Psychological side effects of immune therapies: symptoms and pathomechanism

- Most frequent side-effect of long-term interferon-alpha treatment is depression.
- Immunotherapy-induced depression is characterised by neurovegetative symptoms.
- Immunotherapy-induced depression can be prevented or treated by SSRIs.
- But high level inflammation in major depression predicts treatment resistance.

Immunotherapies revolutionised the treatment of several disorders but show specific side-effect profiles which frequently involve psychological symptoms. Long term interferon-alpha (IFN-alpha) therapy can cause wide-ranging psychiatric side-effects from fatigue, insomnia, anxiety to full-blown depression. This treatment-emergent depression shares several symptoms with major depressive disorder (MDD) with a predominance of somatic/neurovegetative symptoms, and can be treated with antidepressants. However, this experience directed research to inflammatory mechanisms in MDD. MDD has been confirmed as a heterogeneous disorder with a subgroup of patients suffering from low-grade chronic inflammation and frequently resistant to traditional antidepressant treatment. Thus future research should develop strategies to identify those MDD patients who could benefit from drugs acting through inflammatory pathways.