Antipsychotic Drug-Induced Damage in the Basal Ganglia as a Cause of Parkinsonism: A Review of the Literature
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Abstract
Parkinsonism refers to a set of conditions featuring motor symptoms such as slowness, tremor, and rigidity that are most commonly observed in older patients. Forms of Parkinsonism, including Parkinson’s disease (PD) and drug-induced Parkinsonism (DIP), can be difficult to distinguish clinically and are associated with dysfunction in a subcortical brain region known as the basal ganglia, a group of structures which include the striatum. The basal ganglia receive dopaminergic projections from the substantia nigra pars compacta (SNc), and interfacing with the extrapyramidal system, these brain regions are critical in the regulation of involuntary and voluntary motor movements. Input from premotor areas and the cerebral cortex relay signals to the caudate and putamen forming the indirect and direct pathways. Both of which have competing, yet balanced, effects on movement. Reductions in either dopamine signaling or numbers of projecting neurons in these pathways leads to Parkinsonism. DIP can be initiated by dopamine receptor blocking agents, including first- (FGA) and second-generation (SGA) antipsychotic drugs, which block D2 dopaminergic receptors. FGAs and SGAs primarily differ in D2 receptor affinity, with FGAs generally being higher. FGAs are more likely to cause DIP than SGAs, but despite the difference in receptor affinities, they are both capable of inducing motor deficits at varying concentrations. Unlike in PD, motor deficits in DIP may be alleviated upon withdrawal of the offending drug, but in some cases, patients continue to experience Parkinsonism symptoms for years. It is not known whether these more permanent forms of DIP may result from damage in the basal ganglia caused by FGAs and SGAs. Based on a review of the literature, evidence that prolonged exposure to, or high concentrations of these drugs, promotes neuronal dysfunction and induces permanent PD in patients is explored.
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Drug-Induced Parkinsonism, Parkinson's Disease, Basal Ganglia, Antipsychotic Drugs, Dopamine