Parkinsonism following neuroleptic exposure: A double-hit hypothesis?

Mov Disord. 2015 May;30(6):780-5. doi: 10.1002/mds.26209. Epub 2015 Mar 18.


Drug-induced parkinsonism is caused by an offending drug and should resolve after the causative agent has been withdrawn. However, in a number of patients, symptoms persist or may even worsen over time, suggesting the development of concomitant Parkinson's disease. The prevalence estimates of Parkinson's disease after neuroleptic exposure are unexpectedly high, suggesting a causal relationship. We critically review available literature in this regard, and some pathophysiological hypotheses that might explain such a relationship are suggested. Some patients may have an undetermined genetic susceptibility to parkinsonism. We speculate that the possible neurotoxic effect of neuroleptics exerted on a susceptible dopaminergic system would lead over the long-term to a self-fostering, progressive process. Knowledge gaps and future perspectives are discussed.

Keywords: Parkinson's disease; anti-pychotics; drug-induced parkinsonism; neuroleptics; pathophysiology.

Publication types

  • Review

MeSH terms

  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / toxicity*
  • Brain / drug effects*
  • Brain / physiopathology
  • Genetic Predisposition to Disease
  • Humans
  • Parkinson Disease / epidemiology
  • Parkinson Disease / etiology*
  • Parkinson Disease / physiopathology
  • Parkinson Disease, Secondary / chemically induced*
  • Parkinson Disease, Secondary / physiopathology
  • Prevalence
  • Risk Factors
  • Time Factors


  • Antipsychotic Agents