J Clin Neurol.  2012 Mar;8(1):15-21. 10.3988/jcn.2012.8.1.15.

Drug-Induced Parkinsonism

• Shin HW
• Chung SJ

• KMID: 2287613
• DOI: http://doi.org/10.3988/jcn.2012.8.1.15

Abstract

Drug-induced parkinsonism (DIP) is the second-most-common etiology of parkinsonism in the elderly after Parkinson's disease (PD). Many patients with DIP may be misdiagnosed with PD because the clinical features of these two conditions are indistinguishable. Moreover, neurological deficits in patients with DIP may be severe enough to affect daily activities and may persist for long periods of time after the cessation of drug taking. In addition to typical antipsychotics, DIP may be caused by gastrointestinal prokinetics, calcium channel blockers, atypical antipsychotics, and antiepileptic drugs. The clinical manifestations of DIP are classically described as bilateral and symmetric parkinsonism without tremor at rest. However, about half of DIP patients show asymmetrical parkinsonism and tremor at rest, making it difficult to differentiate DIP from PD. The pathophysiology of DIP is related to drug-induced changes in the basal ganglia motor circuit secondary to dopaminergic receptor blockade. Since these effects are limited to postsynaptic dopaminergic receptors, it is expected that presynaptic dopaminergic neurons in the striatum will be intact. Dopamine transporter (DAT) imaging is useful for diagnosing presynaptic parkinsonism. DAT uptake in the striatum is significantly decreased even in the early stage of PD, and this characteristic may help in differentiating PD from DIP. DIP may have a significant and longstanding effect on patients' daily lives, and so physicians should be cautious when prescribing dopaminergic receptor blockers and should monitor patients' neurological signs, especially for parkinsonism and other movement disorders.

Keyword

Parkinsonism; dopamine receptor blocking agents; clinical manifestations; dopamine transporter imaging; treatment

MeSH Terms

Aged
Anticonvulsants
Antipsychotic Agents
Basal Ganglia
Calcium Channel Blockers
Dopamine Plasma Membrane Transport Proteins
Dopaminergic Neurons
Humans
Movement Disorders
Organothiophosphorus Compounds
Parkinson Disease
Parkinsonian Disorders
Tremor
Anticonvulsants
Antipsychotic Agents
Calcium Channel Blockers
Dopamine Plasma Membrane Transport Proteins
Organothiophosphorus Compounds

Figure

• 

  Fig. 1 Changes in basal ganglia-thalamocortical motor loop due to blockade of D2 receptors by DRBAs. The blockage of D2 receptors by DRBAs in the striatum leads to disinhibition of GABA- and encephalin-containing striatal neurons at the origin of the indirect pathway, followed by a disinhibition of the subthalamic nucleus. This leads to increased GABAergic inhibition of the thalamocortical projection by facilitation of the inhibitory projection from the GPi/SNr (A). Chronic D2 receptor blockade also induces changes in the direct pathways of the basal ganglia-motor loop to cause orolingual dyskinesia (B). DA: dopamine, DRBAs: dopamine receptor blocking agents, GABA: gamma-aminobutyrik acid, GPe: globus pallidus pars externa, GPi: globus pallidus pars internal, SNc: substantia nigra pars compacta, SNr: substantia nigra pars reticulata, STN: subthalamic nucleus, TD: tardive dyskinesia.

• 

  Fig. 2 123I-FP-CIT PET imaging in two DIP patients. DAT uptake was normal and symmetric in the bilateral striatum in a pure DIP patient (A), whereas it decreased severely in the right striatum in a patient who was diagnosed with PD unmasked by DRBAs (B). DAT: dopamine transpoter, DIP: drug-induced parkinsonism, DRBA: dopamine receptor blocking agents, PD: Parkinson's disease.

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