Is there a rationale for iron supplementation in the treatment of akathisia? A review of the evidence.

BACKGROUND

An association found between akathisia and iron deficiency led to the suggestion that iron supplementation might be a useful therapeutic intervention for patients with akathisia. There is, however, a body of literature on the abnormal deposition of iron in the brain in several degenerative diseases like Hallervorden-Spatz syndrome, Parkinson's disease, and Alzheimer's disease. Given the ability of neuroleptics to chelate iron and promote its deposition in the brain, we questioned whether peripheral measures of iron are an accurate reflection of central iron levels and thus whether there was a rationale for iron supplementation in akathisia.

METHOD

A MEDLINE search for literature relating to iron and akathisia, tardive dyskinesia, and Parkinson's disease was carried out and critically reviewed.

RESULTS

Evidence is presented for the ability of neuroleptics to chelate iron, mobilize it from peripheral stores, and deposit it in the basal ganglia. The effect of iron on dopaminergic receptor activity in brain and the potential role of iron in degenerative and neuroleptic-induced movement disorders are reviewed. The preponderance of the evidence shows a relationship between iron excess in the basal ganglia and the movement disorders. We found no studies that have examined the regulation of central levels of iron in patients with akathisia.

CONCLUSION

The rationale for iron supplementation in the treatment of akathisia is relatively weak, and there are potentially adverse long-term consequences as outlined in our review. More research is required to directly measure the level of iron in the brain of patients with akathisia, e.g., using magnetic resonance imaging, before such therapeutic intervention can be recommended.