From the Guidelines
Dopamine-depleting parkinsonism is primarily caused by medications that block dopamine receptors, such as antipsychotics, antiemetics, and reserpine, as well as conditions like Parkinson's disease, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration, which are characterized by the degeneration of dopaminergic neurons in the brain. The most common medications causing dopamine-depleting parkinsonism include antipsychotics like haloperidol, risperidone, and chlorpromazine, which block dopamine receptors, as well as antiemetics such as metoclopramide and prochlorperazine, and reserpine and tetrabenazine which deplete presynaptic dopamine 1. These medications can cause tremors, rigidity, bradykinesia, and postural instability, similar to Parkinson's disease.
Causes of Dopamine-Depleting Parkinsonism
- Medications:
- Antipsychotics: haloperidol, risperidone, chlorpromazine
- Antiemetics: metoclopramide, prochlorperazine
- Reserpine and tetrabenazine: deplete presynaptic dopamine
- Neurodegenerative diseases:
- Parkinson's disease
- Progressive supranuclear palsy
- Multiple system atrophy
- Corticobasal degeneration
The symptoms typically develop within days to months of starting the medication and often improve when the offending drug is discontinued, though recovery may take weeks to months. In some cases, particularly with long-term antipsychotic use, symptoms may persist indefinitely as tardive parkinsonism. Management primarily involves discontinuing the causative medication when possible and substituting with alternatives less likely to cause parkinsonism. For antipsychotics, consider atypical options like quetiapine or clozapine. If symptoms persist or the medication cannot be stopped, anticholinergics like trihexyphenidyl or levodopa may provide symptomatic relief, though their effectiveness is often limited compared to their use in idiopathic Parkinson's disease 1.
From the FDA Drug Label
Current evidence indicates that symptoms of Parkinson’s disease are related to depletion of dopamine in the corpus striatum. The causes of dopamine-depleting parkinsonism are related to depletion of dopamine in the corpus striatum 2.
- The exact causes of this depletion are not specified in the drug label.
- However, it is known that Parkinson’s disease is a progressive, neurodegenerative disorder that affects the mobility and control of the skeletal muscular system, and is characterized by resting tremor, rigidity, and bradykinetic movements.
From the Research
Causes of Dopamine-Depleting Parkinsonism
The causes of dopamine-depleting parkinsonism are complex and multifaceted. Some of the possible mechanisms behind the depletion of dopamine in Parkinson's disease patients include:
- Alpha-synuclein abnormalities 3
- Mitochondrial dysfunction 3
- 3,4-dihydroxyphenylacetaldehyde (DOPAL) toxicity 3
- Genetic and environmental factors 3
- Loss of dopaminergic neurons, leading to a reduction in dopamine levels 3
Dopamine Deficiency in Parkinson's Disease
Dopamine deficiency is a core feature of the pathology of Parkinson's disease (PD) 4. The resulting dopamine deficiency is the cause of the typical motor features of Parkinson's disease, including bradykinesia, rigidity, and tremor 5.
Therapeutic Options for Dopamine-Depleting Parkinsonism
Current therapies for dopamine-depleting parkinsonism include: