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Indian Journal of Pharmacology, Vol. 43, No. 2, March-April, 2011, pp. 210-211 Drug Watch IFN-α-2a (Interferon) and ribavirin induced suicidal attempt in a patient of chronic HCV: A rare case report Deep Inder1, HS Rehan1, Madhur Yadav2, Seema Manak1, Pawan Kumar3 1 Department of Pharmacology, Lady Hardinge Medical College and Associated, Hospitals, New Delhi - 110 001, India Correspondence Address: Deep Inder, Department of Pharmacology, Lady Hardinge Medical College and Associated, Hospitals, New Delhi - 110 001, India, drdeep73@yahoo.co.in Date of Submission: 13-Aug-2010 Code Number: ph11055 DOI: 10.4103/0253-7613.77375 Abstract Interferons (IFNs) are proteins produced by cells, fibroblasts and macrophages, in response to viral invasion, and mediates immune response. IFN-α and ribavirin are the approved treatment for HCV infection, but also carries a risk of neuropsychiatric adverse effects, viz. insomnia, irritability, mood changes, and depression. We present a case report of depression induced by IFN-α and ribavirin, leading to attempted suicide. Following the episode, antidepressant paroxetine (20 mg o.d.) and zolpidem (10 mg h.s) were added with psychotherapy. No significant improvement was observed. Patient was given a drug dechallenge (IFN-α and ribavirin). Dramatic improvement was seen over 1 month. Following rechallenge with combination, patient again experienced depressive symptoms with suicidal ideation. IFN-α and ribavirin were promptly stopped. Naranjo causality assessment scale revealed probable association with IFN-α and ribavirin. The report intends to improve awareness among clinicians to facilitate early diagnosis and intervention of similar cases.Keywords: Adverse effects, depression, IFN-α, ribavirin Introduction Hepatitis C is a major health problem globally with a prevalence of 3%. The only treatment till date is combination therapy, with interferon (IFN)-α and ribavirin. Besides clearance of HCV-RNA in patients on this combination therapy, numerous adverse effects are also associated. The predominant adverse effect is suicide. [1] We came across one case of major depression in a patient of chronic hepatitis C, with suicidal attempt, who was rescued, while on treatment with IFN-α and ribavirin. Case Report A 43-year-old man diagnosed with chronic hepatitis C viral infection was referred to medicine outdoor. His viral load was found to be 9.6 million copies/ml with genotype 1. He was started on therapy with IFN-α-2a (3 MIU thrice a week s.c) and ribavirin (1000 mg p.o/ day). The patient had no history of any intravenous drug intake. He had neither received any blood transfusion, nor had any history of multiple sex partners. Patient was admitted to surgery for operating appendectomy. During preoperative laboratory investigations, patient was reported to be positive for HCV, with raised levels of alanine transaminase and s. bilirubin. Liver biopsy revealed hepatic parenchymal destruction with lymphocytic infiltration of periportal regions with evident fibrosis. Screening tests for HBV, HAV, and HIV were negative. In initial 3 months of start of therapy with IFN-α-2a and ribavirin, patient experienced adverse effects in the form of high-grade fever, malaise, myalgia, and fatigue which were relieved by paracetamol (500 mg). After 16 weeks of therapy, patient reported to experience feeling of guilt, anxiety, fear, and sadness. Patient wanted to keep himself isolated from family and friends. He started blaming himself for financial crises he was facing that time. He was unable to perform his job as school teacher. Hamilton Depression Rating Scale (HDRS-17) revealed the patient to be suffering from moderate to severe depression with score of 15. [2] He was given psychotherapy for the same. Paroxetine (20 mg o.d.) and zolpidem (10 mg h.s.) were started along with IFN-α-2a and ribavirin. Patient did not respond significantly to antidepressants over 3 weeks. After 25 days of starting antidepressants, patient attempted suicide but was rescued in time. IFN-α-2a and ribavirin were withheld for 1 month and antidepressants were continued. Patient′s condition normalized and he started taking interest in self and surroundings. He started following his normal routine. Patient was advised to again continue IFN-α-2a and ribavirin, as patient was otherwise responding to the treatment. There was clearance of HCV-RNA in patient, which was performed after suicidal attempt. But unfortunately, patient again experienced same symptoms of depression and ideas of self destruction within 3 weeks of start of therapy. IFN-α-2a and ribavirin were promptly stopped. Patient showed dramatic improvement within 1 week. His mood was normalized and he started taking interest in his normal routine. Discussion The morbidity and mortality associated with HCV can be significant. For patients of HCV, IFN-α alone or in combination with ribavirin are the approved treatments. But unfortunately, this limited therapy has its own adverse effects which can prove fatal if patient is not monitored. [3] There are very few case reports of suicidal attempts and completed suicides associated with IFN-α and ribavirin. [4],[5] Psychiatric symptoms have also been reported in few patients in the form of major depression, anxiety, irritability, insomnia, and suicidal ideation, forcing the discontinuation of IFN-α therapy. [1],[6],[7] So far, there are no studies which examine the relationship between viral load and patient-related depression. [3] Ribavirin itself does not appear to have a significant effect on mood, but adverse effects of IFNs appear to be potentiated. [8] In our case, the patient had no history suggestive of depression, as reported by patient and his family. Even patient′s psychosocial factors did not favor any cause leading to suicidal attempt. Antidepressant treatment given concomitantly with IFN-α and ribavirin was not found to be as effective. In our patient, symptoms of depression regressed after withdrawal of IFN-α-2a and ribavirin and reappeared after reintroduction of IFN-α and ribavirin. Naranjo causality assessment score suggested probable relationship between combination (IFN-α and ribavirin) and depression leading to suicidal attempt. This depression differs from major depression in relation to response to antidepressants. There are few reports supporting this fact. [5],[9],[10] Even IFNs have been reported to increase the levels of catecholamines and cortisol and modify the levels of endogenous opioids and 5-HT. [11] In one study, platelet 5-HT level has been found to decrease significantly in IFN-treated patients, which may probably be responsible for depressive symptoms. [12] Understanding the relationships among HCV, IFN, and depression is critical to provide effective treatment to patients with HCV. Also, psychiatric consultation before IFN-α and ribavirin combination therapy can be helpful in better compliance of patients toward treatment. [4] It is suggested that IFN-α and ribavirin should be withdrawn in patients showing symptoms of depression and suicidal ideation because impulsive suicidal attempt has been reported with cytokine-related therapy. [13] Antidepressants should be started with close monitoring of patient′s symptoms. Further studies are needed to explore when to discontinue or continue IFN-α and ribavirin therapy in patients with HCV infection and also the long-term safety of antidepressant drug therapy in these patients. References
Copyright 2011 - Indian Journal of Pharmacology |
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