Interferon-Alpha Treatment in Patients with Chronic Viral Hepatitis C: The Incidence of Major Depression and Changes in Quality of Life

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1 130 Original Article / Özgün Makale Interferon-Alpha Treatment in Patients with Chronic Viral Hepatitis C: The Incidence of Major Depression and Changes in Quality of Life Kronik Hepatit C li Hastalarda nterferon-alfa Tedavisi: Majör Depresyonun nsidans ve Yaflam Kalitesinde De ifliklikler Mine fiah NGÖZ, Faruk U UZ, brahim ERAYMAN*, Nazmiye KAYA, Emel TÜRK ARIBAfi* Selçuk Üniversitesi Meram T p Fakültesi, Psikiyatri ve * nfeksiyon Hastal klar Anabilim Dal, Konya, Turkey ABSTRACT Objective: There are three aims of this study:- 1) to examine the incidence of interferon alpha (IFN-α) induced major depression, 2) to examine the associations between IFN-α induced major depression and clinical and sociodemographic characteristics and 3) to examine the impact of IFN-α on the quality of life in patients with chronic hepatitis C virus infection. Method: Thirty-six patients with chronic hepatitis C virus infection were evaluated by using the Structured Clinical Interview for DSM-IV, the Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS) and the World Health Organization Quality of Life Scale-Brief () before the treatment and 8 weeks after interferon alpha treatment. Results: Major depression developed in 10 (27.8%) of 36 patients during treatment with IFN-α. During the IFN-α treatment, HDRS and HARS scores significantly increased, and subscale scores of physical health, psychological health and environment significantly decreased. It was found that HDRS scores significantly increased in patients receiving IFN-α even if major depression did not develop at 8 weeks after the treatment. IFN-α induced major depression was associated with higher basal scores of HDRS and HARS, and lower basal scores of. Conclusion: IFN-α treatment is associated with an increased risk for major depression and it has a negative effect on the quality of life in patients with chronic hepatitis C virus infection. The mental status of all patients were evaluated before and after the IFN-α treatment. (Archives of Neuropsychiatry 2008; 45: 130-4) Key words: Interferon-alpha, major depression, hepatitis C, quality of life ÖZET Girifl: Bu çal flman n ilgili üç amac vard r: 1) Kronik hepatit C virus infeksiyonlu hastalarda interferon alfa tedavisine ba l majör depresyon insidans n araflt rmak 2) nterferon alfa (IFN-α) tedavisine ba l majör depresyonla sosyodemografik ve klinik özellikleri aras ndaki iliflkiyi araflt rmak 3) Kronik hepatit C virus infeksiyonlu hastalarda IFN-α tedavisinin yaflam kalitesine olan etkilerini araflt rmakt r. Yöntem: Kronik hepatit C virus infeksiyonlu 36 hasta interferon alfa tedavisinden önce ve tedaviden 8 hafta sonra DSM-IV çin Yap land r lm fl Klinik Görüflme, Hamilton Depresyon Derecelendirme Ölçe i HDÖ), Hamilton Anksiyete Derecelendirme Ölçe i (HAÖ) ve Dünya Sa l k Örgütü Yaflam Kalitesi Ölçe i K sa Formu () ile de erlendirildi. Bulgular: IFN-α tedavisi s ras nda 10 (%27.8) hastada majör depresyon geliflti. IFN-α tedavisi süresince, HDÖ ve HAÖ puanlar anlaml ölçüde artt ve in fiziksel sa l k, psikolojik sa l k ve çevre alanlar puanlar anlaml ölçüde azald. IFN-α tedavisi alan hastalarda tedaviden 8 hafta sonra majör depresyon geliflmese bile HDÖ puanlar n n anlaml ölçüde artt bulundu. IFN-α ya ba l majör depresyon, tedavi öncesi daha yüksek HDÖ ve HAÖ ve daha düflük puanlar ile iliflkiliydi. Sonuç: Kronik hepatit C virus infeksiyonlu hastalarda IFN-α tedavisi majör depresyon riskindeki art flla iliflkilidir ve bu hastalar n yaflam kalitesi üzerinde olumsuz etkiye sahiptir. Bütün hastalar n ruhsal durumu IFN-α tedavisinden önce ve sonra de erlendirilmelidir. () Anahtar kelimeler: nterferon-alfa, majör depresyon, hepatit C, yaflam kalitesi Introduction Hepatitis C virus infection (HCV) is an important cause of chronic liver disease (1). Interferon-alpha (IFN-α) is frequently used in the treatment of several diseases such as viral chronic hepatitis, some cancers and skin disorders and multiple sclerosis (2-5). In spite of its therapeutic effects, IFN-α commonly has various psychiatric side effects such as anxiety, depression, psychosis, mania and suicidal ideas or attempt. In addition, somatic symptoms such as fatigue, fever, headache, myalgia and arthralgia frequently occur during the treatment (6-8). Several studies reported that depressive symptoms have negative effects on the course of medical conditions, patients compliance to medical treatments and satisfaction wih treatments (9-11). Similarly, depressive symptoms occuring during IFN-α treatment may restrict the utility of the treatment, Address for Correspondence/Yaz flma Adresi: Dr. Mine fiahingöz, Selçuk Üniversitesi Meram T p Fakültesi, Psikiyatri Anabilim Dal, Konya, Turkey E-posta: drpekalkan@hotmail.com Received/Gelifl tarihi: Accepted/Kabul tarihi: Nöropsikiyatri Arflivi Dergisi, Galenos Yay nc l k taraf ndan bas lm flt r. Her hakk sakl d r. / Archives of Neuropsychiatry, Published by Galenos Publishing. All rights reserved.

2 Archives of Neuropsychiatry 2008; 45: Major Depression and Changes in Quality of Life 131 leading to early discontinuation or a decrease in the dose of IFN-α treatment (8,12). In addition, previous studies showed that depression occurs in 23-45% of the patients with chronic HCV during IFN-α therapy and may lead to suicidal attempts (12,13). IFN-α induced depression may be successfully treated by antidepressant medications (14-16). To identify patients at risk for depression is important, because IFN-α induced depression is a relatively common and serious clinical issue. There are several studies reporting association with age, female gender, history of psychiatric disorder, basal immune activation and anxiety and depression scores before IFN-α induced depression (17-20). The studies suggested that IFN-α therapy negatively influences the quality of life in patients with chronic HCV similarly to some other medical conditions (21-24). To date, many of these studies examining the relationship between depression and IFN-α treatment have been cross-sectionally designed or based on the depressive symptom rating scale. In this respect, prospective studies based on a structured clinical interview are relatively inadequate, particularly in developing countries. Moreover, compared to the prevalence of IFN-α induced depression, there is less data regarding factors associated with the depression. Finally, to the best of our knowledge, there is no prospective study about effects of IFN-α treatment on quality of life in patients with chronic HCV in our country, Turkey. In this study, we aimed to examine the incidence of major depression due to IFN-α therapy, and sociodemogarphic and clinical factors associated with IFN-α induced major depression, and the impact of IFN-α on quality of life in patients with chronic HCV. Method The study included 45 consecutive outpatients newly diagnosed with chronic HCV who were admitted to the Department of Infectious Diseases, Meram Faculty of Medicine, Selçuk University. Exclusion criteria were severe liver deficiency, severe additional medical illnesses (e.g., uncontrolled endocrine abnormalities, cardiovascular and pulmonary diseases, or medical conditions causing physical deficiency), history of a neurological disorder, psychotropic treatment within the previous 4 weeks. The goals and methods of this study were explained to all participants, and informed consent forms were obtained from them. Chronic HCV was diagnosed with serological tests (positive HCV RNA), abnormal liver tests and pathology of liver biopsy consistent with HCV. All the patients were treated with pegylated IFN-α2b. Before the start of IFN-α therapy, all patients were evaluated with the Structured Clinical Interview for DSM-IV (SCID-I) (25,26) with regard to major depression. The clinical interviews were made by the same psychiatrists. Four patients with major depression according to SCID-I during this evaluation were excluded from the study. In the other forty-one patients, the levels of depression, anxiety and quality of life were assessed with the Hamilton Depression Rating Scale (HDRS) (27,28), the Hamilton Anxiety Rating Scale (HARS) (29,30) and the World Health Organization Quality of Life Assessment Brief () (31,32), respectively. After 8 weeks of treatment, patients were reevaluated using the same clinical interview instruments. Three patients were excluded from the study because the IFN-α treatment was discontinued due to its physical side effects. Two patients refused the second interview after 8 weeks. Thereby, this study was completed by thirty-six patients. All statistical analyses were carried out using the Statistical Package for the Social Sciences (SPSS), version 13.0 for Windows (SPSS, Chicago, IL). The HDRS, HARS and WHOQOL- BREF scores before and after the IFN-α treatment were compared using the t test for dependent groups. Pearson correlation test was used to assess the relationships between and HDRS and HARS scores after 8 weeks of the therapy. To determine associations between IFN-α induced major depression and sociodemographic and clinical factors prior to the treatment, we used Fisher s exact test for categorical variables and t test for independent groups in continuous variables. All statistical significance levels were accepted as P< Results Of the 36 patients who completed the study, twenty (55.4%) were men and 16 (44.4%) were women with a mean age of 48.4±8.1 years. Thirty-four (94.4%) patients were married, 24 (66.7%) were unemployed, and 32 (94.4%) were primary school graduates. Ten patients had major depression at 8 weeks after the IFN-α therapy. In other words, the incidence rate of IFN-α induced major depression was 27.8%. Of these subjects, 6 (60%) were men, 4 (40%) were women and the mean age was 50.4±8.6 years. While the mean of total HDRS and HARS scores of the final sample (n=36) were 4.55±3.58 and 5.50±3.73 at the baseline, they were 8.83±9.16 and 10.16±11.4 at 8 weeks after therapy, respectively. The differences were statistically significant (p=0.000 for HDRS and p=0.001 for HARS) (Table 1). Domains of physical health, psychological health, environment but no social relationships of scores significantly decreased from the baseline at 8 weeks after the therapy (Table 1). When we compared the scale scores at baseline and after IFN-α in patients who did not develop major depression (n=26), a significant increase in the score of HDRS, and a significant decrease in physical health, psychological health, and environment subscale scores of were found. The scores of HARS and social relationships subscale scores of did not exhibit a significant change from the baseline at 8 weeks after IFN-α (Table 2). Pearson correlation analysis indicated that there was a significant negative correlation between the scores of HDRS, HARS and all domains of at 8 weeks after the treatment (Table 3).

3 132 Major Depression and Changes in Quality of Life Archives of Neuropsychiatry 2008; 45: We found no association between IFN-α induced major depression and sociodemographic characteristics. The basal scores of HDRS and HARS were significantly higher and all subscale scores of prior to the IFN-α were significantly lower in depressed patients compared to nondepressed ones at end of the study (Table 4). Discussion The present study shows that the incidence of major depression is 27.8% in patients with chronic hepatitis C receiving IFN-α treatment. The data about the incidence of IFN-α induced depression in patients with HCV are mostly derived from European countries and USA. Similar to our study in Turkey, many studies reported that the incidence rates of IFN-α induced major depression are 17-40% in European samples (17,19,20,33-35) and American samples (14,36). In addition, our incidence rate of major depression (23-44%) is consistent with results of studies conducted in Japan, which is an Asian country (18,37). In our country, the prevalence of depression in patients with chronic HCV treated with IFN-α was found to be 40% cross-sectioanally (38). In this topic, to the best of our knowledge, there are no prospective studies based on a structural psychiatric interview in Turkey. Our results suggest that the risk of IFN-α induced major depression in patients with chronic HCV is similar in Turkey to other countries. In the current study, depressive symptoms increased even if major depression did not develop in patients receiving IFN-α suggests and depressive symptoms due to IFN-α treatment were not only associated with the occurrence of major depression, but also the psychological status of clinically nondepressed patients is negatively affected. There are few studies exploring the risk factors for IFN-α induced depression. Previous studies suggested that higher baseline depression and anxiety scores predict IFN-α-induced depression (14,20), which is consistent with our results. Whereas some studies found that past history of a psychiatric disorder, advanced age, female gender is associated with IFN-α-induced depression (18,39), some studies reported no association between these factors and the occurrence of depression (17,40,41). In this study, there was no correlation between age, gender, marital status, education levels, employment status and IFN-α-induced depression. However, in our sample,a lower quality of life before IFN-α treatment was Table 1. HDRS, HARS and scores at baseline and at 8 weeks after IFN-α treatment in all patients with chronic HCV (n=36) At baseline At 8 weeks T P HDRS 4.55± ± HARS 5.50± ± Physical health 65.05± ± Psychological health 65.33± ± Social relationships 64.55± ± Environment 65.61± ± Table 2. HDRS, HARS and scores at baseline and at 8 weeks in patients who not developed depression after IFN-α treatment (n=26) At baseline At 8 weeks T P HDRS 2.76± ± HARS 3.61± ± Physical health 73.69± ± Psychological health 73.07± ± Social relationships 72.00± ± Environment 69.15± ± Table 3. Correlations between mean HDRS, HARS and scores after IFN-α treatment in all patients with chronic HCV (n=36) HDRS HARS r P r P Physical health Psychological health Social relationships Environment

4 Archives of Neuropsychiatry 2008; 45: Major Depression and Changes in Quality of Life 133 related to IFN-α-induced depression. To the best of our knowledge, there is no study assessing the association between the quality of life before treatment and IFN-α-induced depression in patients with chronic HCV. In the present study, it was found that domains of physical health, psychological health and environment, but not social relationships of quality of life, are negatively affected by IFN-α therapy in patients with chronic HCV. These findings are similar to previous prospective studies. Trask et al (21). Reported that the scores of domains of physical and psychological health of quality of life significantly decreased from baseline at 8 weeks after the treatment in patients with high risk melanoma receiving adjuvant interferon. Recently, a study conducted by Dan et al. (24) showed that quality of life in patients with HCV significantly reduced during IFN-α treatment. Results of this study also suggest that quality of life is affected negatively even if major depression did not develop in patients administered IFN-α. However, in this study, a negative correlation between quality of life levels and anxiety and depression scores after the treatment suggests that anxiety and depressive symptoms may play a role in reduction of quality of life in patients receiving IFN-α treatment. In addition to anxiety and depressive symptoms, somatic symptoms such as fever, headache, weakness, myalgia and arthralgia due to IFN-α treatment may be related to decline in quality of life levels. The present study has some limitations. First, this study has a relatively small sample size. Second, the absence of control subjects including HCV patients who did not receive the IFN-α Table 4. Sociodemographic characteristics and basal HDRS, HARS, and scores in patients who developed and not developed major depression after IFN-α treatment Patients with Patients without depression (n=10) depression (n=26) P Age (mean±sd) 50.40± ± Gender Female 4 (%40) 12 (%46.2) Male 6 (%60) 14 (%53.8) Marital status Married 8 (%80) 26 (%100) Divorced 2 (%20) 0 (%0) Educational level Primary 8 (%80) 26 (%100) University 2 (%20) 0 (%0) Working status Employed 4 (%40) 8 (%30.8) Unemployed 6 (%60) 18 (%69.2) HDRS 9.20± ± HARS 10.40± ± Physical health 42.60± ± Psychological health 45.20± ± Social relationships 45.20± ± Environment 56.40± ± treatment during the study period is a limitation. Third, in our study, the patients were assessed at baseline and 8 weeks after IFN-α treatment. The study does not indicate higher and lower risk periods in terms of development of major depression during IFN-α administration. Fourth, our study follow-up period is relatively short. 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