Abstract
Interferon belongs to a class of glycoproteins known as cytokines. Interferon alpha (IFN-α) has been shown to be effective in the treatment of hepatitis C in combination with ribavirin [1]. Neuropsychiatric side effects are not uncommon with IFN-α treatment and include anxiety and depression, but rarely psychosis, delirium and mania [2]. We present a case of mania following IFN-α treatment in a patient with hepatitis C and schizophrenia. The literature indicates that mania can occur in 1–2% of patients receiving IFN-α therapy [3].
The patient is a 26 year old man with a history of drug abuse before the onset of schizophrenia at age 20 in 2004. The patient experienced recurrent episodes of psychosis (persecutory delusions) exacerbated by persistent THC abuse. He required maximal doses of risperidone to control his persistent psychosis. In October 2007 he had an episode of depression which resolved with the antidepressant citalopram. Citalopram was only prescribed for several months then ceased. There was no past history of mania/hypomania or a genetic predisposition suggestive of a bipolar disorder. In July 2009, risperidone was replaced with aripiprazole 20 mg with the complete resolution of his psychosis. In November the same year he was diagnosed with hepatitis C and referred for IFN-α treatment.
In April 2010 the patient commenced weekly IFN-α therapy while being maintained on aripiprazole. He remained clinically stable until August 2010 when he developed symptoms of hypomania. In November 2010 he was admitted to an inpatient unit because of an increase in the severity of his manic symptoms. He was noted to have poor sleep, increased energy levels and marked agitation with pressured speech. The patient was compliant with his aripiprazole and had not taken any illicit drugs while on IFN-α. His schizophrenia was in remission.
The patient was diagnosed with a manic episode and started on sodium valproate and lorazepam in addition to his aripriprazole. He remained manic for 2 weeks and a gastroenterology consult was sought with a view to ceasing IFN-α as it was suspected to be implicated in his mania.
Two weeks after ceasing IFN-α, the patient's manic symptoms improved and he was discharged home on sodium valproate and aripriprazole. However, he remained hypomanic in the community for 3 months before reaching a state of remission. He has remained well since.
This patient scored 6 on the Naranjo and colleagues' Adverse Drug Reaction Scale [4], thus implicating IFN-α as a probable cause for the mania.
The mechanism of how IFN-α induces mania is still unknown. Some possible etiologies include interferon-induced changes in thyroid function, direct stimulation or inhibition of the hypothalamic–pituitary axis, indirect effects of IFN-α on the opioid receptor system, interferon-mediated alterations in neurotransmitter levels and toxic effects of secondary cytokines [5].
This report adds to a small but growing number of cases implicating IFN-α treatment in the precipitation of mania. This case report differs from other published reports in that maintenance antipsychotic medication (aripiprazole) did not sufficiently provide prophylaxis against manic symptoms but prevented an exacerbation of his psychosis. This case highlights the delayed onset of mania following initiation of IFN-α and the resolution of manic symptoms, which could take several months even after its cessation.