A case of intractable psychosis following interferon therapy

To the Editor

Prior to the development of novel antiviral agents, pegylated interferon-alpha (IFN-α) was the cornerstone of treatment for chronic hepatitis C. Neuropsychiatric disturbances, though rarely psychotic disorders, have been reported with IFN-α use (Ganeshalingam et al., 2009). Psychiatric symptoms typically manifest during treatment and resolve within 6 months of treatment withdrawal (Huckans et al., 2015). We present a case of suicidality driven by psychosis persisting for 10 years following discontinuation of IFN-α therapy.

Mr S is a 38-year-old man with a remote history of intravenous heroin use, diagnosed with HIV and hepatitis C for which he was started on IFN-α at the age of 28 years. He was a lawyer at the time and described by family as an outgoing and lively individual.

After 10 months of IFN-α therapy, he began experiencing paranoia, persecutory delusions and ideas of reference. IFN-α was stopped. He was briefly hospitalized and treated with risperidone, which he discontinued after a year. His family described him as ‘never the same’ since this episode of psychosis.

Three years later, he had a second episode of psychosis similar to the first and abruptly left his wife and son to travel the world. In the years following, he carried out multiple suicide attempts and acts of self-mutilation, including an attempt to freeze to death in the Arctic Circle resulting in hand amputation by frostbite, self-enucleation of his eye with a retractable knife and jumping onto the path of an oncoming train on three occasions, resulting in loss of his left leg and right toes. In his words, these acts were efforts to ‘make [himself] stronger, psychologically’.

He eventually presented to our hospital in 2018, brought in by family following a 6-month hospitalization in Europe without improvement. He displayed no significant positive symptoms of psychosis, but had marked negative symptoms of paucity of thought, flat and incongruent affect, monotonous voice and avolition. Mr S was started on clozapine and lithium given his high suicide risk. Two months later, these symptoms remained minimally responsive to treatment.

This case of IFN-induced psychosis aligns well with previously reported cases in terms of symptomatology, with suicidality and predominance of persecutory delusions and paranoia (Nozaki et al., 1997). In this patient with no personal or family psychiatric history, and no prodrome preceding his psychotic break at the age of 28 years, it is possible that his persistent psychosis is long-term sequelae of IFN-α therapy. As such, we must be aware that the neurotoxicity of IFN-α may be longer lasting and of greater severity than previously reported.