The treatment of iron overload — psychiatric implications

Summary

The introduction of the iron-chelator deferoxamine in the treatment of acute iron poisoning and various chronic iron overload states such as beta-thalassaemia major has dramatically improved the prognosis of patients affected. The outcome of long-term treatment, however, heavily relies on patient compliance, which is a particular problem with a chelating agent that optimally has to be given as a s.c. infusion over several hours a day. Thus the availability of a safe and orally active iron chelator would be a major achievement.

Little is known about the effects of iron and of iron chelation therapy in the field of neuropsychiatry. It has been postulated, however, that iron-chelating agents may prevent or halt degeneration of dopaminergic neurones in patients suffering from Parkinson’s disease. Iron is known to have an impact on the formation of neurotoxic free radicals.

New data, both clinical and preclinical, on the orally active iron chelator CGP 37 391 indicate, that the compound has the ability to achieve a negative iron balance in man in combination with a problematic tolerability profile. In rat it penetrates the blood-brain barrier and is a potent tyrosine and tryptophan hydroxylase inhibitor, which renders the hypothesis of being of value in Parkinson’s disease unlikely. In contrast orally active bidentate iron-chelators may well represent a novel approach in the treatment of schizophrenia, if compounds with excellent tolerability can be found.