PEG-interferon-α

Reactions 1007 - 26 Jun 2004 ★ S PEG-interferon-α First report of mania: case report A 39-year-old man developed psychotic mania after starting treatment with PEG-interferon-α and ribavirin for chronic hepatitis C virus infection. The man, who had a history of injection drug use, diabetes mellitus and depression, had previously been treated with interferon-α and ribavirin, but had developed sadness, tearful episodes, fatigue and a flu-like syndrome. His fluoxetine dosage had been increased, his mood had improved and, 4 months later, he was switched to PEG-interferon-α and ribavirin. During the therapy switch, he missed enough doses of interferon-α and ribavirin to take a drug holiday, and his fatigue and flu-like symptoms remitted. Within 3 weeks of starting once-weekly PEG-interferon-α 180µg and ribavirin 1200mg injections, he developed restlessness, insomnia and episodes of unprovoked laughter, tearfulness and irritability. His symptoms evolved into euphoria, increased libido, impulsive generosity, excessive religiousness, thought disorder, grandiose delusions, ideas of reference and delusions of external control by telepathy and mobile telephone. He was instructed by his hepatologist to stop PEG- interferon-α and ribavirin, but continued the medication; after almost 2 weeks of psychosis, he was taken to the emergency room in a state of agitation and disorganisation. The man received haloperidol and diphenhydramine, and was admitted to hospital. He was euphoric, grandiose and talkative with loose associations. He denied hallucinations, aggressive impulses and suicidal or homicidal ideation. Delusions were not elicited and he did not have phobias, obsessions or compulsions. He showed poor insight and judgement and was unable to answer questions on the Mini- Mental State Examination. A physical examination was unremarkable, and his vital signs were normal. He was diagnosed with a manic episode of bipolar I disorder, possibly triggered by PEG-interferon-α. PEG-interferon-α, ribavirin, fluoxetine and zolpidem were discontinued and haloperidol was started. The next day, the man received benzatropine for mild dystonia and the haloperidol dosage was decreased and, on hospital day 2, lithium was started. By hospital day 3, his mania had remitted and his lithium dosage was increased. On day 4, haloperidol was discontinued and he was discharged. One week after discharge, his manic symptoms had resolved; the episode of mania was diagnosed as a substance-induced mood disorder associated with PEG-interferon-α. He discontinued lithium a few weeks later, and remained stable during follow-up. Author comment: "Ultimately, the precise mechanisms involved in the evolution of mania during interferon treatment remain a matter of speculation, but several lines of evidence have pointed to neuroendocrine, neurotransmitter, and cytokine pathways." Onyike CU, et al. Mania during treatment of chronic hepatitis C with pegylated interferon and ribavirin. American Journal of Psychiatry 161: 429-435, No. 3, Mar 2004 - USA 800974784 » Editorial comment: A search of AdisBase and Medline did not reveal any previous case reports of mania associated with PEG-interferon-α. The WHO Adverse Drug Reactions database contained one report of manic reaction associated with PEG- interferon-α2-a. 1 Reactions 26 Jun 2004 No. 1007 0114-9954/10/1007-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved

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Transcript of PEG-interferon-α

Reactions 1007 - 26 Jun 2004

★ SPEG-interferon-αFirst report of mania: case report

A 39-year-old man developed psychotic mania after startingtreatment with PEG-interferon-α and ribavirin for chronichepatitis C virus infection.

The man, who had a history of injection drug use, diabetesmellitus and depression, had previously been treated withinterferon-α and ribavirin, but had developed sadness, tearfulepisodes, fatigue and a flu-like syndrome. His fluoxetinedosage had been increased, his mood had improved and,4 months later, he was switched to PEG-interferon-α andribavirin. During the therapy switch, he missed enough dosesof interferon-α and ribavirin to take a drug holiday, and hisfatigue and flu-like symptoms remitted. Within 3 weeks ofstarting once-weekly PEG-interferon-α 180µg and ribavirin1200mg injections, he developed restlessness, insomnia andepisodes of unprovoked laughter, tearfulness and irritability.His symptoms evolved into euphoria, increased libido,impulsive generosity, excessive religiousness, thoughtdisorder, grandiose delusions, ideas of reference anddelusions of external control by telepathy and mobiletelephone. He was instructed by his hepatologist to stop PEG-interferon-α and ribavirin, but continued the medication; afteralmost 2 weeks of psychosis, he was taken to the emergencyroom in a state of agitation and disorganisation.

The man received haloperidol and diphenhydramine, andwas admitted to hospital. He was euphoric, grandiose andtalkative with loose associations. He denied hallucinations,aggressive impulses and suicidal or homicidal ideation.Delusions were not elicited and he did not have phobias,obsessions or compulsions. He showed poor insight andjudgement and was unable to answer questions on the Mini-Mental State Examination. A physical examination wasunremarkable, and his vital signs were normal. He wasdiagnosed with a manic episode of bipolar I disorder, possiblytriggered by PEG-interferon-α.

PEG-interferon-α, ribavirin, fluoxetine and zolpidem werediscontinued and haloperidol was started. The next day, theman received benzatropine for mild dystonia and thehaloperidol dosage was decreased and, on hospital day 2,lithium was started. By hospital day 3, his mania had remittedand his lithium dosage was increased. On day 4, haloperidolwas discontinued and he was discharged. One week afterdischarge, his manic symptoms had resolved; the episode ofmania was diagnosed as a substance-induced mood disorderassociated with PEG-interferon-α. He discontinued lithium afew weeks later, and remained stable during follow-up.

Author comment: "Ultimately, the precise mechanismsinvolved in the evolution of mania during interferontreatment remain a matter of speculation, but several lines ofevidence have pointed to neuroendocrine, neurotransmitter,and cytokine pathways."Onyike CU, et al. Mania during treatment of chronic hepatitis C with pegylatedinterferon and ribavirin. American Journal of Psychiatry 161: 429-435, No. 3, Mar2004 - USA 800974784

» Editorial comment: A search of AdisBase and Medline didnot reveal any previous case reports of mania associated withPEG-interferon-α. The WHO Adverse Drug Reactions databasecontained one report of manic reaction associated with PEG-interferon-α2-a.