PH, Blanc F, Caroli-Bosc F, Arpurt JP, Vetter D, Mathieu-Chandelier C, Chazouillères O, Thiefin G, Pol S, Sogni P, Abergel A, Bailly F, Picon M, Debonne JM, Zamora C, Alleman I, Moreau X, Doll F, Eugène C, Ducloux S, Larrey D, Ouzan D, Grimaud JC, Gouvernet J, Botti G, Gérolami V, Khiri H, Gérolami A, Gauthier AP, Botta-Fridlund D. Retreatment with interferon and ribavirin vs interferon alone according to viraemia in interferon responder-relapser hepatitis C patients: a prospective multicentre randomized controlled study. J Viral Hepat 2003; 10:215-23. [PMID: 12753341 DOI: 10.1046/j.1365-2893.2003.00426.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Low pretreatment viral load has consistently been shown to be an independent predictor of sustained response (SR) in patients with chronic hepatitis C infection. We assessed the efficacy of interferon (IFN) plus ribavirin vs IFN alone in low viraemic patients (<2 millions copies/mL) who had relapsed to a previous course of IFN and the efficacy of 24 vs 48 week combination therapy in high viraemic patients. Two hundred and ninety-seven patients were randomly assigned to one of the four regimens after stratification on pretreatment viral load. All patients received IFN-alpha2b (6 million units thrice weekly for 24 weeks and 3 million units thrice weekly for 24 weeks). Patients with low viraemia received either IFN-alpha2b alone for 48 weeks (R1: 42 patients) or IFN-alpha2b plus ribavirin (600 mg/day) for 24 weeks and IFN-alpha2b alone for the next 24 weeks (R2: 48 patients). Patients with high viral load received either IFN-alpha2b plus ribavirin for 24 weeks and then IFN-alpha2b alone for the next 24 weeks (R3: 104 patients) or IFN-alpha2b plus ribavirin for 48 weeks (R4: 103 patients). In low viraemic patients the rate of SR was 37.7% in group R1 and 59.6% in group R2 (P < 0.05). In high viraemic patients, the rate of SR was 44.7% in group R3 and 51.4% in group R4 (P: NS). Thirty-one patients discontinued treatment (10.4%) without difference regarding treatment regimen. In the regimen using ribavirin we found no difference in terms of SR between patients receiving a dose of ribavirin below 10.6 mg/kg/day (55%) or over 10.6 mg/kg/day (58%). Histological improvement occurred in 70.2% of patients regardless of the regimen. Logistic regression showed that genotype 2 and 3, Knodell score <6 and alanine aminotransferase pretreatment level >3 x upper limit of normal were significantly and independently correlated with SR. In low viraemic patients who relapsed to a previous IFN treatment, combination therapy using high-dose IFN and low-dose ribavirin is better than high-dose IFN alone. In high viraemic patients there was no benefit in increasing the duration of combination therapy from 24 to 48 weeks. In this study, it was found that low dose of ribavirin can be used safely and there is no effect of ribavirin dose on SR.
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Affiliation(s)
- I Portal
- Department of Hepato-gastroenterology, Hospital La Conception, 13008 Marseille, France
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Abstract
Hepatitis C and HIV/AIDS are among the most significant infectious diseases of our time. Psychiatric patients are often part of the higher risk population to contract these diseases, and patients who have contracted these diseases experience a wide variety of psychiatric problems associated with the underlying infection and with its treatment. The authors provide an overview of these infectious diseases and then describe the varying roles psychiatrists have in caring for these patients in the various settings of their work. The complexity of these patients presents a unique challenge to, and opportunity for, psychiatrists to integrate and coordinate their interventions with those of other medical providers and thereby enhance the patient's cooperation with all aspects of care.
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Affiliation(s)
- Stephen Price
- Department of Psychiatry, Albany Medical College, Capital District Psychiatric Center, Albany, NY, USA.
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Clark CH, Mahoney JS, Clark DJ, Eriksen LR. Screening for depression in a hepatitis C population: the reliability and validity of the Center for Epidemiologic Studies Depression Scale (CES-D). J Adv Nurs 2002; 40:361-9. [PMID: 12383188 DOI: 10.1046/j.1365-2648.2002.02378.x] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
RATIONALE Depression is reported as a serious adverse event of antiviral therapy used to treat patients with hepatitis C (HCV); therefore, there is a need to identify a reliable and valid measure of depressive symptoms for this population. AIMS To determine reliability, construct validity and predictive validity of the Center for Epidemiological Studies Depression Scale (CES-D) in a hepatitis C (HCV) population. ETHICAL ISSUES Study reviewed/approved by the University Institutional Review Board and informed consent obtained. METHODS Longitudinal design testing psychometric properties of the CES-D prior to treatment and 4 and 24 weeks postinitiation of treatment. Reliability was tested using Cronbach's coefficient alpha. Construct validity was tested, prior to therapy, using principal components factoring with varimax rotation. Predictive validity was tested using repeated measures analysis of variance (anova) of CES-D scores at 4 and 24 weeks postinitiation of treatment. RESULTS Non-probability sample, 116 adult HCV patients [62 (53%) males and 54 (47%) females]. Reliability (Cronbach's alpha) = 0.88 pretreatment, 0.89 week 4 and 0.90 week 24. Construct validity testing revealed four factors: negative affect; positive affect; somatic; and depressed affect/somatic. Exception for two items, 'felt sad' and 'couldn't get going', all items loaded distinctly with correlation coefficients in the range of 0.51-0.84. Predictive validity testing revealed a statistically significant effect over time (P < 0.001) in the direction predicted (pretreatment x = 13.97; post 4 weeks x = 19.54 and 24 weeks x = 19.97). CONCLUSIONS The CES-D is a reliable and valid instrument to screen for depressive symptoms in HCV patients. The instrument detected the predicted increase in depression associated with HCV. Examination of the sensitivity and specificity is needed to determine the most accurate cut-off score.
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Affiliation(s)
- Cinda H Clark
- Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
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Abstract
Interferon and ribavirin combination therapy for chronic hepatitis C produces a number of well-described side effects that are dominated by fatigue, influenza-like symptoms, hematologic abnormalities, and neuropsychiatric symptoms. Combination therapy with pegylated interferons (peginterferon alfa-2a and alfa-2b) yields an adverse event profile similar to standard interferon, although the frequency of certain adverse events may vary by preparation. Premature withdrawal from therapy due to adverse events was required in 10% to 14% of participants in registration trials of these agents. Most adverse events were safely and effectively managed by dose reduction using predetermined criteria. The most common indications for dose reduction were hematologic abnormalities, such as anemia and neutropenia, with the latter more frequent in peginterferon treatment arms. Recent data suggest that maintaining adherence to a prescribed treatment regimen can enhance antiviral response. Strategies to maximize adherence are being developed and, in the future, may include early identification of and therapy for depression and the selective use of hematopoietic growth factors to ameliorate hematologic abnormalities.
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Affiliation(s)
- Michael W Fried
- Division of Digestive Diseases, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
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Abstract
Interferon and ribavirin combination therapy for chronic hepatitis C produces a number of well-described side effects that are dominated by fatigue, influenza-like symptoms, hematologic abnormalities, and neuropsychiatric symptoms. Combination therapy with pegylated interferons (peginterferon alfa-2a and alfa-2b) yields an adverse event profile similar to standard interferon, although the frequency of certain adverse events may vary by preparation. Premature withdrawal from therapy due to adverse events was required in 10% to 14% of participants in registration trials of these agents. Most adverse events were safely and effectively managed by dose reduction using predetermined criteria. The most common indications for dose reduction were hematologic abnormalities, such as anemia and neutropenia, with the latter more frequent in peginterferon treatment arms. Recent data suggest that maintaining adherence to a prescribed treatment regimen can enhance antiviral response. Strategies to maximize adherence are being developed and, in the future, may include early identification of and therapy for depression and the selective use of hematopoietic growth factors to ameliorate hematologic abnormalities.
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Affiliation(s)
- Michael W Fried
- Division of Digestive Diseases, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
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Nestler EJ, Gould E, Manji H, Buncan M, Duman RS, Greshenfeld HK, Hen R, Koester S, Lederhendler I, Meaney M, Robbins T, Winsky L, Zalcman S. Preclinical models: status of basic research in depression. Biol Psychiatry 2002; 52:503-28. [PMID: 12361666 DOI: 10.1016/s0006-3223(02)01405-1] [Citation(s) in RCA: 384] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Approximately one half-century ago several classes of medications, discovered by serendipity, were introduced for the treatment of depression and bipolar disorder. These highly effective medications revolutionized our approach to mood disorders and helped launch the modern era of psychiatry. Yet our progress since those serendipitous discoveries has been disappointing. We still do not understand with certainty how those medications produce their desired clinical effects. We have not introduced newer medications with fundamentally different mechanisms of action than the older agents. We have not identified the genetic and neurobiological mechanisms underlying depression and mania, nor do we understand the mechanisms by which nongenetic factors influence these disorders. We have only a rudimentary understanding of the circuits in the brain responsible for the normal regulation of mood and affect, and of those circuits that function abnormally in mood disorders. In approaching these gaps in our knowledge, this workgroup highlighted four major areas for future investment. These include developing better animal models of mood disorders; identifying genetic determinants of normal and abnormal mood in humans and animals; discovering novel targets and biomarkers of mood disorders and treatments; and increasing the recruitment of investigators from diverse backgrounds to mood disorders research.
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Affiliation(s)
- Eric J Nestler
- Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
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Fontana RJ, Schwartz SM, Gebremariam A, Lok ASF, Moyer CA. Emotional Distress During Interferon-α-2B and Ribavirin Treatment of Chronic Hepatitis C. PSYCHOSOMATICS 2002; 43:378-85. [PMID: 12297606 DOI: 10.1176/appi.psy.43.5.378] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The aim of the study was to describe the use of the Brief Symptom Inventory in characterizing the type and severity of emotional distress in 26 patients with chronic hepatitis C who were receiving interferon-alpha-2B and ribavirin. The 6-month actuarial incidence of neuropsychiatric toxicity, determined by physician interview, was 58%. Significant differences in mean depression, anxiety, and somatization Brief Symptom Inventory T scores were noted in the 15 patients with clinically apparent neuropsychiatric toxicity compared to the 11 patients without neuropsychiatric toxicity. Because of its brevity and simplicity, the Brief Symptom Inventory may prove to be a useful adjunct to clinician assessment in detecting and monitoring emotional distress during interferon-alpha treatment of chronic hepatitis C.
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Affiliation(s)
- Robert J Fontana
- Department of Internal Medicine and the Consortium for Health Outcomes Innovation and Cost-Effectiveness Studies, University of Michigan Medical School, Ann Arbor, MI 48109-0362, USA.
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Fontana RJ, Hussain KB, Schwartz SM, Moyer CA, Su GL, Lok ASF. Emotional distress in chronic hepatitis C patients not receiving antiviral therapy. J Hepatol 2002; 36:401-7. [PMID: 11867185 DOI: 10.1016/s0168-8278(01)00280-x] [Citation(s) in RCA: 88] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND/AIMS The aim of our study was to determine the prevalence, type, and severity of emotional distress in a large group of consecutive chronic hepatitis C (CHC) patients not receiving anti-viral therapy. METHODS The brief symptom inventory and a 67-item questionnaire with the SF-36 embedded within it were used to study 220 outpatients with compensated CHC. RESULTS Seventy-seven (35%) participants reported significantly elevated global severity index (GSI) T-scores compared to an expected frequency of 10% in population controls. In addition, significantly elevated depression, anxiety, somatization, psychoticism, and obsessive-compulsive subscale T-scores were reported in 28-40% of subjects. Subjects with an active psychiatric co-morbidity had significantly higher GSI and subscale T-scores compared to subjects with active medical co-morbidities and subjects without medical or psychiatric co-morbidities (P<0.01). However, patients with CHC alone also had a higher frequency of elevated GSI T-scores compared to population controls (20 versus 10%). GSI and subscale T-scores were strongly associated with SF-36 summary scores (P<0.001). CONCLUSIONS Clinically significant emotional distress was reported in 35% of CHC patients not receiving antiviral therapy. In addition to depression, a broad array of psychological symptoms were observed. Further investigation into the etiopathogenesis and treatment of emotional distress in CHC patients is warranted.
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Affiliation(s)
- Robert J Fontana
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, 3912 Taubman Center, Ann Arbor, MI 48109-0362, USA.
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Fontana RJ, Walsh J, Moyer CA, Lok ASF, Webster S, Klein S. High-dose interferon alfa-2b and ribavirin in patients previously treated with interferon: results of a prospective, randomized, controlled trial. J Clin Gastroenterol 2002; 34:177-82. [PMID: 11782615 DOI: 10.1097/00004836-200202000-00015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Kinetic studies have demonstrated a more rapid reduction in hepatitis C virus (HCV) RNA levels among patients taking high daily doses of interferon compared with those taking standard-dose interferon. GOALS To compare the efficacy and safety of high-dose interferon alfa-2b and ribavirin with standard-dose interferon alfa-2b and ribavirin in chronic hepatitis C patients previously treated with interferon. STUDY One hundred seven patients (30 interferon relapsers and 77 interferon nonresponders) were randomized to take either high-dose interferon alfa-2b in combination with ribavirin (group A) (consisting of 5 MU/d for 4 weeks, 5 MU three times weekly for 8 weeks, and then 3 MU three times weekly for 36 weeks) or standard-dose interferon alfa-2b and ribavirin (group B) for 48 weeks. Serum alanine transaminase (ALT), HCV RNA levels, and safety data were prospectively collected and compared during treatment and at week 24 of follow-up. RESULTS The mean serum ALT and HCV RNA levels, as well as the proportion of patients with genotype 1 and cirrhosis and who were African American, were similar in the two treatment groups at study entry. The rates of suppression of HCV RNA to undetectable levels at weeks 4, 12, and 48 were similar. In addition, the sustained virologic response rates at week 24 of follow-up were similar in groups A and B (29% vs. 39%, respectively, p = 0.277). Clinical variables that correlated with a sustained virologic response included a history of relapse to previous interferon therapy and non-1 HCV genotype ( p < 0.01). CONCLUSIONS Short-term, high-dose interferon alfa-2b and ribavirin failed to demonstrate a tangible benefit compared with standard-dose interferon alfa-2b and ribavirin. However, our study results and others suggest that standard-dose interferon and ribavirin for 48 weeks should be considered for selected patients who did not respond to previous interferon therapy.
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Affiliation(s)
- Robert J Fontana
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
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Affiliation(s)
- G L Davis
- University of Florida College of Medicine, Gainesville 32610-0214, USA
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