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Year : 2006  |  Volume : 52  |  Issue : 3  |  Page : 207-209

Mania associated with interferon α2b treatment

Department of Psychiatry, Christian Medical College, Vellore - 632 002, Tamil Nadu, India

Correspondence Address:
K K Basanth
Department of Psychiatry, Christian Medical College, Vellore - 632 002, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

PMID: 16855324

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 :: Abstract 

Neuropsychiatric side effects are common with Interferon α 2b. Psychosis and depression have been reported. Several cases of mania have been reported but only few have been associated with treatment for hepatitis B. We report a case of mania with psychotic symptoms in a 21-year-old female diagnosed to have hepatitis-B infection, who was receiving interferon. The report supports the view that dose reductions or pauses during interferon treatment can cause mania. Family history of mood disorder could be a risk factor. Atypical presentations are common in interferon-induced mania. Mania induced by interferon responds well to antimanic drugs. Since the use of interferon is increasing in developing countries, the need for awareness of side effects and management issues are important and these are highlighted.

Keywords: Interferon, psychosis, mania, lithium.

How to cite this article:
Basanth K K, Jacob R, Jacob K S. Mania associated with interferon α2b treatment. J Postgrad Med 2006;52:207-9

How to cite this URL:
Basanth K K, Jacob R, Jacob K S. Mania associated with interferon α2b treatment. J Postgrad Med [serial online] 2006 [cited 2023 Jun 9];52:207-9. Available from:

Interferon α 2b has been widely used as a treatment option for several types of cancers and chronic hepatitis.[1],[2],[3] Neuropsychiatric side effects are common and sometimes serious.[1],[2],[3] Documented morbidity includes anxiety, irritability, depression (including suicide), psychosis, delirium and mania.[1],[2],[3] Mood disorders have been noted frequently in patients treated with interferon α 2b.[1],[2],[3] Depression is the most common comorbid disorder described.[1] Several cases of mania have been reported but only a few have been associated with treatment for hepatitis B. [2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13]

 :: Case History Top

A 21-year-old single female was diagnosed to have hepatitis B infection in the gastroenterology department of our hospital. She gave a family history of bipolar disorder in a sibling. There was no history of psychiatric illnesses, including substance abuse in the past. Her physical examination was normal. She was started on interferon α 2b, five million units, to be given subcutaneously, on alternate days. Compliance to injections was poor, probably due to fever and depressive symptoms after the first three doses. Abnormal behavior was noticed after reintroduction of interferon on day 20. [Table - 1] shows the events starting from the first dose of interferon unto her referral to the psychiatric emergency department and further management until she reached euthymic status.

Mental status examination, on day 23, revealed increased psychomotor activity, irrelevant talk, fleeting persecutory and grandiose delusions. She denied perceptual disturbances. Her affect was irritable and labile. She was oriented and her memory was intact. Judgment was impaired and she denied having any mental illness and denied need for any treatment. A provisional diagnosis of acute polymorphic psychotic disorder with symptoms of schizophrenia was made.[14] She was admitted to the hospital for observation and management. She was managed on day 23 with increasing doses of risperidone and lorazepam (for control of agitation).

She was administered interferon α 2b on day 24, after which the symptoms worsened. Her mood was elated, psychomotor activity was increased; she talked excessively, was spontaneous and thought-content revealed grandiose delusions. There was no waxing-waning course or other evidence of delirium. The diagnosis was changed to organic mood disorder.[14] Interferon α 2b was suspected to be the cause and administration of the same was stopped. Lithium was started after the diagnosis was revised. She reached euthymic status on day 35. She could recall the mood state and psychotic symptoms after she became euthymic. She also recalled feeling depressed a few days following the first three doses but on retrospective clarification, it did not fulfill criteria for a major depressive episode. Lorazepam was tapered and stopped before she was discharged.

WBC counts had dropped to 3200 cells/cumm one day after interferon was restarted. In view of possibility of reduced WBC counts with interferon treatment, no specific treatment was initiated and WBC counts were monitored regularly. Other biochemical changes suggestive of interferon α 2b toxicity or adverse effects were not present. Symptoms or signs suggestive of intoxication or withdrawal due to substance use were not observed during the entire period of hospitalization.

 :: Discussion Top

Firstly, minor changes in mood, especially depressed mood reported very often in literature, were present after the first three doses, which could have contributed to discontinuation of interferon treatment. Secondly, psychotic symptoms started when interferon was reintroduced two weeks after the third dose. Thirdly, improvement was seen after antipsychotics were started. Fourthly, worsening of manic symptoms and grandiose delusion occurred immediately after interferon was restarted for the second time, this in spite of the patient being on risperidone and lorazepam. WBC counts, which had dropped, had improved to normal levels and this can happen with interferon treatment. Lastly, symptoms subsided in ten days after interferon was withheld and adequate pharmacotherapy was instituted. The sequence of events described suggests that the mental illness was secondary to treatment with interferon. The score on Naranjo's algorithm is six, which means there is a probable association between the mania and interferon treatment.[15]

This report adds to the literature implicating interferon α 2b treatment in the production of mania. [1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13] Points concurring with earlier reports are a) Modifications in doses such as reductions and pauses seem to play a role.[3] b) Atypical presentations are common.[3] c) Mood symptoms are variable and may change over time.[1],[2],[3] d) Family and personal history of mood disorder might be a risk factor for developing mania during treatment with interferon α 2b.[1],[2],[3] e) There is definite improvement with discontinuation of interferon α 2b and initiation of treatment for mania.[1],[2],[3] f) In addition, most reports have described resolution of manic symptoms in one month following treatment.[2]

The use of interferon is gradually increasing in developing countries and the resulting neuropsychiatric side effects are bound to increase. Early detection and treatment has to be stressed for all physicians, as different specialties are involved in the detection and treatment process. Evaluating pharmacologic prevention and treatment, both short term and long term, of interferon-induced mania are to be given priority. A high rate of mood disorders may suggest the need for prophylaxis with a mood stabilizer in order to prevent such episodes of mental illness. Formulating criteria for reinstitution of interferon therapy after development of mania is imperative. Systematic studies evaluating the mechanism of action responsible for the interferon α 2b-induced mania, which is yet unidentified is necessary.

 :: References Top

1.Raison CL, Demetrashvilli M, Capuron L, Miller AH. Neuropsychiatric adverse effects of interferon-alpha: Recognition and management. CNS Drugs 2005;19:105-23.  Back to cited text no. 1    
2.Onyike CU, Bonner JO, Lyketsos CG, Treisman GJ. Mania during treatment of chronic hepatitis C with pegylated interferon and ribavirin. Am J Psychiatr 2004;61:429-35.  Back to cited text no. 2    
3.Greenberg DB, Jonasch E, Gadd MA, Ryan BF, Everett JR, Sober AJ, et al . Adjuvant therapy of melanoma with interferon-alpha-2b is associated with mania and bipolar syndromes. Cancer 2000;89:356-62.  Back to cited text no. 3    
4.Altindag A, Ozbulut O, Ozen S, Ucmak H. Interferon-alpha-induced mood disorder with manic features. Gen Hosp Psychiatr 2001;23:168-70.  Back to cited text no. 4    
5.Carpiniello B, Orru MG, Baita A, Pariante CM, Farci G. Mania induced by withdrawal of treatment with interferon alfa. Arch Gen Psychiatr 1998;55:88-9.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Howes OD, McKenzie KJ. Manic psychosis induced by long term alpha - interferon treatment for hepatitis. Int J Psychiatr Clin Pract 2000;4:161-2.  Back to cited text no. 6    
7.Iancu I, Sverdlik A, Dannon PN, Lepkifker E. Bipolar disorder associated with interferon-alpha treatment. Postgrad Med J 1997;73:834-5.  Back to cited text no. 7  [PUBMED]  
8.Kanno A, Yamada M, Abe M, Okamoto Y. A case of interferon [alpha]-induced manic psychosis in chronic hepatitis C. Tohuku J Exp Med 1999;187:79-82.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Kingsley D. Interferon-alpha induced 'tertiary mania'. Hosp Med 1999;60:381-2.  Back to cited text no. 9  [PUBMED]  
10.Malik AR, Ravasia S. Interferon-induced mania. Can J Psychiatr 2004;49:867-8.  Back to cited text no. 10    
11.Monji A, Yoshida I, Tashiro K, Hayashi Y, Tashiro N. A case of persistent manic depressive illness induced by interferon-alfa in the treatment of chronic hepatitis C. Psychosomatics 1998;39:562-4.  Back to cited text no. 11    
12.Rossi A, Renzetti D, D'Albenzio L, Gianfelice D, Kalyvoka A, Rinaldi O. Case of mania induced by withdrawal of interferon-alpha in a patient affected by bipolar disorder. Psychiatr Clin Neurosci 2002;56:647-8.  Back to cited text no. 12    
13.Strite D, Valentine AD, Meyers CA. Manic episodes in two patients treated with interferon [alpha]. J Neuropsychiatr Clin Neurosci 1997;9:273-6.  Back to cited text no. 13    
14.World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic criteria for research. WHO: Geneva; 1992.  Back to cited text no. 14    
15.Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al . A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 15    


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2004 - Journal of Postgraduate Medicine
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