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• We used resting-state EEG to investigate neural markers characterizing drug-induced parkinsonism and Parkinson's disease. • Drug-induced parkinsonism patients exhibited higher theta band power than Parkinson's disease patients and controls. • Drug-induced parkinsonism patients showed increased theta and delta band coherence compared with Parkinson's disease. Drug-induced parkinsonism (DIP) ranks second to Parkinson's disease (PD) in causing parkinsonism. Despite sharing similar symptoms, DIP results from exposure to specific medications or substances, underscoring the need for accurate diagnosis. Here, we used resting-state electroencephalography (rsEEG) to investigate neural markers characterizing DIP and PD. We conducted a retrospective analysis of rsEEG recordings from 18 DIP patients, 43 de novo PD patients, and 12 healthy controls (HC). After exclusions, data from 15 DIP, 41 PD, and 12 HC participants were analyzed. EEG spectral power and inter-channel coherence were compared across the groups. Our results demonstrated significant differences in rsEEG patterns among DIP, PD, and HC groups. DIP patients exhibited increased theta band power compared with PD patients and HC. Moreover, DIP patients showed higher delta band coherence compared with PD patients. The current study highlights the differences in EEG spectral power and inter-channel coherence between DIP and PD patients. Our results suggest that rsEEG holds promise as a valuable tool for capturing differential characteristics between DIP and PD patients. [ABSTRACT FROM AUTHOR]

Abstract Pain is common in Parkinson’s disease and frequently observed in other diseases involving parkinsonism. Abnormal scaling function in PD has been reportedly associated with pain, but the role of this function in pain in other parkinsonism-related diseases remains unknown. We screened 127 patients with multiple system atrophy (MSA, n = 24), progressive supranuclear palsy (PSP, n = 15), drug-induced parkinsonism (DIP, n = 56), or vascular parkinsonism (VP, n = 32). After screening, 79 patients with parkinsonism (23 MSA, 10 PSP, 28 DIP, and 18 VP patients) were included in the study. We divided the patients of each group into two groups (with or without pain).The percentages of patients in those groups with pain were 73.9%, 50.0%, 67.9%, and 66.7%, respectively. There was no difference in mean SDT between patients with and without pain in any disease (all p ≥ 0.052). The number of patients showing unmeasurable SDT did not differ between those with and without pain in any disease (all p ≥ 0.316). Our study found no evidence of a role of scaling function in pain development in parkinsonian disorders such as atypical parkinsonism, DIP, and VP.

Background: The side effect of Parkinsonism due to chlorpromazine emerged three years after its approval for public use, leading to the understanding that conventional anti-psychotics could induce various Extrapyramidal Symptoms (EPS). Drug-Induced Parkinsonism (DIP) generally surfaces within days to weeks, but rare instances present delayed onset. Case Presentation: We present a case involving a 28-year-old male exhibiting drug-induced Parkinsonism triggered by a chlorpromazine-based regimen, three months following its initiation. Subsequent symptom relief was observed post-discontinuation. [ABSTRACT FROM AUTHOR]

Introduction: This research aimed to investigate the pathophysiological mechanism of how drug-induced parkinsonism (DIP) affects the integrity of the white matter (WM) fiber microstructure as measured by magnetic resonance diffusion tensor image (DTI) fractional anisotropy (FA) and mean diffusivity (MD). Methods: We recruited 17 participants diagnosed with DIP, 20 Parkinson’s disease (PD) patients, and 16 normal controls (NCs) with a similar age, gender, and years of education. Subsequently, all participants underwent DTI magnetic resonance imaging scanning. To analyze the data, we utilized the software packages Functional MRI of the Brain Centre (FMRIB) Diffusion Toolbox (FDT), developed by the FMRIB laboratory at Oxford University, and tract-based spatial statistics (TBSS). Results: The Argentina Hyposmia Rating Scale (AHRS) scores of patients in DIP group were markedly higher than those in PD patients group. Compared with the NC group, the FA values in the genu and body of the corpus callosum (CC), anterior limb of the right internal capsule, bilateral anterior corona radiata, bilateral superior corona radiata, right external capsule, and right superior fronto-occipital fasciculus (could be a part of the anterior internal capsule) were significantly decreased in the DIP group; however, no significant cluster was found in MD. Conclusions: The present study provides novel insights into the alterations in WM microstructure among DIP patients, suggesting that these methodologies have the potential to aid in the early diagnosis and treatment of DIP.

Introduction and purpose: The parkinsonian syndrome is a component of Parkinson's disease. A thorough neurological examination can detect symptoms belonging to the parkinsonian syndrome. Diagnosis using the Queen Square Brain Bank criteria is based on the presence of bradykinesia along with one additional symptom in the patient. These include muscle rigidity or resting tremors at a frequency of 4-6 Hz, or postural disturbances that cannot be explained by visual, vestibular, cerebellar, or deep sensory disorders. The parkinsonian syndrome can occur in idiopathic Parkinson's disease, hereditary disorders, secondary parkinsonism, or be part of an atypical parkinsonian syndrome. The aim of the study was to discuss the diagnostic features and differences in the occurrence of the parkinsonian syndrome as a component of Parkinson's disease, both within the context of other neurological disorders. Materials and method: The foundation of the research was medical articles gathered from the Google Scholar database. The studies were conducted by analyzing keywords such as "parkinsonism," "druginduced parkinsonism," and "vascular parkinsonism". Results: Secondary parkinsonism, or secondary parkinsonism syndrome, can be indicated by clinical features such as: disease onset below the age of 40, abrupt onset, rapid disease progression, symptoms related to medication use, and symptoms associated with the underlying condition. In addition to clinical evaluation, imaging studies are also employed. Conclusions: Various conditions can lead to the development of secondary parkinsonism, including hydrocephalus, brain tumors, encephalitis, cerebral atherosclerosis, traumatic brain injuries, medications, and poisoning. The aforementioned conditions exert different mechanisms of influence on the central nervous system. [ABSTRACT FROM AUTHOR]

Different types of resistance to passive movement, i.e. hypertonia, were described in schizophrenia spectrum disorders (SSD) long before the introduction of antipsychotics. While these have been rediscovered in antipsychotic-naïve patients and their non-affected relatives, the existence of intrinsic hypertonia vs drug-induced parkinsonism (DIP) in treated SSD remains controversial. This integrative review seeks to develop a commonly accepted framework to specify the putative clinical phenomena, highlight conflicting issues and discuss ways to challenge each hypothesis and model through adversarial collaboration. The authors agreed on a common framework inspired from systems neuroscience. Specification of DIP, locomotor paratonia (LMP) and psychomotor paratonia (PMP) identified points of disagreement. Some viewed parkinsonian rigidity to be sufficient for diagnosing DIP, while others viewed DIP as a syndrome that should include bradykinesia. Sensitivity of DIP to anticholinergic drugs and the nature of LPM and PMP were the most debated issues. It was agreed that treated SSD should be investigated first. Clinical features of the phenomena at issue could be confirmed by torque, EMG and joint angle measures that could help in challenging the selectivity of DIP to anticholinergics. LMP was modeled as the release of the reticular formation from the control of the supplementary motor area (SMA), which could be challenged by the tonic vibration reflex or acoustic startle. PMP was modeled as the release of primary motor cortex from the control of the SMA and may be informed by subclinical echopraxia. If these challenges are not met, this would put new constraints on the models and have clinical and therapeutic implications. [ABSTRACT FROM AUTHOR]

In the first half of the 20th century, well before the antipsychotic era, paratonia, Gegenhalten and psychomotor hypertonia were described as new forms of hypertonia intrinsic to particular psychoses and catatonic disorders. A series of astute clinical observations and experiments supported their independence from rigidity seen in Parkinson's disease. After World War II, motor disorders went out of fashion in psychiatry, with drug-induced parkinsonism becoming the prevailing explanation for all involuntary resistance to passive motion. With the 'forgetting' of paratonia and Gegenhalten , parkinsonism became the prevailing reading grid, such that the rediscovery of hypertonia in antipsychotic-naive patients at the turn of the 21st century is currently referred to as "spontaneous parkinsonism", implicitly suggesting intrinsic and drug-induced forms to be the same. Classical descriptive psychopathology gives a more nuanced view in suggesting two non-parkinsonian hypertonias: (i) locomotor hypertonia corresponds to Ernest Dupré's paratonia and Karl Kleist's reactive Gegenhalten ; it is a dys-relaxation phenomenon that often needs to be activated. (ii) Psychomotor hypertonia is experienced as an admixture of assistance and resistance that partially overlaps with Kleist's spontaneous Gegenhalten , but was convincingly isolated by Henri Claude and Henri Baruk thanks to electromyogram recordings; psychomotor hypertonia is underpinned by "anticipatory contractions" of cortical origin, occurrence of which in phase or antiphase with the movement accounted for facilitation or opposition to passive motions. This century-old knowledge is not only of historical interest. Some results have recently been replicated in dementia and as now known to involve specific premotor systems. [ABSTRACT FROM AUTHOR]

Introduction and aim of work: The parkinsonian syndrome is a component of Parkinson's disease. A thorough neurological examination can detect symptoms belonging to the parkinsonian syndrome. Diagnosis using the Queen Square Brain Bank criteria is based on the presence of bradykinesia along with one additional symptom in the patient. These include muscle rigidity or resting tremors at a frequency of 4-6 Hz, or postural disturbances that cannot be explained by visual, vestibular, cerebellar, or deep sensory disorders. The parkinsonian syndrome can occur in idiopathic Parkinson's disease, hereditary disorders, secondary parkinsonism, or be part of an atypical parkinsonian syndrome. The aim of the study was to discuss the diagnostic features and differences in the occurrence of the parkinsonian syndrome as a component of Parkinson's disease, both within the context of other neurological disorders. Materials and methods: The foundation of the research was medical articles gathered from the Google Scholar database. The studies were conducted by analyzing keywords such as "parkinsonism," "drug-induced parkinsonism," and "vascular parkinsonism." Results: Secondary parkinsonism, or secondary parkinsonism syndrome, can be indicated by clinical features such as: disease onset below the age of 40, abrupt onset, rapid disease progression, symptoms related to medication use, and symptoms associated with the underlying condition. In addition to clinical evaluation, imaging studies are also employed. Various conditions can lead to the development of secondary parkinsonism, including hydrocephalus, brain tumors, encephalitis, cerebral atherosclerosis, traumatic brain injuries, medications, and poisoning. The aforementioned conditions exert different mechanisms of influence on the central nervous system.

Background Vietnam-era veterans were exposed to Agent Orange (AO), which is associated with a high prevalence of Parkinson's disease (PD). However, little is known about the development of PD-like symptoms caused by drug-induced parkinsonism (DIP) in such populations. This study aimed to investigate PD incidence and PD risk following exposure to AO or DIP-risk drugs in veterans. Methods A retrospective cohort study was conducted using 12 years (2009–2020) of electronic medical records of the Veterans Health Service Medical Center, the largest Veterans Affairs hospital in South Korea (n  = 37,246; 100% male; age, 65.57 ± 8.12 years). Exposure to AO or DIP-risk drugs, including antipsychotic, prokinetic, anti-epileptic, dopamine-depleting and anti-anginal agents, was assessed in veterans with PD, operationally defined as having a PD diagnosis and one or more prescriptions for PD treatment. The PD risk was calculated using multiple logistic regression analysis adjusted for age and comorbidities. Results The rates of DIP-risk drug use and AO exposure were 37.92% and 62.62%, respectively. The PD incidence from 2010 to 2020 was 3.08%; 1.30% with neither exposure, 1.63% with AO exposure, 4.38% with DIP-risk drug use, and 6.33% with both. Combined exposure to AO and DIP-risk drugs increased the PD risk (adjusted odds ratio = 1.68, 95% confidence interval, 1.36–2.08, P  < 0.001). Conclusions The PD incidence was 1.31 times higher with AO exposure alone and 1.68 times higher with AO exposure and DIP-risk drug use. The results suggest the necessity for careful monitoring and DIP-risk drug prescription in patients with AO exposure. [ABSTRACT FROM AUTHOR]

Matthew Feldman,&ast; Sarah Marmol,&ast; Jason Margolesky Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA&ast;These authors contributed equally to this workCorrespondence: Jason Margolesky, Department of Neurology, University of Miami Miller School of Medicine, 1150 NW 14th St, Miami, FL, 33136, USA, Email jhmargolesky@med.miami.eduAbstract: Parkinsonism refers to the clinical combination of bradykinesia, rigidity, tremor, and postural instability. Parkinsonism is often neurodegenerative, but it can be secondary or iatrogenic, as in drug-induced parkinsonism (DIP), which is the topic of this review. We review the pathophysiology of DIP, differentiate DIP and idiopathic Parkinson’s disease (PD), list culprit medications in the development of DIP, discuss the diagnosis of DIP as well as the motor and nonmotor signs and symptoms that can help with differentiation of DIP and PD, and detail the management of DIP.Keywords: drug-induced parkinsonism, neuroleptic-induced parkinsonism, Parkinson’s disease

This retrospective cohort study assessed treatment changes and prognoses after incident drug-induced parkinsonism (DIP). We used the National Health Insurance Service's National Sample Cohort database in South Korea. We selected patients diagnosed with incident DIP and given prescriptions to take offending drugs (antipsychotics, gastrointestinal (GI) motility drugs, or flunarizine) for a period of time that overlapped with the time of DIP diagnosis during 2004–2013. The proportion of patients experiencing each type of treatment change and prognosis was assessed for 2 years after DIP diagnosis. We identified 272 patients with incident DIP (51.9% of patients were aged ≥ 60 years and 62.5% of them were women). Switching (38.4%) and reinitiation (28.8%) were the most common modifications in GI motility drug users, whereas dose adjustment (39.8%) and switching (23.0%) were common in antipsychotic users. The proportion of persistent users was higher among antipsychotic users (7.1%) than that among GI motility drug users (2.1%). Regarding prognosis, 26.9% of patients experienced DIP recurrence or persistence, the rate being the highest in persistent users and the lowest in patients who discontinued the drug. Among patients with incident DIP diagnoses, the patterns of treatment change and prognosis differed across the types of offending drugs. Over 25% of patients experienced DIP recurrence or persistence, highlighting the need for an effective strategy to prevent DIP. [ABSTRACT FROM AUTHOR]

Abstract 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.

Background: Drug-induced parkinsonism (DIP) is the most prevalent neurological side effect of antipsychotics in the Chinese population. Early prevention, recognition, and treatment of DIP are important for the improvement of treatment outcomes and medication adherence of schizophrenia patients. However, the risk factors of DIP and the impact on the clinical syndromes of schizophrenia remain unknown. Aim: The goal of this study was to explore the risk factors, clinical correlates, and social functions of DIP in Chinese schizophrenia patients. Methods: A cross-sectional analysis of a multicenter, observational, real-world, prospective cohort study of the Chinese schizophrenia population with a baseline assessment was conducted from the year 2012 to 2018. Participants were recruited from four mental health centers in Shanghai and totaled 969 subjects. Sociodemographic data, drug treatment, and clinical variables were compared between the DIP group and the non-DIP group. Variables that correlated with the induction of DIP, and with p≤ 0.1, were included in the binary logistic model for analyzing the risk factors of DIP. First generation antipsychotics (FGA)/second generation antipsychotics (SGA) model and high and low/medium D2 receptor antipsychotics were analyzed respectively to control the bias of colinearity. All risk factors derived from the a forementioned models and clinical variables with p≤ 0.1 were included in the multivariate analysis of clinical correlates and social function of DIP patients. The Positive and Negative Syndrome Scale (PANSS) model and the personal and social performance (PSP) model were analyzed separately to control for co-linearity bias. Results: Age (OR = 1.03, p< 0.001), high D2 receptor antagonist antipsychotic dose (OR = 1.08, p = 0.032), and valproate dose (OR = 1.01, p = 0.001) were the risk factors of DIP. FGA doses were not a significant contributor to the induction of DIP. Psychiatric symptoms, including more severe negative symptoms (OR = 1.09, p< 0.001), lower cognition status (OR = 1.08, p = 0.033), and lower excited symptoms (OR = 0.91, p = 0.002), were significantly correlated with DIP induction. Social dysfunction, including reduction in socially useful activities (OR = 1.27, p = 0.004), lower self-care capabilities (OR = 1.53, p< 0.001), and milder disturbing and aggressive behavior (OR = 0.65, p< 0.001), were significantly correlated with induction of DIP. Valproate dose was significantly correlated with social dysfunction (OR = 1.01, p = 0.001) and psychiatric symptoms (OR = 1.01, p = 0.004) of DIP patients. Age may be a profound factor that affects not only the induction of DIP but also the severity of psychiatric symptoms (OR = 1.02, p< 0.001) and social functions (OR = 1.02, p< 0.001) of schizophrenia patients with DIP. Conclusion: Age, high D2 receptor antagonist antipsychotic dose, and valproate dose are risk factors for DIP, and DIP is significantly correlated with psychiatric symptoms and social performance of Chinese schizophrenia patients. The rational application or discontinuation of valproate is necessary. Old age is related to psychotic symptoms and social adaption in Chinese schizophrenic patients, and early intervention and treatment of DIP can improve the prognosis and social performance of schizophrenia patients. [ABSTRACT FROM AUTHOR]

Introduction: Drug-induced parkinsonism (DIP) is one of the most common iatrogenic movement disorders. It is characterized by tremors, slowness of movement, and shuffling gait with postural instability, clinically indistinguishable from idiopathic Parkinson's disease. Prior exposure to antipsychotic medications or other dopamine receptor blocking agents (DRBAs) is required for the diagnosis., Areas Covered: This article aims to review the epidemiology, pathophysiology, clinical features, ancillary testing, and treatment of DIP. A literature search was undertaken in PubMed from January 2013 to January 2024., Expert Opinion: A clinician's suspicion of DIP must always be present when a patient develops acute to subacute onset of parkinsonism while taking a DRBA. As DIP can be indistinguishable from idiopathic PD, ancillary testing, such as DaTscans and skin biopsy searching for alpha-synuclein deposits, are often required to make a definitive diagnosis. When DIP develops, steps should be taken to discontinue the offending agent or, in the case of antipsychotics, dose reduction or change to an agent with lower risk for DIP, such as quetiapine or clozapine. Prophylactic treatment with anticholinergics is not indicated.

Introduction: This research aimed to investigate the pathophysiological mechanism of how drug-induced parkinsonism (DIP) affects the integrity of the white matter (WM) fiber microstructure as measured by magnetic resonance diffusion tensor image (DTI) fractional anisotropy (FA) and mean diffusivity (MD)., Methods: We recruited 17 participants diagnosed with DIP, 20 Parkinson's disease (PD) patients, and 16 normal controls (NCs) with a similar age, gender, and years of education. Subsequently, all participants underwent DTI magnetic resonance imaging scanning. To analyze the data, we utilized the software packages Functional MRI of the Brain Centre (FMRIB) Diffusion Toolbox (FDT), developed by the FMRIB laboratory at Oxford University, and tract-based spatial statistics (TBSS)., Results: The Argentina Hyposmia Rating Scale (AHRS) scores of patients in DIP group were markedly higher than those in PD patients group. Compared with the NC group, the FA values in the genu and body of the corpus callosum (CC), anterior limb of the right internal capsule, bilateral anterior corona radiata, bilateral superior corona radiata, right external capsule, and right superior fronto-occipital fasciculus (could be a part of the anterior internal capsule) were significantly decreased in the DIP group; however, no significant cluster was found in MD., Conclusions: The present study provides novel insights into the alterations in WM microstructure among DIP patients, suggesting that these methodologies have the potential to aid in the early diagnosis and treatment of DIP., (© 2024 The Author(s). Published by IMR Press.)

Antipsychotic-induced parkinsonism is an undesirable reaction from the extrapyramidal system that occurs against the background of taking antipsychotics (AP), more often in patients with schizophrenia. Antipsychotic-induced parkinsonism belongs to the group of secondary parkinsonism. Its prevalence in the world is about 36%. It is assumed that this undesirable AP reaction is genetically determined. In recent years, numerous associative genetic studies of predisposition to the development of antipsychotic-induced parkinsonism have been conducted. However, the research results are contradictory.Purpose. Review of the results of studies of genetic predictors of antipsychotic-induced parkinsonism in patients with schizophrenia.Materials and methods. We searched for full-text publications in Russian and English in the RSCI, PubMed, Web of Science, Springer databases using keywords and combined searches for words over the past decade.Results. The review considers candidate genes encoding proteins/enzymes involved in the pharmacodynamics and pharmacokinetics of AP. We analyzed 23 genome-wide studies examining 108 genetic variations, including SNV/polymorphisms of 26 candidate genes involved in the development of AIP in schizophrenic patients. Among such a set of obtained results, only 22 positive associations were revealed: rs1799732 (141CIns/Del), rs1800497 (C/T), rs6275 (C/T) DRD2; rs167771 (G/A) DRD3; VNTR*9R DAT1; rs4680 (G/A) СOMT; rs6311 (C/T) 5HTR2A; rs6318 (C/G), rs3813929 (С/Т), haplotype-997G, -759C, -697C и 68G HTR2C; rs2179652 (C/T), rs2746073 (T/A), rs4606 (C/G), rs1152746 (A/G), rs1819741 (С/Т), rs1933695 (G/A), haplotype rs1933695-G, rs2179652-C, rs4606-C, rs1819741-T и rs1152746-G, haplotype rs1933695-G, rs2179652-T, rs4606-G, rs1819741-C и rs1152746-A RGS2; haplotype TCCTC ADORA2A; rs4795390 (C/G) PPP1R1B; rs6265 (G/A) BDNF; rs12678719 (C/G) ZFPM2; rs938112 (C/A) LSMAP; rs2987902 (A/T) ABL1; HLA-B44; rs16947 (A/G), rs1135824 (A/G), rs3892097 (A/G), rs28371733 (A/G), rs5030867 (A/C), rs5030865 (A/C), rs1065852 (C/T), rs5030863 (C/G), rs5030862 (A/G), rs28371706 (C/T), rs28371725 (A/G), rs1080983 (A/G) CYP2D6. However, at the present time it should be recognized that there is no final or unique decision about the leading role of any particular SNV/polymorphism in the development of AIP.Conclusion. Disclosure of genetic predictors of AP-induced parkinsonism development may provide a key to the development of a strategy for personalized prevention and treatment of the neurological complication of AP-therapy of schizophrenia in real clinical practice.

Drug-induced parkinsonism (DIP) is the most common drug-induced movement disorder and is most commonly associated with antipsychotic drugs, monoamine reuptake inhibitors, and calcium channel blockers. DIP manifests as a typical movement disorder, which makes it practically indistinguishable from idiopathic Parkinson's disease (PD) and requires differential diagnosis. DIP symptoms develop fairly quickly (hours to weeks) after the antipsychotic is started or after the dose is increased. Therefore, DIP is predominantly a clinical diagnosis that must be kept in mind when a patient develops typical symptoms during treatment onset or increasing the dose of drugs that most often lead to such an adverse reaction (ADR). DIP evaluation includes using the Naranjo algorithm, which helps assess a causal relationship between drug intake and the development of parkinsonism symptoms. The primary DIP treatment is the reduction of the dose of the inducer drug, or its cancellation, or replacement with another drug. In patients with schizophrenia and antipsychotic-induced DIP, dose reduction, replacement with another medication, or prescription of a drug with anticholinergic activity may be possible. The awareness of the doctor and the patient about the possibility of developing this ADR is crucial in the prevention of DIP. Therefore, choosing a drug with the lowest risk of developing DIP is necessary for pharmacotherapy.

Drug-induced parkinsonism (DIP) is one of the most frequent extrapyramidal disorders that develops against the background of prescribing a large number of medications. Initially, DIP was described as an adverse drug reactions (ADRs) against the background of the use of antipsychotic drugs, but later recognized as ADRs of a number of other drugs, including prokinetics, antidepressants, calcium channel blockers and antiepileptic drugs. The relative risk of developing LIP on the background of taking typical antipsychotics increased by 2.92 times compared to patients who do not take these drugs. The risk of developing DIP in patients receiving flunarizine is increased by 2.75-4.07 times. The risk of DIP with the use of antidepressants is increased by 2.14 times, among the drugs of this group with an increased risk of DIP, the use of selective serotonin reuptake inhibitors is most often associated with DIP (relative risk 1.24). Among other antidepressants, there is evidence of the development of DIP against the background of the use of duloxetine, mirtazapine, amitriptyll clomipramine, venlafaxine, trazodone. Among anticonvulsants, DIP can rarely develop against the background of the appointment of valproic acid, gabapentin, pregabalin, carbamazepine, oxcarbazepine. The risk of DIP in patients receiving metoclopramide is extremely low (0.06%), but it is 2.16 times higher compared to people who do not take this drug. Among drugs from other groups, DIP can occur against the background of the use of lithium carbonate, tacrolimus, cyclosporine, amiodarone, captopril, amphotericin B. If DIP develops, it is necessary, if possible, to reduce the dose or cancel the inducer drug, or replace it with another drug with minimal risk of DIP. Symptoms of DIP most often regress within a few weeks or months after dose reduction or withdrawal of the drug inducer. If the symptoms persist longer, it is necessary to exclude the presence of Parkinson’s disease or dementia with with Lewy bodies.

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]

Among neurological adverse reactions in patients with schizophrenia treated with antipsychotics (APs), drug-induced parkinsonism (DIP) is the most common motility disorder caused by drugs affecting dopamine receptors. One of the causes of DIP is the disruption of neurotransmitter interactions that regulate the signaling pathways of the dopaminergic, cholinergic, GABAergic, adenosinergic, endocannabinoid, and other neurotransmitter systems. Presently, the development mechanisms remain poorly understood despite the presence of the considered theories of DIP pathogenesis. [ABSTRACT FROM AUTHOR]

Antipsychotic-induced parkinsonism (AIP) is one of the prognostically unfavorable complications of psychopharmacotherapy in patients with schizophrenia. Many studies have investigated various drugs that are used to treat this neurological side effect. This review analyzes drugs that are used and may be perspective for the treatment of AIP. We searched for full-text publications in Russian and English in the following databases: E-Library, PubMed, Web of Science, Springer, using keywords and combined word searches over the past decade (2011—2020). The review covers drugs that are promising for the correction of AIP, including anticholinergic drugs; NMDA receptor antagonists; dopamine receptor agonists; selective inhibitors of monoamine oxidase B; catecholamine transferase inhibitors; melatonin preparations; melatonin receptor agonists; benzodiazepines; herbal preparations traditionally used for the prevention and correction of extrapyramidal syndrome of various etiologies. Currently, a small number of medications are used in clinical practice for the treatment of AIP. However, not all of them are registered in the Russian Federation. Along with the differences in the mechanisms of AIP pathogenesis in specific patients, the limited choice of AIP treatments makes it difficult to solve the problem of adverse neurological complications of psychopharmacotherapy in schizophrenia.

Drug-induced parkinsonism has been commonly studied and discussed regarding antipsychotic agents, but lithium-induced parkinsonism should also be considered when patients present with parkinsonian symptoms and chronic lithium use. There are several reports of parkinsonism arising during lithium administration and regressing following its reduction or discontinuation. Our case is, to date, the first case in the literature in which vocal cord paralysis occurred as the first symptom of lithium-induced parkinsonism, contributing to confuse doctors and patients and to delay diagnosis and treatment. In our clinical case prompt withdrawal of lithium and its reintroduction at lower doses led to complete resolution of this disabling clinical presentation. This report emphasizes the importance of careful monitoring of lithium levels, especially in elderly subjects, and the need to consider lithium-induced parkinsonism even when unusual motor symptoms appear in chronic lithium users. [ABSTRACT FROM AUTHOR]

Whether there are differences in the time to onset of drug-induced parkinsonism (DIP) depending on the type of drugs causing DIP remains uncertain, so that question was investigated here using a large real-world database. Fourteen DIP-related drug categories were defined to perform a disproportionality analysis using a large Japanese pharmacovigilance database containing more than 600,000 self-reported adverse events (AEs) recorded between April 2004 and September 2021 to identify AEs indicating "parkinsonism" in association with the defined drug categories. The time from drug administration to the onset of DIP was comparatively analyzed. Results indicated that the median time to onset was shorter than 1 month in more than half of the cases of DIP; it was shortest with peripheral dopamine antagonists (median: 0.1 weeks), followed by benzodiazepine (median: 0.5 weeks), butyrophenone (median: 0.7 weeks), novel antidepressants (median: 2.5 weeks), atypical antipsychotics (median: 3.3 weeks), other antidepressants (e.g., lithium, median: 3.7 weeks), and benzamide (median: 4.5 weeks). In contrast, anti-dementia drugs, tricyclic antidepressants, and antiepileptic drugs resulted in a relatively longer time to onset (median: 9.9, 17.2, and 28.4 weeks, respectively). In addition, a maximum delay of even longer than 2 years was reported for benzamide (846 weeks), anti-Parkinsonism drugs (382 weeks), phenothiazine (232 weeks), atypical antipsychotics (167 weeks), anti-dementia drugs (161 weeks), and benzodiazepines (120 weeks). The current results suggested that the characteristics of the time to onset of DIP may substantially differ depending on the type of drug causing that DIP. This finding may help when diagnosing patients with parkinsonism. [ABSTRACT FROM AUTHOR]

Introduction: Few epidemiological studies have assessed the risk of parkinsonisms after prolonged use of neuroleptics. We aimed to examine the long-term risk of degenerative parkinsonisms (DP) associated with previous use of neuroleptics.Methods: All residents in Piedmont, Northern-west Italy, older than 39 years (2,526,319 subjects), were retrospectively followed up from 2013 to 2017. Exposure to neuroleptics was assessed through the regional archive of drug prescriptions. The development of DP was assessed using the regional archives of both drug prescriptions and hospital admissions. We excluded prevalent DP cases at baseline as well as those occurred in the first 18 months (short-term risk). The risk of DP associated with previous use of neuroleptics was examined through Cox regression, using a matched cohort design.Results: The risk of DP was compared between 63,356 exposed and 316,779 unexposed subjects. A more than threefold higher risk of DP was observed among subjects exposed to antipsychotics, compared to those unexposed (HR = 3.27, 95% CI 3.00-3.57), and was higher for exposure to atypical than typical antipsychotics. The risk decreased after 2 years from therapy cessation but remained significantly elevated (HR = 2.38, 95% CI 1.76-3.21).Conclusions: These results indicate a high risk of developing DP long time from the start of use and from the cessation for both typical and atypical neuroleptics, suggesting the need of monitoring treated patients even after long-term use and cessation. [ABSTRACT FROM AUTHOR]

Introduction Pramipexole is a dopaminergic agonist used in the treatment of Parkinson’s disease and restless leg syndrome. Although there is a lack of pharmacological options to treat drug-induced parkinsonism, not many studies have been made on the use of pramipexole in its management. There is also evidence on pramipexole effectiveness on major depressive episodes, particularly for bipolar and treatment-resistant depression. Objectives To describe a case of drug-induced parkinsonism treated with pramipexole in a complex patient with bipolar disorder type I and obsessive-compulsive disorder, long-term treated with antipsychotics and valproate. Methods We present the case of a 51-year-old woman admitted in our psychiatric inpatient unit mainly to treat a bipolar depression. She also presented a parkinsonian syndrome, and a neurological study was conducted. As a negative DaTSCAN concluded its cause to be pharmacological, we decided to stop lurasidone and initiated pramipexole. Results Guidelines suggest that drug-induced parkinsonism should be managed by discontinuing causative drugs or switching to another agent. However, we decided to use pramipexole with the aim of not only treating the parkinsonian syndrome but helping manage the depressive episode. We observed a remission of the depressive symptoms and an improvement in the parkinsonian symptoms. Conclusions Although the best way to treat drug-induced parkinsonism is to avoid its causative agents, in clinical practice it is not always possible as some patients have resistant and complex psychiatric syndromes. We suggest considering pramipexole in its management, especially when dealing with a patient with a comorbid unipolar or bipolar depression. Further research is necessary to clarify its utility. Disclosure No significant relationships.

Background: Both drug-induced Parkinsonism (DIP) and tardive dyskinesia (TD) have been shown to be associated with lower health-related quality of life (HRQOL) in schizophrenia, but few studies have examined their relative impact. Aims: This study aimed to examine and compare the association of DIP and TD with HRQOL in schizophrenia. Methods: In total, 903 patients with schizophrenia were assessed on the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). EuroQoL five-dimensional (EQ-5D-5L) utility scores were derived from PANSS scores via a previously validated algorithm and used as a measure of HRQOL. Results: In total, 160 (17.7%) participants had only DIP, 119 (13.2%) had only TD, and 123 (13.6%) had both DIP and TD. HRQOL was lowest for participants with both DIP and TD, followed by only DIP group, only TD group, and highest in the group with neither condition. HRQOL scores differed significantly between the four groups, F (3, 892) = 13.724, p < 0.001, η p 2 = 0.044). HRQOL of participants having only DIP or both DIP and TD was significantly lower than those having neither condition. There was no significant interaction between the presence of DIP and TD on the association with HRQOL. Conclusions: DIP was the main antipsychotic-induced movement disorder associated with a poorer HRQOL in patients with schizophrenia. Therefore, clinicians should focus on prevention, detection, and effective management of DIP to optimize HRQOL in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Background: The last decade has seen development of numerous novel antipsychotic drugs with unique mechanisms including long-acting formulations for clinical use. A comparative assessment of these new drugs with each other and previous antipsychotics have not been performed with regards to risk for drug-induced movement disorders (DIMD). Methods: Medline was searched from January 2010 to February 2022 for primary research articles and review articles in English using the search terms "extrapyramidal" and "tardive" with individual drug names of novel antipsychotics. Results: We identified articles describing the risk of DIMD with 6 novel antipsychotics, 4 novel formulations, and 3 experimental antipsychotics. Both short- and long-term data generally showed comparable to lower risk of DIMD with novel antipsychotics and recent long-acting formulations compared to previously marketed antipsychotics. Discussion: Several novel antipsychotics, particularly lumateperone and pimavanserin, show promise in being able to treat psychosis while reducing the risk of DIMD. Long-acting paliperidone may reduce risk of DIMD while other long-acting injectable formulations of SGA have similar risk of DIMD compared to oral formulations. New drug targets for treating psychosis without dopamine blockade also show promise. [ABSTRACT FROM AUTHOR]

The article presents a clinical case of neuroleptic malignant syndrome (NMS) and DIP after a single dose of thiorizadine, and discusses the issues of differential diagnosis and treatment methods. A 57-year-old patient with long-term remission of schizophrenia due to insomnia was prescribed thiorizadine. After a single dose, symptoms of parkinsonism in the form of hypokinesia, muscle rigidity and bradyphrenia developed and began to progress. Three weeks later NMS developed, and treatment was carried out in the intensive care unit. When signs of parkinsonism persisted, she was hospitalized in the neurological department. Regression of symptoms occurred by her taking amantadine sulfate.

The discovery of the first typical antipsychotics in the 1950s had revolutionized the treatment of many severe mental illnesses. This discovery opened the door for radical humanization and deinstitutionalization of the whole psychiatry. It also served as an impetus for the emergence of a new science, called psychopharmacology. This signaled the beginning of an era of widespread use of psychopharmacotherapy in psychiatry. However, the use of typical antipsychotics has been associated with many side effects, including severe ones, such as severe extrapyramidal syndrome, neuroleptic-induced deficit syndrome, cognitive impairment, and neuroleptic malignant syndrome. This necessitated the development of methods for correction or treatment of such side effects.Over the past decades, a number of new antipsychotics have been synthesised and approved for clinical use. Those new drugs are considered to belong to the group of so-called «atypical antipsychotics». This group, as a whole, has an improved tolerance and safety profile compared to older, conventional antipsychotics. In particular, these new drugs less often cause exactly the aforementioned side effects. Nevertheless, the problem of antipsychotic side effects and their correction is still far from being resolved. Some patients experiencing certain side effects from antipsychotic therapy do not get adequate relief from the standard pharmacological correction of those side effects.This fact stimulated our interest in the study of the possibilities of using electroconvulsive therapy as an alternative or adjuvant method for the correction of some side effects that can arise during antipsychotic therapy. In this article, we thoroughly discuss the existing evidence base regarding the effectiveness and safety of the use of electroconvulsive therapy as a corrector for certain side effects that can occur during antipsychotic therapy.

Introduction: Considering the difficulties of differentiating Parkinson’s disease (PD) from drug-induced Parkinsonism (DIP) in patients receiving antipsychotics, developing robust diagnostic tools is essential. Herein, we used the metaiodobenzylguanidine (MIBG) scan to assess its diagnostic accuracy for this purpose. Methods: 44 DIP patients and 32 patients with PD as controls were enrolled. All the participants underwent a cardiac 131I-MIBG scan. Statistical analysis was conducted to determine the significance of the results, and accuracy analyses were conducted to calculate the related sensitivity and specificity of the MIBG scan. Results: The mean age of PD and DIP groups were 62.6 ± 5.9 and 51.5 ± 10.8 years, respectively. The mean duration of drug consumption in the DIP group was 52.2 ± 29.4 days (the mean interval between drug initiation and DIP onset was 28.5 ± 20.5). Symptoms relief occurred 40 ± 24.2 days after drug discontinuation. In the PD group, 15.6% showed negative and 84.4% positive results on the MIBG scan. In the DIP group, 86.4% were negative, and the remaining were positive. The difference in MIBG uptake between the two groups was statistically significant (P-value

Competing Interests: Conflicts of interest: Ian and Fiona Coombes are immediate family members of Judith Coombes, who is a member of the Australian Prescriber Editorial Advisory Committee. Judith was excluded from editorial decision-making related to the acceptance and publication of this article.

Parkinsonism induced by dopamine receptor antagonists, traditionally considered completely reversible following offending drug withdrawal, may unmask a degenerative parkinsonism in the patients with an underlying subclinical disease. In elderly patients, parkinsonism induced by the calcium channel blockers such as piperazine derivates cinnarizine and flunarizine may persist following drug discontinuation resulting in a permanent nonprogressive syndrome fulfilling the criteria for tardive parkinsonism. Whether this outcome occurs also following exposure to dopamine receptor antagonists such as neuroleptics and benzamide derivates or represents a class effect of the voltage-gated L-type calcium channel blockers, such as cinnarizine and flunarizine, due to their complex pharmacodynamic properties remains to be established., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This case report presents the challenging clinical scenario of a middle-aged male patient with a decade-long history of psychiatric illness on chronic neuroleptic therapy. The patient's symptoms initially manifested as tremors a year ago, subsequently progressing to resting tremors, head titubation, and impaired mobility. Typically, Drug-Induced Parkinsonism (DIP) occurs within three months of initiating neuroleptic treatment, this case presents a unique and prolonged timeline, raising questions about the underlying aetiology complexed with patients' imaging studies revealing age related atrophy. The bilateral and symmetrical motor signs observed align with DIP characteristics, although studies report asymmetrical signs, introducing diagnostic complexities. This case emphasizes the need for further research on understanding the effect of chronic neuroleptic use, age-related structural alterations, and the potential unmasking of underlying Parkinsonism for improving diagnostic accuracy and tailoring effective management strategies for patients with similar challenging presentations. [ABSTRACT FROM AUTHOR]

Brainstem auditory evoked response (BAER) is a non-invasive modality that can be used to investigate brainstem neuronal function in movement disorders. The differentiation between drug-induced parkinsonism (DIP) and Parkinson's disease (PD) can be very challenging. Although PD and DIP to some extent display similar clinical symptoms, the underlying pathophysiologic mechanisms are entirely different. Given these differences in pathogenesis, and the diagnostic utility of BAER for detecting brainstem function, BAER may help to distinguish between PD and DIP. This study aimed to assess the accuracy and predictive values of BAER parameters in differentiating DIP from PD. We prospectively studied143 participants classified within three groups, including 50 controls, 57 PD, and 36 DIP. BAER was performed on all patients in the study. Patients in the DIP group were followed up for at least one year after discontinuation of the causative drug and examined for final diagnosis. We compared BAER latencies of the three groups and measured sensitivity, specificity, predictive values, likelihood ratios, and accuracy of BAER in diagnosing DIP. Waves V, I-V, and III-V latencies were significantly prolonged among the PD patients compared to the DIP and the control group; however, there were no significant differences in BAER latencies between the DIP and the control group. Waves V and I-V latencies revealed the highest accuracy (86% and 79%, respectively) in distinguishing DIP from PD with high negative predictive value(89% and 83%, respectively) as well as a high negative likelihood ratio (0.2and 0.3, respectively). This study showed that waves V and I-V latencies are significantly prolonged in PD patients compared to those with DIP, consistent with the proposed mechanisms of neurodegeneration in PD, particularly in the midbrain and pons. Consequently, BAER could be used as a useful diagnostic tool for differentiating DIP from PD. [ABSTRACT FROM AUTHOR]

Drug-induced parkinsonism (DIP) is a frequent parkinsonian syndrome that appears as a result of pharmacotherapy for the management of psychosis. It could substantially hamper treatment and therefore its diagnosis has a direct influence on treatment effectiveness. Although of such high importance, there is a lack of systematic research for developing neuroimaging-based criteria for DIP diagnostics for such patients. Therefore, the current study was aimed at applying a metabolic brain imaging approach using the 18F-FDG positron emission tomography and spatial covariance analysis to reveal possible candidates for DIP markers. As a result, we demonstrated, to our knowledge, the first attempt at the application of the Parkinson’s Disease-Related Pattern (PDRP) as a metabolic signature of parkinsonism for the assessment of PDRP expression for schizophrenia patients with DIP. As a result, we observed significant differences in PDRP expression between the control group and the groups with PD and DIP patients. Similar differences in PDRP expression were also found when the non-DIP schizophrenia patients were compared with the PD group. Therefore, our findings made it possible to conclude that PDRP is a promising tool for the development of clinically relevant criteria for the estimation of the risk of developing DIP.

Drug-induced parkinsonism is the main cause of secondary parkinsonism in the world. Antipsychotics, antidepressants, and mood stabilizers are the most common drugs implicated in the parkinsonism. This is why psychiatrists and neurologists must have deep knowledge of the diverse aspects of these disorders, to take the best diagnostic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Abstract Background Parkinson’s disease (PD) and drug-induced parkinsonism (DIP) are the major diseases of parkinsonism. To better understand parkinsonism, we aimed to assess the prevalence and incidence of PD and DIP in Korea from 2012 to 2015. Methods We used the Health Insurance Review and Assessment Service database, which covers the entire population in Korea. We used claims during 2011–2015 to assess epidemiology of PD and DIP during 2012–2015. Retrospective cross-sectional study design was employed to assess prevalence, whereas retrospective cohort study design was used to determine incidence. Patients with at least one claim with ICD-10 G20 and who received antiparkinsonian drugs for at least 60 days were classified as having PD. We excluded patients with antiparkinsonian drugs that can be used for indications other than PD. Patients with at least one claim with ICD-10 G211 or G251 during the prescription period of drugs that are frequently related with DIP were classified as having DIP. Incident cases had a disease-free period of 1 year before diagnosis. To evaluate the significance of changes in the prevalence or incidence over time, Poisson regression was used to determine p for trend. Results The prevalence of PD increased from 156.9 per 100,000 persons in 2012 to 181.3 per 100,000 persons in 2015 (p for trend

Drugs, such as dopamine receptor blockers or dopamine depleters, produce a functional dopamine-deficient state mimicking parkinsonism, but presentation with a progressive supranuclear palsy (PSP) is a rare manifestation. We report three patients with a PSP-like presentation, with symmetrical parkinsonism, postural instability, and gaze palsy due to drugs, such as metoclopramide, risperidone, and olanzapine, which reversed after drug withdrawal.

Among neurological adverse reactions in patients with schizophrenia treated with antipsychotics (APs), drug-induced parkinsonism (DIP) is the most common motility disorder caused by drugs affecting dopamine receptors. One of the causes of DIP is the disruption of neurotransmitter interactions that regulate the signaling pathways of the dopaminergic, cholinergic, GABAergic, adenosinergic, endocannabinoid, and other neurotransmitter systems. Presently, the development mechanisms remain poorly understood despite the presence of the considered theories of DIP pathogenesis.

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]

Tremor is a commonly encountered condition in the primary care setting and can manifest at rest, with action, or both. Common causes include Parkinson disease, essential tremor, and drug-induced tremor. In this article, the authors discuss how to examine a patient with tremor and which features of the history and examination can help clue the provider in to the appropriate diagnosis. They also review treatments for varying types of tremor and when referral to a neurologist may be necessary., Competing Interests: Disclosure None of the authors have commercial or financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

BackgroundSulpiride is a highly selective dopamine D2 receptor antagonist and is commonly used in psychiatric disorders, Tourette syndrome, peptic ulcer disease (PUD), and gastroesophageal reflux disease (GERD). However, sulpiride has been recognized as a potential cause of drug-induced parkinsonism (DIP) for a long time. In this study, we aimed to focus on analysis of sulpiride-induced parkinsonism (SIP) in PUD and GERD patients based on a nationwide population.MethodsData were obtained from the Taiwan’s National Health Insurance Research Database. The study enrolled 5,275 PUD or GERD patients, of whom were divided into two groups, based on their exposure (1,055 cases) or non-exposure (4,220 cases) to sulpiride.ResultsDuring the study period (2000–2012), the incidence rate of parkinsonism was 261.5 and 762.2 per 100,000 person-years in the control and sulpiride-treated groups, respectively. For patients with at least 14 days of prescription for sulpiride, the adjusted hazard ratio (aHR) was 2.89, 95% confidence interval (CI): 2.04-4.11. Patients with age more than 65 years (aHR = 4.99, 95% CI = 2.58-9.65), hypertension (aHR = 2.39, 95% CI = 1.49-3.82), depression (aHR = 2.00, 95% CI = 1.38-2.91), and anxiety (aHR = 1.45, 95% CI = 1.01-2.09) had significant higher risk of developing parkinsonism. An average annual cumulative sulpiride dose > 1,103 mg was accompanied by the greatest risk of SIP; sulpiride use for ≥ 9 days is a cut-off point for predicting future SIP.ConclusionAt the population level, sulpiride may be frequently prescribed and apparently effective for PUD and GERD. SIP is associated with older age, hypertension, depression or anxiety comorbidities. Physicians should be aware of the neurogenic adverse effects, even when the drug is only used in low-dose or a short duration.

This report describes a case of likely drug-induced Parkinsonism (DIP) identified by the pharmacist. A 54-year-old female patient was referred by a physician to the pharmacist in a rural, integrated care team for a comprehensive medication review (CMR) to address the patient’s concerns of possible Parkinson’s disease (PD). While PD may occur over the progression of age, medications that affect dopamine transport can also cause DIP, a secondary form of Parkinson’s disease. Although PD and DIP may be clinically indistinguishable, differentiation may be possible by reviewing a patient’s medication history for any potential causative drugs correlating to the timeline of the onset of symptoms. In this case, the pharmacist reviewed the medication profile and identified medications that could be responsible for causing DIP, specifically bupropion. The pharmacist suggested discontinuing bupropion and identifying another option for treating depression. The patient appreciated the suggestion and education, but ultimately preferred continuing her bupropion therapy instead of discontinuing therapy or changing to an alternative agent. At a follow-up meeting with the pharmacist, not only was the patient still experiencing tremors despite taking carbidopa/levodopa, but additional medications known to be potential inducers of tremors were added to her regimen. Although the pharmacist repeatedly discussed DIP with the patient and believed stopping bupropion would determine whether her Parkinsonism was PD or DIP, ultimately the patient continued taking bupropion because of concerns related to depression severity and the impact on her well-being. The patient’s wishes were respected.

Objective: The objective of this study is to examine the effectiveness of an accelerometer-based compact system in detecting and quantifying drug-induced parkinsonism (DIP) in patients with schizophrenia.Method: A pilot study controlled clinical trial comprising 6 people with schizophrenia and 11 control subjects was conducted at Alfred Health, Melbourne. Participants had their movements assessed using Barnes Akathisia Rating Scale (BARS), Simpson Angus Scale (SAS) and Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) followed by an assessment of gait using three triaxial accelerometers.Results: Median BARS, SAS, MDS-UPDRS III and accelerometer scores were significantly higher for patients with schizophrenia than controls. Accelerometers detected three times more rest tremor than clinical rating scales. Patients with schizophrenia had 70% of their dynamic acceleration at frequencies between 4 and 10 Hz, which is almost twice that observed in the control population (38%). Accelerometer scores were significantly correlated with BARS scores.Conclusion: Accelerometers were able to accurately detect patients with DIP better than some clinical rating scale including the SAS. Further larger-scale studies must be conducted to further demonstrate the accuracy of accelerometers in detecting DIP. [ABSTRACT FROM AUTHOR]