Permanent non-progressive cinnarizine and flunarizine-induced parkinsonism: An under-recognized tardive syndrome in the elderly?

Abstract

Secondary parkinsonism induced by exposure to dopamine (DA) receptor antagonists as first and second generation antipsychotics, DA storage depleters, calcium channel blockers, benzamides substituted and other classes of drugs is traditionally believed to be completely reversible in most of patients following withdrawal of the offending drug even though after a variable time delay. The lack of recovery or initial full recovery with subsequent development of progressive parkinsonism has been regarded to result from an underlying subclinical degenerative process like PD unmasked by the inducing drug. These well-recognized clinical outcomes of drug-induced parkinsonism (DIP) have disregarded the existence of another outcome, characterized by permanent non-progressive parkinsonism. This syndrome may fullfil the criteria of tardive parkinsonism, a controversial entity currently referred to as a persistent condition without indication of its long-term course and clinical features. On reviewing the published literature on DIP, we have identified two prospective long-term follow-up of elderly patients in which parkinsonism induced by the calcium channel antagonists cinnarizine and flunarizine became permanent and non-progressive following drug discontinuation in a non-negligible proportion of patients, consistent with the clinical concept of a true tardive syndrome, according to currently accepted criteria. The authors hypothesize that the development of tardive parkinsonism might be due to a neurotoxic effect of the pharmacodynamic proprieties of the calcium channel blockers and their metabolites, exerted on post-synaptic striatal neurons and/or a neurotoxic damage on presynaptic DA neurons in patients without an underlying subclinical degenerative parkinsonism, so accounting for the stable and non-progressive course over time.

• Authors: Stefano Calzetti, Anna Negrotti
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 444 Pg. 120526 (01 15 2023) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 36584558 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Flunarizine
• Cinnarizine
• Calcium Channel Blockers
• Dopamine Antagonists
• Antipsychotic Agents

Topics

• Humans
• Aged
• Flunarizine (adverse effects)
• Cinnarizine (adverse effects)
• Calcium Channel Blockers (adverse effects)
• Prospective Studies
• Parkinsonian Disorders (chemically induced)
• Parkinson Disease, Secondary (chemically induced)
• Dopamine Antagonists (adverse effects)
• Antipsychotic Agents (adverse effects)
• Syndrome