Psychosis is an uncommon but serious complication of treatment with interferon-α, a cytokine frequently used to treat several infectious and malignant diseases.

To provide an overview of interferon-α-induced psychosis.

Literature review based on PubMed/MEDLINE, using the keywords “interferon-α” and “psychosis”.

Psychotic symptoms usually emerge between 6 to 46 weeks and on average 3 months after the start of interferon-α treatment, occurring most frequently in the form of persecutory, guilt or grandeur delusions and auditory hallucinations. Often they are accompanied by mood symptoms, anxiety, attention disturbances and insomnia. Many factors are known to increase the risk of psychiatric effects as a whole associated with interferon-α. Pathogenesis of interferon-induced psychosis remains unclear, however several theories have been discussed, namely the overlap influence of biological vulnerability and the cytokine's action on the brain. Dopaminergic, opioid, serotoninergic and glutaminergic pathways as well as hypothalamic-pituitary-adrenal axis hypersensitivity are some of the hypotheses raised about the underlying cause of that susceptibility. Psychosis management usually includes stopping interferon-α and introducing antipsychotics with minimal antidopaminergic effects and at the lowest possible dose, due to the increased risk of extrapyramidal reactions in these patients.

The decision to use interferon-based treatments in psychiatric patients should be highly individualized. Early recognition and adequate treatment of interferon-induced psychosis might prevent subsequent emergence of serious debilitating symptoms. Thus, it is very important that medical and psychiatric treatment teams work closely together and are familiar with this important subject.