Letter to the Editor Received: October 4, 2013 Accepted after revision: January 11, 2014 Published online: August 6, 2014
Psychother Psychosom 2014;83:308–309 DOI: 10.1159/000358527
Incidence of Depression in Patients with Chronic Hepatitis C Receiving Combination Therapy of Pegylated Interferon-Alpha and Ribavirin Sudhir Mahajana, Ajit Avasthia, Sandeep Grovera, Yogesh K. Chawlab Departments of a Psychiatry and b Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Sir, We read the article by Baranyi et al. [1], in which the authors comprehensively evaluated the biopsychosocial effects of interferon-α (IFN-α) treatment in patients with chronic hepatitis C. The authors reported that more than half (53.7%) of patients fulfilled the criteria of depression at least once during the treatment and they identified many important psychosocial factors which contribute to the development of depression. We also conducted a prospective study to evaluate the incidence of depression in patients with hepatitis C virus (HCV) infection receiving combination therapy of pegylated IFN-α and ribavirin. The study included patients found positive for HCV and prescribed combination of pegylated IFN-α 2a/2b plus ribavirin. Patients with concomitant hepatitis B virus infection, autoimmune disorders and chronic physical illness were excluded. Patients using alcohol/opioids on a regular basis and currently not abstinent (in the last 4 weeks) and those on any antidepressant or antipsychotic medication were excluded. Consenting patients were initially evaluated using the Mini International Neuropsychiatric Interview (MINI) for the presence of psychiatric illness (past and present) and those found positive for a lifetime psychiatric illness (except substance dependence) were
excluded. Those patients who were free from lifetime psychiatric illness were further assessed on the Patient Health Questionnaire-9 (PHQ-9). These subjects were serially followed at 2, 4, 8 and 12 weeks and were assessed on PHQ-9. Those found to have major depressive disorder (MDD) as per PHQ-9 at any time during the follow-up were assessed in detail by using MINI to confirm the diagnosis of depression. One hundred and nine consecutive patients diagnosed with HCV infection and recommended to receive pegylated IFN-α 2a/2b and ribavirin by their treating hepatologist were approached, of which 27 patients were excluded because of the presence of physical or psychiatric comorbidity. The final study sample comprised 82 patients. The mean age (±SD) of the study sample was 41.76 (±11.6) years. About two thirds of the participants were male (67.1%). The most common genotype of HCV infection in the study group was type 3 (70.7%). The mean (±SD) hepatitis C viral load at baseline was 1,638,700 ± 2,592,700 IU/ml. One half of the study sample (50%) received pegylated IFN-α 2a and the other half received pegylated IFN-α 2b. Table 1 shows the emergence of depressive symptoms and syndromal depression. At 2 weeks, 6 patients met the criteria for MDD as per PHQ-9, an additional 13 patients had other depressive disorder as per PHQ-9 but none of the patients was found to have a major depressive episode (MDE) as per MINI. At 4 weeks, about 10% fulfilled the criteria for other depressive disorder and one fourth (n = 19; 23.2% of the total sample) had MDD as per PHQ-9. When these 19 participants with MDD as per PHQ-9 were evaluated on MINI, 16 (19.5% of the total sample) fulfilled the criteria of MDE as per MINI. At week 8, 7 (10.6%) of the remaining 66 participants (i.e., those who were not found to have MDE at week 4 assessment) had other depressive disorder and 8 (12.1%) fulfilled the criteria of MDD as per PHQ-9. At 12 weeks, none of the remaining patients (n = 59) had MDD and 7 patients were found to have other depressive disorder as per PHQ-9. In total, 23 (28.05%) patients developed MDE as per MINI. Another 15 (18.3%) patients
Table 1. Evolution of depression during study period
MDD as per PHQ-9 Other depressive disorder as per PHQ-9 MDE as per MINI Symptoms resolved
Baseline (n = 82)
2 weeks (n = 82)
4 weeks (n = 82)
8 weeks (n = 66)
12 weeks (n = 59)
Total (n = 82)
0 0 0 0
6 (7.3%) 13 (15.8%) 0 0
19 (23.2%) 8 (9.8%) 16 (19.5%) 2 (2.4%)
8 (12.1%) 7 (10.6%) 7 (10.6%) 3 (4.5%)
0 7 (11.9%) 0 3 (5.1%)
24 (29.3%) 14 (17.1%) 23 (28.05%) 8 (9.8%)
MDD: if patients had at least 5 responses in the shaded section (score of 2 or more on first 8 items and 1 or more for the 9th item) with at least one of the first 2 items being scored as positive. Other depressive disorder: if patients had 2 – 4 responses in the shaded section (i.e., scored 2 or 3 on various items of PHQ-9).
© 2014 S. Karger AG, Basel 0033–3190/14/0835–0308$39.50/0 E-Mail [email protected] www.karger.com/pps
Dr. Sandeep Grover Department of Psychiatry Postgraduate Institute of Medical Education and Research Chandigarh 160012 (India) E-Mail drsandeepg2002 @ yahoo.com
met the criteria of MDD (n = 1) or other depressive disorder (n = 14) as per PHQ-9 during the study period. Of these 15 patients, in 8 patients other depressive disorders seen at a particular assessment disappeared in subsequent assessments. Further, most of the patients who developed MDD (as per PHQ-9) and MDE (as per MINI) did so by 4 weeks of therapy. In the present study, those who developed MDD had higher scores on PHQ-9 at the baseline assessment. During the study period, 25 (30.5%) participants developed anemia and 8.5% (n = 7) patients were found to have thyroid dysfunction at 12 weeks. None of the sociodemographic and clinical variables were found to be a risk factor for the development of MDE (as per MINI). With regard to the laboratory parameters, those who developed MDE had a higher prevalence of anemia (39 vs. 8.9%; χ2 value with Yates’ correction 5.81*), but there was no relationship between the development of MDE and prevalence of thyroid dysfunction at the last assessment. There was no significant difference between those who developed MDE and those who did not develop MDE with respect to HCV-RNA viral load at baseline, 4 weeks and 12 weeks. There was no significant difference in the incidence of depression in patients receiving either IFN-α 2a or 2b. Further, there was no difference in the dose of IFN of either type or the dose of ribavirin received by those who developed depression and those who did not develop depression. The incidence figure for MDE observed in our study is very similar to that reported in the meta-analysis which reported an incidence rate of 25% during the first 24 weeks and 28% by 48 weeks [2]. The time for development of depression seen in the present study is supported by the existing literature, including a meta-analysis, wherein peak incidence occurred between 4 and 12 weeks of therapy with interferon [2]. In our study, those who developed MDD had higher scores on PHQ-9 at the baseline assessment. This finding is in agreement with some of the earlier literature, which suggests that baseline depressive symptoms predict future depression [3–5]. To conclude, our study found that 28% of HCV patients developed an MDE within 12 weeks while receiving treatment with a combination of pegylated IFN-α and ribavirin, and another 18.3%
patients developed depressive symptoms not amounting to MDE as per the MINI. The majority of patients met the criteria for depression at 4–8 weeks of treatment. None of the sociodemographic variables studied predict depression. The development of depression is not associated with different types of interferon, the dose of interferon and viral clearance. Taking this into account, routine screening for depression is warranted using structured clinical interview or validated rating scales in patients with hepatitis C prior to the start of interferon treatment and periodically later. Those who have subthreshold depressive symptoms prior to the start of treatment should be considered at risk for depression and must be followed closely. Whenever a patient is found to have depression, depending on severity, surveillance should be increased and appropriate measures must be taken for the treatment of depression.
Incidence of Depression in Patients with Chronic Hepatitis C
Psychother Psychosom 2014;83:308–309 DOI: 10.1159/000358527
Disclosure Statement None. References 1 Baranyi A, Meinitzer A, Stepan A, Putz-Bankuti C, Breitenecker RJ, Stauber R, Kapfhammer HP, Rothenhäusler HB: A biopsychosocial model of interferon-alpha-induced depression in patients with chronic hepatitis C infection. Psychother Psychosom 2013;82:332–340. 2 Udina M, Castellví P, Moreno-España J, Navinés R, Valdés M, Forns X, Langohr K, Solà R, Vieta E, Martín-Santos R: Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. J Clin Psychiatry 2012;73:1128–1138. 3 Hauser P, Khosla J, Aurora H, Laurin J, Kling MA, Hill J, Gulati M, Thornton AJ, Schultz RL, Valentine AD, Meyers CA, Howell CD: A prospective study of the incidence and open-label treatment of interferoninduced major depressive disorder in patients with hepatitis C. Mol Psychiatry 2002;7:942–947. 4 Lotrich FE, Rabinovitz M, Gironda P, Pollock BG: Depression following pegylated interferon-alpha: characteristics and vulnerability. J Psychosom Res 2007;63:131–135. 5 Castellvi P, Navinés R, Gutierrez F, Jiménez D, Márquez C, Subirà S, Solà R, Martín-Santos R: Pegylated interferon and ribavirin-induced depression in chronic hepatitis C: role of personality. J Clin Psychiatry 2009;70: 817–828.
309
Copyright: S. Karger AG, Basel 2014. Reproduced with the permission of S. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.
Psychother Psychosom 2014;83:308–309 DOI: 10.1159/000358527
Incidence of Depression in Patients with Chronic Hepatitis C Receiving Combination Therapy of Pegylated Interferon-Alpha and Ribavirin Sudhir Mahajana, Ajit Avasthia, Sandeep Grovera, Yogesh K. Chawlab Departments of a Psychiatry and b Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Sir, We read the article by Baranyi et al. [1], in which the authors comprehensively evaluated the biopsychosocial effects of interferon-α (IFN-α) treatment in patients with chronic hepatitis C. The authors reported that more than half (53.7%) of patients fulfilled the criteria of depression at least once during the treatment and they identified many important psychosocial factors which contribute to the development of depression. We also conducted a prospective study to evaluate the incidence of depression in patients with hepatitis C virus (HCV) infection receiving combination therapy of pegylated IFN-α and ribavirin. The study included patients found positive for HCV and prescribed combination of pegylated IFN-α 2a/2b plus ribavirin. Patients with concomitant hepatitis B virus infection, autoimmune disorders and chronic physical illness were excluded. Patients using alcohol/opioids on a regular basis and currently not abstinent (in the last 4 weeks) and those on any antidepressant or antipsychotic medication were excluded. Consenting patients were initially evaluated using the Mini International Neuropsychiatric Interview (MINI) for the presence of psychiatric illness (past and present) and those found positive for a lifetime psychiatric illness (except substance dependence) were
excluded. Those patients who were free from lifetime psychiatric illness were further assessed on the Patient Health Questionnaire-9 (PHQ-9). These subjects were serially followed at 2, 4, 8 and 12 weeks and were assessed on PHQ-9. Those found to have major depressive disorder (MDD) as per PHQ-9 at any time during the follow-up were assessed in detail by using MINI to confirm the diagnosis of depression. One hundred and nine consecutive patients diagnosed with HCV infection and recommended to receive pegylated IFN-α 2a/2b and ribavirin by their treating hepatologist were approached, of which 27 patients were excluded because of the presence of physical or psychiatric comorbidity. The final study sample comprised 82 patients. The mean age (±SD) of the study sample was 41.76 (±11.6) years. About two thirds of the participants were male (67.1%). The most common genotype of HCV infection in the study group was type 3 (70.7%). The mean (±SD) hepatitis C viral load at baseline was 1,638,700 ± 2,592,700 IU/ml. One half of the study sample (50%) received pegylated IFN-α 2a and the other half received pegylated IFN-α 2b. Table 1 shows the emergence of depressive symptoms and syndromal depression. At 2 weeks, 6 patients met the criteria for MDD as per PHQ-9, an additional 13 patients had other depressive disorder as per PHQ-9 but none of the patients was found to have a major depressive episode (MDE) as per MINI. At 4 weeks, about 10% fulfilled the criteria for other depressive disorder and one fourth (n = 19; 23.2% of the total sample) had MDD as per PHQ-9. When these 19 participants with MDD as per PHQ-9 were evaluated on MINI, 16 (19.5% of the total sample) fulfilled the criteria of MDE as per MINI. At week 8, 7 (10.6%) of the remaining 66 participants (i.e., those who were not found to have MDE at week 4 assessment) had other depressive disorder and 8 (12.1%) fulfilled the criteria of MDD as per PHQ-9. At 12 weeks, none of the remaining patients (n = 59) had MDD and 7 patients were found to have other depressive disorder as per PHQ-9. In total, 23 (28.05%) patients developed MDE as per MINI. Another 15 (18.3%) patients
Table 1. Evolution of depression during study period
MDD as per PHQ-9 Other depressive disorder as per PHQ-9 MDE as per MINI Symptoms resolved
Baseline (n = 82)
2 weeks (n = 82)
4 weeks (n = 82)
8 weeks (n = 66)
12 weeks (n = 59)
Total (n = 82)
0 0 0 0
6 (7.3%) 13 (15.8%) 0 0
19 (23.2%) 8 (9.8%) 16 (19.5%) 2 (2.4%)
8 (12.1%) 7 (10.6%) 7 (10.6%) 3 (4.5%)
0 7 (11.9%) 0 3 (5.1%)
24 (29.3%) 14 (17.1%) 23 (28.05%) 8 (9.8%)
MDD: if patients had at least 5 responses in the shaded section (score of 2 or more on first 8 items and 1 or more for the 9th item) with at least one of the first 2 items being scored as positive. Other depressive disorder: if patients had 2 – 4 responses in the shaded section (i.e., scored 2 or 3 on various items of PHQ-9).
© 2014 S. Karger AG, Basel 0033–3190/14/0835–0308$39.50/0 E-Mail [email protected] www.karger.com/pps
Dr. Sandeep Grover Department of Psychiatry Postgraduate Institute of Medical Education and Research Chandigarh 160012 (India) E-Mail drsandeepg2002 @ yahoo.com
met the criteria of MDD (n = 1) or other depressive disorder (n = 14) as per PHQ-9 during the study period. Of these 15 patients, in 8 patients other depressive disorders seen at a particular assessment disappeared in subsequent assessments. Further, most of the patients who developed MDD (as per PHQ-9) and MDE (as per MINI) did so by 4 weeks of therapy. In the present study, those who developed MDD had higher scores on PHQ-9 at the baseline assessment. During the study period, 25 (30.5%) participants developed anemia and 8.5% (n = 7) patients were found to have thyroid dysfunction at 12 weeks. None of the sociodemographic and clinical variables were found to be a risk factor for the development of MDE (as per MINI). With regard to the laboratory parameters, those who developed MDE had a higher prevalence of anemia (39 vs. 8.9%; χ2 value with Yates’ correction 5.81*), but there was no relationship between the development of MDE and prevalence of thyroid dysfunction at the last assessment. There was no significant difference between those who developed MDE and those who did not develop MDE with respect to HCV-RNA viral load at baseline, 4 weeks and 12 weeks. There was no significant difference in the incidence of depression in patients receiving either IFN-α 2a or 2b. Further, there was no difference in the dose of IFN of either type or the dose of ribavirin received by those who developed depression and those who did not develop depression. The incidence figure for MDE observed in our study is very similar to that reported in the meta-analysis which reported an incidence rate of 25% during the first 24 weeks and 28% by 48 weeks [2]. The time for development of depression seen in the present study is supported by the existing literature, including a meta-analysis, wherein peak incidence occurred between 4 and 12 weeks of therapy with interferon [2]. In our study, those who developed MDD had higher scores on PHQ-9 at the baseline assessment. This finding is in agreement with some of the earlier literature, which suggests that baseline depressive symptoms predict future depression [3–5]. To conclude, our study found that 28% of HCV patients developed an MDE within 12 weeks while receiving treatment with a combination of pegylated IFN-α and ribavirin, and another 18.3%
patients developed depressive symptoms not amounting to MDE as per the MINI. The majority of patients met the criteria for depression at 4–8 weeks of treatment. None of the sociodemographic variables studied predict depression. The development of depression is not associated with different types of interferon, the dose of interferon and viral clearance. Taking this into account, routine screening for depression is warranted using structured clinical interview or validated rating scales in patients with hepatitis C prior to the start of interferon treatment and periodically later. Those who have subthreshold depressive symptoms prior to the start of treatment should be considered at risk for depression and must be followed closely. Whenever a patient is found to have depression, depending on severity, surveillance should be increased and appropriate measures must be taken for the treatment of depression.
Incidence of Depression in Patients with Chronic Hepatitis C
Psychother Psychosom 2014;83:308–309 DOI: 10.1159/000358527
Disclosure Statement None. References 1 Baranyi A, Meinitzer A, Stepan A, Putz-Bankuti C, Breitenecker RJ, Stauber R, Kapfhammer HP, Rothenhäusler HB: A biopsychosocial model of interferon-alpha-induced depression in patients with chronic hepatitis C infection. Psychother Psychosom 2013;82:332–340. 2 Udina M, Castellví P, Moreno-España J, Navinés R, Valdés M, Forns X, Langohr K, Solà R, Vieta E, Martín-Santos R: Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. J Clin Psychiatry 2012;73:1128–1138. 3 Hauser P, Khosla J, Aurora H, Laurin J, Kling MA, Hill J, Gulati M, Thornton AJ, Schultz RL, Valentine AD, Meyers CA, Howell CD: A prospective study of the incidence and open-label treatment of interferoninduced major depressive disorder in patients with hepatitis C. Mol Psychiatry 2002;7:942–947. 4 Lotrich FE, Rabinovitz M, Gironda P, Pollock BG: Depression following pegylated interferon-alpha: characteristics and vulnerability. J Psychosom Res 2007;63:131–135. 5 Castellvi P, Navinés R, Gutierrez F, Jiménez D, Márquez C, Subirà S, Solà R, Martín-Santos R: Pegylated interferon and ribavirin-induced depression in chronic hepatitis C: role of personality. J Clin Psychiatry 2009;70: 817–828.
309
Copyright: S. Karger AG, Basel 2014. Reproduced with the permission of S. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.
