Trends in the Prevalence of Drug-Induced Parkinsonism in Korea

PURPOSE: Discontinuation of offending drugs can prevent drug-induced parkinsonism (DIP) before it occurs and reverse or cure it afterwards. The aim of this study was to investigate the prevalence of DIP and the utilization of offending drugs through an analysis of representative nationwide claims data. MATERIALS AND METHODS: We selected DIP patients of ages ranging from 40 to 100 years old with the G21.1 code from the Korean National Service Health Insurance Claims database from 2009 to 2015. The annual standardized prevalence of DIP was explored from 2009 to 2015. Trends were estimated using the compound annual growth rate (CAGR) and the Cochran-Armitage test for DIP over the course of 6 years. Additionally, the utilization of offending drugs was analyzed. RESULTS: The annual prevalence of DIP was 4.09 per 100000 people in 2009 and 7.02 in 2015 (CAGR: 9.42%, p<0.001). Levosulpiride use before and after DIP diagnosis showed a clear trend for decreasing utilization (CAGR: −5.4%, −4.3% respectively), whereas the CAGR for itopride and metoclopramide increased by 12.7% and 6.4%, respectively. In 2015, approximately 46.6% (858/1840 persons) of DIP patients were prescribed offending drugs after DIP diagnosis. The most commonly prescribed causative drug after DIP diagnosis was levosulpiride. CONCLUSION: The prevalence of DIP has increased. To prevent or decrease DIP, we suggest that physicians reduce prescriptions of benzamide derivatives that have been most commonly used, and that attempts be made to find other alternative drugs. Additionally, the need for continuing education about offending drugs should be emphasized.

Cardiovascular Autonomic Dysfunction in Patients with Drug-Induced Parkinsonism

BACKGROUND AND PURPOSE: Recent studies have shown that several nonmotor symptoms differ between Parkinson's disease (PD) and drug-induced parkinsonism (DIP). However, there have been no reports on cardiovascular autonomic function in DIP, and so this study investigated whether cardiovascular autonomic function differs between PD and DIP patients. METHODS: This study consecutively enrolled 20 DIP patients, 99 drug-naïve PD patients, and 25 age-matched healthy controls who underwent head-up tilt-table testing and 24-h ambulatory blood pressure monitoring. RESULTS: Orthostatic hypotension was more frequent in patients with PD or DIP than in healthy controls. In DIP, orthostatic hypotension was associated with the underlying psychiatric diseases and neuroleptics use, whereas prokinetics were not related to orthostatic hypotension. The supine blood pressure, nighttime blood pressure, and nocturnal blood pressure dipping did not differ significantly between the DIP and control groups. Supine hypertension and nocturnal hypertension were more frequent in PD patients than in controls. CONCLUSIONS: The included DIP patients frequently exhibited orthostatic hypotension that was associated with the underlying diseases as well as the nature of and exposure time to the offending drugs. Clinicians should individualize the manifestations of DIP according to underlying diseases as well as the action mechanism of and exposure time to each offending drug.

Clinical Features Indicating Nigrostriatal Dopaminergic Degeneration in Drug-Induced Parkinsonism

OBJECTIVE: Patients with drug-induced parkinsonism (DIP) may have nigrostriatal dopaminergic degeneration. We studied the clinical features that may indicate nigrostriatal dopaminergic degeneration in patients with DIP. METHODS: Forty-one DIP patients were classified into normal and abnormal [¹⁸F] FP-CIT scan groups. Differences in 32 clinical features and drug withdrawal effects were studied. RESULTS: Twenty-eight patients had normal (Group I) and 13 patients had abnormal (Group II) scans. Eight patients of Group I, but none of Group II, had taken calcium channel blockers (p = 0.040). Three patients of Group I and six of Group II had hyposmia (p = 0.018). After drug withdrawal, Group I showed greater improvement in Unified Parkinson's Disease Rating Scale total motor scores and subscores for bradykinesia and tremors than Group II. Only hyposmia was an independent factor associated with abnormal scans, but it had suboptimal sensitivity. CONCLUSION: None of the clinical features were practical indicators of nigrostriatal dopaminergic degeneration in patients with DIP.

Clebopride-Induced Parkinsonism

No abstract available.

Cognitive Dysfunction in Drug-induced Parkinsonism Caused by Prokinetics and Antiemetics

The use of prokinetics/antiemetics is one of the leading causes of drug-induced parkinsonism (DIP) observed in neurology clinics. Cognitive dysfunction in DIP has recently been recognized, but pathologies related with cognitive dysfunction is unknown. Among our retrospective cohort of 385 consecutive parkinsonian patients enrolled in our parkinsonism registry, 14 patients were identified who satisfied our inclusion criteria: parkinsonism caused by prokinetics/antiemetics, existing T1-weighted 3D volumetric MR images, and normal [18F]-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane PET scan images. For the comparison of volumetric MR data, 30 age- and sex-matched healthy individuals were included in this study. Among 14 patients with DIP, 4 patients were diagnosed with dementia, and all other patients had mild cognitive impairment (MCI). Comparisons of MR volumetric data between DIP patients with MCI and controls show that cortical gray matter volumes are reduced bilaterally in DIP (P=0.041) without changes in either total white matter volume or total intracranial volume. Among subcortical structures, the volume of the right hippocampus is reduced in DIP patients compared with controls (P=0.011, uncorrected). In DIP, cortical thickness is reduced in the bilateral lingual (P=0.002), right fusiform (P=0.032) and part of the left lateral occipital gyri (P=0.007). Our results suggests that cognitive dysfunction in DIP caused by prokinetics/antiemetics is common. Structural changes in the brain by 3D MRI may be associated with cognitive decline in DIP.

Pharmacotherapy in patients with drug-induced parkinsonism: A case series.

Drug-induced Parkinsonism develops in a number of patients with schizophrenia or schizo-affective disorders. Conventionally, anti-parkinsonism drugs, such as levodopa and dopamine agonists have been avoided due to their potential to result in an increase in psychotic symptoms, hallucinations and behavioral disturbance. We present ten cases series of drug-induced Parkinsonism in whom a trial of antiparkinsonism medications administered commenced with good effect. In particular, there was no deterioration in psychotic symptoms. A number of cases had asymmetrical signs, suggesting that these patients had a component of idiopathic Parkinson’s disease in addition to long standing drug-induced Parkinsonism. The diagnosis of idiopathic Parkinson’s disease on clinical grounds is often difficult in patients who have been on or are currently on an anti-psychotic drug. A trial of levodopa or a dopamine agonist is worth considering, albeit cautiously. In our series of cases a relapse or exacerbation of psychotic symptoms did not occur after commencing levodopa and dopamine agonists.

Clinical Implications of Cardiac-MIBG SPECT in the Differentiation of Parkinsonian Syndromes

BACKGROUND AND PURPOSE: 123I cardiac meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been used to estimate myocardial sympathetic nerve function. We investigate whether cardiac-MIBG SPECT is clinically applicable in the differentiation of Parkinson's disease (PD) from parkinsonian syndromes. METHODS: Cardiac-MIBG scintigraphy was performed in 27 controls, in 40 patients with PD and in 52 patients with other parkinsonian syndromes comprising 23 with multiple system atrophy (MSA), 26 with drug-induced parkinsonism (DIP), and 3 with corticobasal degeneration (CBD). The heart to mediastinum (H/M) uptake ratio was calculated for each subjects. Patients who either had medical conditions that confused the MIBG SPECT results or who took medications that interfere with MIBG accumulation were excluded from the study. RESULTS: Both early and delayed H/M ratios were in patients with PD significantly lower than in controls (early, 1.34+/-0.15 vs 1.79+/-0.19; delayed, 1.29+/-0.15 vs 2.06+/-0.29, p<0.001). In patients with PD, both early and delayed H/M ratios were significantly lower than those in patients with MSA (early, 1.68+/-0.23; delayed, 1.80+/-0.34, p<0.001), DIP (early, 1.83+/-0.24; delayed, 2.07+/-0.4, p<0.001), or CBD (early, 1.85+/-0.01; delayed, 1.99+/-0.19, p<0.001). Two patients with DIP, who were within the range of patients with PD, showed clinically similar courses of PD. CONCLUSIONS: This study demonstrates that cardiac-MIBG is a clinically powerful tools to differentiate PD from other parkinsonian syndromes.

Levosulpiride-induced Parkinsonim

The present report discusses four cases of chronic renal failure, which developed symptoms of parkinsonism in response to levosulpiride. The temporal relationship between levosulpiride discontinuation and the disappearance of parkinsonism suggests a causal link. In addition, decreased striatal dopamine transporter bindings assessed by [I-123] IPT SPECT were observed in two patients suggesting that a dopamine blocking agent causes the dysfunction of nigrostriatal dopaminergic neurons and that such injury may be involved in the pathogenesis of drug-induced parkinsonism.