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Background: Antipsychotics with dopamine (D2) receptor antagonism can be effective for emesis in cancer patients. Extrapyramidal symptoms (EPS) induced by typical antipsychotics can be exacerbated by other D2 receptor antagonists. We describe a case of persistent EPS induced by long‐term, intermittent administration of low‐dose olanzapine along with metoclopramide for emesis. Case Presentation: A 59‐year‐old pancreatic cancer patient underwent chemotherapy for 7 months. He was referred to the psychiatry department because of restlessness and insomnia. Although he did not have obvious depressive symptoms, he was anxious about the cancer treatment. For chemotherapy‐induced nausea, he had been prescribed 5 mg of olanzapine intermittently for 7 months. He had last used the drug 9 days before presenting it to us. Additionally, he received metoclopramide and palonosetron as antiemetics. We considered akathisia and cancer‐related anxiety/agitation as possible causes of restlessness and insomnia, and prescribed clonazepam. However, his symptoms worsened, resulting in hospitalization. We reconsidered his symptoms as cancer‐related anxiety/agitation and prescribed quetiapine. Although it was effective, he had tremors and was assessed by a neurologist. Considering the clinical manifestations of rigidity, postural reflex disorder, and a mask‐like face, we suspected drug‐induced parkinsonism and replaced quetiapine with biperiden on the next day, leading to his discharge after 2 weeks. He did not have symptom recurrence even after discontinuation of biperiden. Conclusions: Long‐term, intermittent administration of low‐dose antipsychotics with other antiemetics having D2 receptor antagonism can cause prolonged EPS. Especially in cancer patients, who often require polypharmacy, clinicians should consider exacerbated adverse effects due to drug interactions. [ABSTRACT FROM AUTHOR]

Background: Patients with older age and female sex are known to have increased risk of developing drug‐induced parkinsonism (DIP). Aim: Basic prescription patterns of drugs associated with a risk of causing DIP remain unclear, which we assessed in this study. Methods: Using the publicly distributed data "NDB Open Data Japan," the summary statistics of Japanese nationwide health claims, we calculated the disproportionality in prescriptions among men and women of different age groups to whom tablets/capsules were prescribed at the outpatient clinic from 2014 to 2017. Based on the 2‐by‐2 contingency table, we derived the odds ratio (OR) to identify which drug is more frequently prescribed to elderly (≥65 y/o) women than to men. Results: Among the calculated ORs of 18 generic DIP‐related drugs we investigated, sulpiride had the highest OR (3.85), followed by tiapride (OR = 2.47), olanzapine (OR = 2.43), and risperidone (OR = 2.27). Among all the drug products included in the database, sulpiride again showed a significantly high OR, which was higher than the 95th percentile of ORs of all 3604 products examined. Conclusion: Our results showed that the distribution of sulpiride prescriptions is biased toward older females, who are more susceptible to develop DIP than males. Assuming the limited indication of sulpiride as the primary treatment option for depression or schizophrenia, a future study on why and how sulpiride is prescribed to the elderly female patients might aid in changing the prescription strategy of sulpiride, thereby possibly reducing the overall incidence of DIP in Japan. [ABSTRACT FROM AUTHOR]

Aims: We conducted a cohort study utilizing a nationwide health insurance database to assess the European Medicines Agency's restrictions on using metoclopramide and its association with the risk of parkinsonism. Methods: New oral metoclopramide users aged ≥20 years, and age‐ and gender‐matched non‐users were recruited between 2001 and 2011. Users were divided into high‐exposure (dose >30 mg day–1 and/or duration >5 days) and standard‐exposure (dose ≤30 mg day–1 and duration ≤5 days) groups. The adjusted hazard ratio (aHR) with 95% confidence interval (CI) estimated the risk of parkinsonism. Results: During a 1‐year period, 122 of 218 931 (0.06%) users of metoclopramide vs. 56 of 218 931 (0.03%) non‐users developed parkinsonism (P < 0.001). Among the 122 cases of parkinsonism in users, 64 (0.04%) were from 168 566 standard‐exposure users and 58 (0.12%) from 50 365 high‐exposure users. Compared with non‐users, the risk of parkinsonism was higher in users (aHR 2.16; 95% CI 1.54, 3.02), including standard‐exposure (aHR 1.73; 95% CI 1.11, 2.70), and high‐exposure (aHR 3.15; 95% CI 1.78, 5.57) users. High‐exposure users had a higher risk of parkinsonism than standard‐exposure users (aHR 1.83; 95% CI 1.28, 2.63). Within the high‐exposure group, 45 233 of 50 365 (89.81%) users and 55 of 58 (94.83%) parkinsonism were from long‐duration exposure; 5 132 of 50 365 (10.19%) users and 3 of 58 (5.17%) parkinsonism were from high‐dose exposure and long‐duration + high‐dose exposure. Conclusions: The risk of parkinsonism in metoclopramide users, although extremely low (0.06%), is 2.16‐fold greater than in non‐users. High‐exposure users have a 1.83‐fold higher risk than standard‐exposure users. As users in high‐exposure group had a higher risk of parkinsonism than in standard‐exposure group, and the majority of users and parkinsonism in high‐exposure group were from long‐duration exposure; thus, physician are advised to avoid prescribing metoclopramide for >5 days, even if the daily dose is ≤30 mg. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies of drug-induced parkinsonism remain limited.Objectives: To investigate the incidence and time trends of drug-induced parkinsonism over 30 years in a geographically defined American population.Methods: We used the medical records-linkage system of the Rochester Epidemiology Project to identify all persons in Olmsted County, Minnesota, who received a screening diagnostic code for parkinsonism from 1976 through 2005. A movement disorders specialist reviewed the complete medical records of each person to confirm the presence of drug-induced parkinsonism associated with dopamine-blocking or dopamine-depleting medications.Results: Among 906 incident cases of parkinsonism from 1976 to 2005, 108 persons had drug-induced parkinsonism (11.9%). The average annual incidence rate of drug-induced parkinsonism was 3.3 per 100,000 person-years, was higher in women, and increased with older age. Drug-induced parkinsonism was the fifth-most common type of parkinsonism overall; however, it was the most common type among persons younger than age 40 years. Typical antipsychotic drugs were the most common class of drugs associated with parkinsonism, whereas atypical antipsychotic drugs were rarely involved. The incidence rate of drug-induced parkinsonism decreased 32.0% per decade (relative risk = 0.68; 95% confidence interval: 0.49-0.94) and 68.6% over the 30 years of the study. The decrease was similar in men (65.2%) and women (69.4%); however, the trend was significant only in women.Conclusions: The incidence of drug-induced parkinsonism increased with older age and was higher in women at all ages. Typical antipsychotic drugs were the most common cause. The incidence of drug-induced parkinsonism decreased over the 30 years of the study because of changes in drug use. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Introduction Response to drug withdrawal in patients with suspected drug-induced parkinsonism ( DIP) is of prognostic and therapeutic importance, but cannot be predicted solely on clinical information. The aim of this study was to validate SN hyperechogenicity ( SN+) assessed by transcranial sonography as a predictor of response to drug withdrawal in this group of patients. Methods Patients were diagnosed according to previously published criteria and prospectively included in the study. All patients were followed until complete recovery of parkinsonian symptoms or at least for 6 months after discontinuation of the offending drug and then diagnosed as DIP or parkinsonism following neuroleptic exposure ( PFNE). Transcranial sonography ( TCS) findings were compared with the clinical diagnosis. Results Sixty patients comprised the group for the final analysis. Sixteen patients were classified as PFNE and 44 as DIP. The area of SN echogenicity was significantly increased in the PFNE group (0.23 cm2; standard deviation [ SD]: 0.04), compared to the DIP group (0.14 cm2; SD, 0.05; one-way analysis of variance; P < 0.001). Normal SN was significantly associated with complete recovery after withdrawal of the parkinsonism-inducing drug ( P < 0.0005). Accuracy of SN+ to distinguish PFNE from DIP was: sensitivity 81.2%; specificity 84.1%; positive predictive value 47.4%; and negative predictive value 96.2%. Conclusions We believe that SN+ assessed with TCS is a valid prognostic marker in the setting of suspected DIP. It is a nonexpensive, feasible technique that can be implemented for proper counseling and guidance of treatment decisions. [ABSTRACT FROM AUTHOR]

Drug-induced parkinsonism is caused by an offending drug and should resolve after the causative agent has been withdrawn. However, in a number of patients, symptoms persist or may even worsen over time, suggesting the development of concomitant Parkinson's disease. The prevalence estimates of Parkinson's disease after neuroleptic exposure are unexpectedly high, suggesting a causal relationship. We critically review available literature in this regard, and some pathophysiological hypotheses that might explain such a relationship are suggested. Some patients may have an undetermined genetic susceptibility to parkinsonism. We speculate that the possible neurotoxic effect of neuroleptics exerted on a susceptible dopaminergic system would lead over the long-term to a self-fostering, progressive process. Knowledge gaps and future perspectives are discussed. © 2015 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background and purpose Differentiating idiopathic Parkinson's disease from secondary parkinsonian syndromes is crucial since their management and prognosis differ considerably. Functional imaging of the dopaminergic pathway by means of [¹²³I] FP- CIT SPECT (Da TSCAN) might be useful in this regard, but its role is still controversial. The accuracy of Da TSCAN in the differential diagnosis between Parkinson's disease and vascular or drug-induced parkinsonism was therefore systematically reviewed. Methods MEDLINE and CENTRAL were searched for studies aiming to determine accuracy measures (sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratios) of Da TSCAN in differentiating between Parkinson's disease and vascular or drug-induced parkinsonism. Results Five studies were included. Pooled accuracy measures in differentiating between Parkinson's disease and vascular or drug-induced parkinsonism were relatively high, with sensitivity and specificity values above 85% and 80%, respectively. Conclusions Da TSCAN might accurately differentiate between early Parkinson's disease and secondary parkinsonian conditions, namely vascular or drug-induced, in patients with clinically unclear parkinsonism. However, all the studies reviewed here show several methodological limits, which prevent definitive conclusions on the role of Da TSCAN being drawn in this context. Further studies are needed to confirm our results and definitely evaluate the utility of Da TSCAN in differentiating between Parkinson's disease and vascular or drug-induced parkinsonism. [ABSTRACT FROM AUTHOR]

Background and purpose Drug-induced parkinsonism usually resolves after discontinuation of the causative agent. However, it persists in some patients, who actually have subclinical neurodegenerative parkinsonism. Identification of this condition is important because these patients could benefit from therapeutic measures. The objective of this study was to prove whether transcranial sonography, a technique used in the diagnosis of neurodegenerative parkinsonism, can be used for the said identification. Methods In this prospective study, patients with drug-induced parkinsonism were followed for at least 6 months after discontinuation of the causative drug and performance of blinded transcranial sonography. Patients were categorized as having iatrogenic parkinsonism if the clinical presentation had resolved or subclinical drug-exacerbated parkinsonism if it persisted. Once the patient was classified into one of the two groups, an expert assessed the transcranial sonography findings and their agreement with the clinical diagnosis. Results Twenty patients composed the group for analysis of results. Assessing hyperechogenicity in the substantia nigra >20 mm2 and/or hyperechogenic lentiform nucleus, differences were detected between the iatrogenic parkinsonism and the subclinical drug-exacerbated parkinsonism groups, although they did not reach statistical significance (Fisher's exact test 0.09). Joint assessment of sonographic alterations in both structures had a negative predictive value of 85.7% for diagnosis of drug-induced parkinsonism, with a negative likelihood ratio of 0.3. Conclusions Although in our study statistically significant differences were not found between the transcranial sonography characteristics of subclinical drug-exacerbated parkinsonism and iatrogenic parkinsonism patients, we believe that transcranial sonography is a valid technique for diagnosis of drug-induced parkinsonism. [ABSTRACT FROM AUTHOR]

Objective The purpose of the present study was to examine the relationship between drug-induced parkinsonism (DIP) and subjective non-motor cognitive impairments in schizophrenia by performing comprehensive assessments of extrapyramidal side effects (EPS) and the subjective cognitive-perceptual functioning. Methods Ninety-one outpatients with schizophrenia were evaluated for DIP and other EPS. Subjective cognitive-perceptual dysfunction was comprehensively assessed using the Frankfurt Complaint Questionnaire (FCQ). To examine the association between DIP and non-motor cognitive-perceptual dysfunction, Pearson's partial correlation analysis was performed between the FCQ scores and the severity of DIP, controlling for relevant variables. Results The analysis revealed that the severity of DIP had a significant correlation with the total FCQ score (p < 0.05). In phenomenological subscales, the severity of DIP showed significant correlations with “deterioration of discrimination,” “psychomotor disorder,” “perceptual disorder,” “cognitive floating,” and “automatic behavior disorder” (p < 0.05). Conclusions The results of our study suggest that DIP is significantly associated with a wide range of subjective non-motor cognitive impairments. Clinicians should be careful of the appearance of DIP and the associated non-motor cognitive-perceptual symptoms, which may cause considerable distress and reduce the quality of life in an already vulnerable group of patients. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]