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Table of Contents    
COMMENTARY
Year : 2021  |  Volume : 69  |  Issue : 2  |  Page : 437-438

Drug-Induced Parkinsonism


1 Department of Neurosurgery, AIIMS, New Delhi, India
2 Department of Neurology, AIIMS, New Delhi, India

Date of Submission16-Apr-2020
Date of Decision04-May-2020
Date of Acceptance10-Jul-2020
Date of Web Publication24-Apr-2021

Correspondence Address:
Kanwaljeet Garg
Department of Neurosurgery, AIIMS, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.314567

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How to cite this article:
Garg K, Rajan R, Singh M. Drug-Induced Parkinsonism. Neurol India 2021;69:437-8

How to cite this URL:
Garg K, Rajan R, Singh M. Drug-Induced Parkinsonism. Neurol India [serial online] 2021 [cited 2021 May 16];69:437-8. Available from: https://www.neurologyindia.com/text.asp?2021/69/2/437/314567




 Parkinsonism More Details refers to a group of neurological disorders that share similar clinical symptoms. Cardinal clinical features of parkinsonism are bradykinesia along with rest tremor and/or rigidity. The most common cause of parkinsonism is idiopathic Parkinson's disease (PD).[1] Other disorders which may present with parkinsonism include secondary parkinsonism (drug-induced, vascular, infection-induced, tumor, and metabolic), parkinsonism plus syndromes or atypical parkinsonism (progressive supranuclear palsy, corticobasal syndrome, multiple system atrophy and dementia with Lewy bodies), and hereditary neurodegenerative disorders (spinocerebellar ataxia, Wilson's disease, neurodegeneration with brain iron accumulation, juvenile-onset Huntington's disease, and fragile-X tremor/ataxia syndrome).[1] It is important to differentiate PD from the other disorders, especially the atypical parkinsonian syndromes, as the course of the disease is more rapid in the latter and improvement with the standard dopaminergic therapy is not complete and only short-lasting.[2]

Drug-induced movement disorders include parkinsonism, akathisia, tardive dyskinesia, tardive dystonia, myoclonus, and tremor.[3],[4],[5],[6] Drug-induced parkinsonism (DIP) is the commonest amongst these. DIP is second only to PD as the cause of parkinsonism.[7] The drugs which cause DIP usually interfere with the postsynaptic dopamine receptors, particularly D2 receptors. Other drugs may impair dopamine synthesis presynaptically. Commonest drugs to cause DIP are typical antipsychotics (chlorpromazine, prochlorperazine, etc). Though atypical antipsychotics (olanzapine, risperidone) have lesser potential to cause drug-induced movement disorders, they may also result in DIP.[6] Other drugs that can frequently cause DIP are gastrointestinal motility drugs (metoclopramide, levosulpiride, and clebopride), calcium channel blockers (flunarizine and cinnarizine), and dopamine depleters (tetrabenazine and deutetrabenazine).[6],[8],[9],[10] A certain group of drugs that can occasionally cause DIP are mood stabilizers like lithium, antidepressants like selective serotonin receptor uptake inhibitors, antiemetics like domperidone, and antiepileptic drugs like phenytoin and valproate.[6]

Pregabalin is structurally related to gabapentin but does not have any interaction with gamma aminobutyric acid (GABA) receptors. Rather it acts by blocking the L-type, voltage-dependent, calcium-channel which regulates the secretion of neurotransmitters in the synaptic cleft from the presynaptic neuron.[11] It is commonly used in the treatment of neuropathic pain and some forms of seizures. There are few reports of pregabalin causing DIP.[12] However, the exact mechanism of DIP caused by pregabalin needs to be established yet.

Clinical features of DIP include bilateral symmetric parkinsonism, and more severe rigidity and bradykinesia than in patients with PD.[13] Rigidity was found to be the commonest symptom in one series.[14] Although the classical resting tremor is often absent, chin tremor may be seen in DIP. These features are not fully diagnostic of DIP as many patients can have asymmetric symptoms and resting tremors like the patients of PD.[6] Hence, making correct diagnosis just based on clinical findings can be difficult in the presence of overlapping symptoms. The diagnostic clinical criteria for DIP are the presence of typical clinical symptoms of parkinsonism with onset after starting an offending drug, and in the absence of a history of parkinsonism before.[6] Old age, female gender, and genetic factors are the known risk factors for DIP.[13],[15],[16]

The symptom onset in DIP may be delayed by weeks after the offending drug is started, and 50–75% of patients usually become symptomatic within 1 month of starting the offending drug.[9] Since the clinical manifestation of DIP and PD is the same, many patients with DIP get labeled as PD and receive prolonged treatment.[3],[17] The true incidence of DIP is not known because of the same reason. One has to be careful in diagnosing PD and take a detailed history of any medicinal usage which can lead to DIP.

Dopaminergic imaging can be used to differentiate between PD and DIP.[18] It targets the dopamine active transporter (DAT), which is a transporter protein on the presynaptic dopaminergic nerve terminal and controls dopamine reuptake after it has interacted with the postsynaptic receptor.[19] DAT density in the striatum is decreased in PD (even in patients with mild symptoms) but normal in DIP as it results from blockade of postsynaptic dopamine receptors (especially D2 receptors). It can be targeted by single-photon emission computed tomography (SPECT) and positron emission tomography (PET) scans using several DAT ligands. SPECT has reasonable sensitivity and specificity (>80%) in differentiating DIP from PD.[20],[21] PET imaging has better sensitivity and spatial resolution than SPECT but is more costly.[18]

The first step in the management of DIP after the diagnosis has been made is to stop the offending drug. If the offending drug cannot be stopped as in patients with psychosis, the offending drug can be replaced with a drug that is less likely to cause DIP like atypical antipshycotics (clozapine, quetiapine).[2],[6] Anticholinergics are the drug of choice in significantly symptomatic patients; however, their definitive role is doubtful and should be judiciously weighed against the risks of aggravating psychosis.[2] DIP usually responds to the withdrawal of the offending drug in a few weeks to months. However, 10–50% of patients can have persistent symptoms.[2] Four patterns of course have been described by Shin et al.[2] There can be complete recovery from DIP with no recurrence of symptoms, or there can be few persistent symptoms that do not progress further, or symptoms can persist which eventually worsen, or complete recovery but later recurrence. They classified the first category as “pure DIP.”[2] There are chances of progression of the last two categories to PD and these patients may represent the preclinical stage of PD in whom the symptoms of PD are unmasked as a result of the drug-induced dopaminergic blockade.[2],[10]



 
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