Hepatitis C, interferon alfa, and depression

Zdilar, Darko; Franco-Bronson, Kathleen; Buchler, Nancy M.; Locala, Joseph A.; Younossi, M.P.H. Zobair M.

doi:10.1053/jhep.2000.7880

Cited by 202 publications

(120 citation statements)

References 72 publications

(82 reference statements)

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“…The relationship of depression and interferon therapy has recently been reviewed. 42,43 Mechanisms of interferon-induced depression remain largely speculative. Interferon may induce proinflammatory cytokines (tumor necrosis factor, interleukin 1, interleukin 6) to promote "sickness behavior" and may also have effects on the hypothalamic-pituitary-adrenal axis.…”

Section: Management Of Specific Adverse Eventsmentioning

confidence: 99%

“…Interferon may induce proinflammatory cytokines (tumor necrosis factor, interleukin 1, interleukin 6) to promote "sickness behavior" and may also have effects on the hypothalamic-pituitary-adrenal axis. 42 Recent attention has also focused on the relationship of interferon to alterations in serotonin activity. Serum levels of tryptophan, a serotonin precursor, are reduced during interferon therapy.…”

Section: Management Of Specific Adverse Eventsmentioning

confidence: 99%

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Side effects of therapy of hepatitis C and their management

2002

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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. (HEPATOLOGY 2002;36: S237-S244.)T he side effect profile of combination therapy using standard interferon and ribavirin has been well described. [1][2][3][4] The major types of side effects include fatigue, influenza-like symptoms, gastrointestinal disturbances, neuropsychiatric symptoms, and hematologic abnormalities. 1,2 These side effects may be treatment limiting and require dose reduction or drug discontinuation. 3,4 Numerous other side effects occur with lower frequencies but may still have an impact on the tolerability of antiviral therapy. 2 Pegylated interferons (peginterferon alfa-2a and peginterferon alfa-2b) have significantly improved pharmacokinetics, 5-8 resulting in improved antiviral efficacy, which also has the potential to alter the side effect profile. This review will focus on the frequency and management of side effects reported with the use of peginterferon and ribavirin for the treatment of chronic hepatitis C based on data from 2 large registration trials that compared these agents with standard interferon and ribavirin combination therapy. Peginterferon Alfa-2a and RibavirinDiscontinuations and Dose Modification. The results of a large phase III clinical trial of peginterferon alfa-2a and ribavirin have been reported recently. 8 More than 1,100 subjects were randomized to therapy with peginterferon alfa-2a and ribavirin, peginterferon alfa-2a and placebo, or standard interferon alfa-2b and ribavirin. Premature withdrawal from therapy due to laboratory abnormalities or adverse events in the combination arms with either peginterferon (10%) or standard interferon (11%) was comparable 8 (Table 1). Interestingly, this rate of discontinuation for either combination arm was lower than previously reported in earlier trials using standard interferon and ribavirin (approximately 20%), 4,9 suggesting improv...

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Section: Management Of Specific Adverse Eventsmentioning

confidence: 99%

Section: Management Of Specific Adverse Eventsmentioning

confidence: 99%

Side effects of therapy of hepatitis C and their management

2002

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“…81 The mild-tomoderate depression that occurs with interferon therapy can be successfully managed with selective serotonin-reuptake inhibitors. [82][83][84][85] Nevertheless, severe psychiatric disease is a major impediment to therapy. 86 Unfortunately, hepatitis C is often associated with psychiatric disease and may be more common in patients with major psychiatric illnesses.…”

Section: Treatment Of Hepatitis C In Understudied Populationsmentioning

confidence: 99%

Understudied populations with hepatitis C

Strader

2002

Hepatology

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Managing patients with hepatitis C virus (HCV) infection consists primarily of antiviral treatment, currently with peginterferon and ribavirin. Unfortunately, treatment recommendations derive largely from trials that have focused on highly selected patient populations. As a consequence of the strict inclusion and exclusion criteria in these studies, more than half of all HCV-infected patients would be ineligible for enrollment. Even among the selected patients enrolled into studies, only 50% achieve a sustained virological response (SVR).Patients not eligible for current therapies include those with mild disease and normal alanine aminotransferase (ALT) levels, patients with advanced and decompensated liver disease, children, the elderly, patients with ongoing or recent alcohol and substance abuse, renal disease, human immunodeficiency virus ( H epatitis C is an important cause of acute and chronic liver disease worldwide and the most common indication for liver transplantation in adults in the United States. Since the discovery of the hepatitis C virus (HCV) in 1989 and its linkage to non-A, non-B hepatitis, there have been major advances in knowledge of the incidence and prevalence of this infection, its clinical manifestations, natural history, molecular virology, histopathology, and treatment. At present, the management of patients with hepatitis C focuses largely on combination antiviral treatment using a 24-or 48-week course of peginterferon and ribavirin. Two large trials evaluating the safety and efficacy of this combination therapy have demonstrated sustained virological responses (SVR) in slightly more than 50% of patients. 1,2 It is important to stress, however, that response rates of 50% in randomized, controlled trials of therapy do not guarantee that 50% of all patients with chronic hepatitis C can be or will be successfully treated. Patients enrolled in the registration trials of combination therapy were highly selected and not fully representative of the broader population of patients with chronic HCV infection. The strict inclusion and exclusion criteria used in registration trials often exclude populations that have high rates of hepatitis C. Furthermore, chronic hepatitis C is common in populations that are not reached by clinical trials of new and investigational therapies. Because patients enrolled in registration trials of new antiviral treatments are a selected group, the applicability of results of these trials to the general population is problematic.

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“…Uma delas é o fato de pacientes portadores de transtornos psiquiátricos apresentarem maior prevalência de infecção pelo HCV que a população geral. A outra é a maior prevalência de transtornos psiquiátricos em indivíduos infectados pelo HCV, sendo a depressão o distúrbio mais freqüente e clinicamente importante (Zdilar et al, 2000).…”

Section: Vírus Da Hepatite Cunclassified

“…Os motivos de tal variação foram os mesmos relatados previamente nos trabalhos com HIV, ressaltando-se os efeitos colaterais psiquiátricos da terapia antiviral à base de interferon (Zdilar et al, 2000;Wessely e Pariante, 2002).…”

Section: Vírus Da Hepatite Cunclassified

Infecções virais e depressão

Stumpf¹,

Rocha

Proietti

2006

J. bras. psiquiatr.

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ResumoObjetivo: A associação entre depressão e viroses é estudada há quase dois séculos, com resultados conflitantes. O objetivo deste trabalho é fazer uma análise crítica dos estudos existentes na literatura sobre essa relação. Métodos: A pesquisa bibliográfica utilizou as fontes eletrônicas de busca MEDLINE e LILACS (1966 a agosto 2005). As referências dos artigos foram utilizadas como fonte adicional de consulta. Resultados: Foram abordados os trabalhos que trataram da associação entre depressão e os vírus HIV, HCV, EBV, influenza, HSV, HBV, HAV, BDV e HTLV. A relação entre HIV e depressão mostrou-se bem documentada na literatura. Existem indícios de que a prevalência desse transtorno nos indivíduos infectados pelo HIV seja maior que a encontrada nos soronegativos. Além disso, estudos constataram que a depressão está associada a pior prognóstico da infecção. Quanto à associação entre HCV e depressão, os trabalhos sugeriram maior prevalência desse transtorno psiquiátrico nos portadores do HCV comparados à população geral. Não existem evidências científicas suficientes para dar suporte à relação entre os demais vírus e depressão. Conclusão: As associações mais bem fundamentadas foram aquelas entre depressão e os vírus HIV e HCV. A relação entre as demais viroses e depressão precisa ser mais bem estudada, e trabalhos com delineamento adequado se fazem necessários. Palavras-chave: depressão, viroses, HIV, HCV, HTLV. AbstractObjective: The association between depression and viruses has been evaluated for almost two centuries now, with conflicting results. The objective of the present study is to perform a critical review of published studies in the literature about this relationship. Methods: Databases MEDLINE and LILACS were searched between 1966 and 2005 (until August). The references of the articles were used as additional source of data. Results: Studies about the link between depression and infection with viruses HIV, HCV, EBV, influenza, HSV, HBV, HAV, BDV and HTLV were analyzed. The association between HIV and depression was well documented in literature. There are evidences that the prevalence of this disorder in HIV-infected individuals is greater than that found in seronegatives. Moreover, studies concluded that depression is associated with a worse course of infection. Regarding the link between HCV and depression, studies suggested a greater prevalence of this psychiatric disorder in HCV-infected people compared with general population. There is not enough scientific evidence to support the association between other viruses and depression. Conclusion: The best-studied relationships were those between depression and viruses HIV and HCV. Regarding the association of other viruses with depression, more research is needed.

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Hepatitis C, interferon alfa, and depression

Cited by 202 publications

References 72 publications

Side effects of therapy of hepatitis C and their management

Side effects of therapy of hepatitis C and their management

Understudied populations with hepatitis C

Infecções virais e depressão

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