Psychiatric Side Effects of Treatment with Interferon-alpha in Oncology Patients

Treatment with the cytokine interferon-α (IFN-α) is associated with a wide array of side effects including psychiatric side effects, most notably depressive symptoms and syndromes. In this thesis, both the somatic and the psychiatric side effects, their presumed pathophysiology, and the strategies to handle them are reviewed. Biochemical parameters possibly underlying IFN-α induced mood disorder were investigated. Treatment with IFN-α decreased tryptophan blood levels and the availability of tryptophan to the brain, possibly inducing diminished serotonin synthesis in the brain. The degradation of tryptophan to kynurenin was increased and as several of the breakdown products of kynurenin are presumed to be neurotoxic, this could contribute to psychiatric side effects. In addition, treatment with IFN-α consistently increased blood concentrations of neopterin, possibly leading to shortage of tetrahydrobiopterin, an essential co-factor in the biosynthesis of serotonin. Although concentrations of biopterin, the metabolite of tetrahydrobiopterin, did not change, the conversion of phenylalanine to tyrosine, in which tetrahydrobiopterin is also a co-factor, was diminished. Activity of monoamine oxidase (MAO) in platelets increased during therapy with IFN-α. Increased MAO activity in the brain possibly increases breakdown of serotonin. Finally, we found decreased activity of prolyl endopeptidase (PEP) during therapy with IFN-α, a enzyme possibly involved in the breakdown of psychoactive peptides. The activity of the exopeptidase dipeptidyl peptidase-IV (DPP-IV) did not change. In our clinical research, despite the changes in the aforementioned laboratory parameters, the incidence of IFN-α-induced depression was lower than expected and few clinically relevant mood disorders bearing a probable relationship with IFN-α occurred. We conclude, that treatment with the used doses of IFN-α in oncology patients is not a suitable research model into the treatment of mood disorders and that the observed changes in laboratory parameters do not induce psychiatric disorder.