The treatment of iron overload — psychiatric implications

  • M. Struck
  • P. Waldmeier
  • V. Berdoukas
Part of the Key Topics in Brain Research book series (KEYTOPICS)


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.


Iron Overload Porphyria Cutanea Tarda Iron Excretion Active Iron Chelator Oral Iron Chelator 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Ackrill P, Day JP (1985) Desferrioxamine in the treatment of aluminum overload. Clin Nephrol 24 [Suppl] 1: S94 - S97Google Scholar
  2. Ackrill P, Ralston AJ, Day JP, Hodge KC (1980) Successful removal of aluminum from patient with dialysis encephalopathy. Lancet 11: 692–693CrossRefGoogle Scholar
  3. Agarwal MB, Gupte SS, Viswanathan C, Vasandani D, Ramanathan J, Neena Desai, Puniyani RR, Chhablani AT (1992) Long-term assessment of efficacy and safety of L1, an oral iron chelator, in transfusion dependant thalassaemia: Indian trial. Br J Haematol 82: 460–466PubMedCrossRefGoogle Scholar
  4. Aldrich RA (1958) Acute iron toxicity. In: Wallerstein RO, Mettier SR (eds) Iron in clinical medicine. University of California Press, Berkeley, p 93Google Scholar
  5. Arze RS, Parkinson IS, Cartlidge NEF, Britton P, Ward MK (1981) Reversal of aluminum dialysis encephalopathy after desferrioxamine treatment. Lancet 11: 1116CrossRefGoogle Scholar
  6. Ben-Shachar D, Riederer P, Youdim MBH (1991) Iron-melanin interaction and lipid peroxidation: implications for Parkinson’s disease. J Neurochem 57: 1609–1614PubMedCrossRefGoogle Scholar
  7. Ben-Shachar D, Eshel G, Riederer P, Youdim MBH (1992) Role of iron and iron chelation in dopaminergic-induced neurodegeneration: implications for Parkinson’s disease. Ann Neurol 32 [Suppl]: 105–110CrossRefGoogle Scholar
  8. Bentur Y, McGuigan M, Koren G (1991) Deferoxamine (Desferrioxamine): new toxicities for an old drug. Drug Safety 6 1: 37–46PubMedCrossRefGoogle Scholar
  9. Boyce N, Wood C, Holdsworth S, Thomson NM, Atkins RC (1985) Life threatening sepsis complicating heavy metal chelation therapy with desferrioxamine. Aust NZ J Med 15 5: 654–655Google Scholar
  10. Castriota Scanderbeg A, Izzi GC, Butturini A, Benaglia G (1990) Pulmonary syndrome and intravenous high-dose desferrioxamine. Lancet 336: 1611Google Scholar
  11. Cohen A, Martin M, Mizanin J, Konkle DF, Schwartz E (1991) Vision and hearing during deferoxamine therapy. J Pediatr 117 2: 26–330Google Scholar
  12. Crapper McLachlan DR, Dalton AJ, Kruck TP, Bell MY, Smith WL, Kalow W, Andrews DF (1991) Intramuscular desferrioxamine in patients with Alzheimer’s disease. Lancet 337 (8753): 1304–1308CrossRefGoogle Scholar
  13. Cutler P (1991) Iron overload in psychiatric illness. Am J Psychiatry 148 1: 147–148PubMedGoogle Scholar
  14. Dexter Dt, Carter CJ, Wells FR, Javoy-Agid F, Lees A, Jenner P, Marsden CD (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem 52: 381–389PubMedCrossRefGoogle Scholar
  15. Gentsch C, Vassout A, Mondadori C (1992) CNS evaluation of CGP 37 391 ( L1 ). CIBA Internal ReportGoogle Scholar
  16. Henretig FM, Temple AR (1984) Acute iron poisoning in children. Clin Lab Med 4 3: 575–586PubMedGoogle Scholar
  17. Hershko C, Weatherall DJ (1988) Iron-chelating therapy. CRC Crit Rev Clin Lab Sci 26 4: 303–345CrossRefGoogle Scholar
  18. Hirsch E, Graybiel Am, Agid YA (1988) Melanized dopaminergic neurones are differently susceptible to degeneration in Parkinson’s disease. Nature 334: 345–348PubMedCrossRefGoogle Scholar
  19. Idjradinata P, Pollitt E (1993) Reversal of developmental delays in iron-deficient anaemic infants treated with iron. Lancet 341 (8836): 1–4PubMedCrossRefGoogle Scholar
  20. Kaplan HI, Sadock BJ (1991) Synopsis of psychiatry, behavioral sciences. In: Clinical psychiatry, 6th edn. Williams & Wilkins, Baltimore, p 211Google Scholar
  21. Marciani MG, Cianiulli P, Stefani N, Stefanini F, Peroni L, Sabbadini M, Maschio M, Trua G, Papa G (1991) Toxic effects of high-dose deferoxamine treatment in patients with iron overload: an electrophysiological study of cerebral and visual function. Haematologica 76, 2: 131–134PubMedGoogle Scholar
  22. Modell B, Berdoukas V (1984) The clinical approach to thalassaemia. Grune & Stratton (Harcourt Brace Jovanovich)Google Scholar
  23. Olivieri NF, Koren G, Hermann C, Bentur Y, Chung D, Klein J, St. Louis P, Freedman MH, McClelland RA, Templeton DM (1990) Comparison of oral iron chelator L1 and desferrioxamine in iron-loaded patients. Lancet 336: 1275–1279Google Scholar
  24. Porter JB, Huehns ER (1989) The toxic effects of desferrioxamine. Bailliere’s Clin Haematol 22: 459–474CrossRefGoogle Scholar
  25. Porter JB, Huehns ER, Hider RC (1989) The development of iron chelating drugs. Bailliere’s Clin Haematol 22: 257–292CrossRefGoogle Scholar
  26. Shoulson I (1992) Neuroprotective clinical strategies for Parkinson’s disease. Ann Neurol 32 [Suppl]: 143–145CrossRefGoogle Scholar
  27. Sofic E, Paulus W, Jellinger K, Riederer P, Youdim MPH (1991) Selective increase of iron in substantia nigra zona compacta of parkinsonian brains. J Neurochem 56: 978–982PubMedCrossRefGoogle Scholar
  28. Taylor RJ, Stubbs CS, Ellenbogen L (1969) Tyrosine hydroxylase inhibition in vitro and in vivo by chelating agents. Biochem Pharmacol 18: 587–594PubMedCrossRefGoogle Scholar
  29. Waldmeier P, Buchle AM, Steulet AF (1993) The orally active iron chelator, 1,2dimethyl-3-hydroxypyridin-4-one (LI, CP 20) inhibits COMT as well as tyrosine and tryptophan hydroxylase in rat brain in vivo. Biochem PharmacolGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1993

Authors and Affiliations

  • M. Struck
    • 1
  • P. Waldmeier
    • 2
  • V. Berdoukas
    • 3
  1. 1.Clinical Research and Development CNSK-147.P.09 Ciba Ltd.BaselSwitzerland
  2. 2.Research Department CNSCiba Ltd.BaselSwitzerland
  3. 3.Clinical Research and Development IT/OTACiba Ltd.BaselSwitzerland

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