Gastroparesis treatment options metoclopramide and prucalopride: analysis of the FDA Adverse Event Reporting System (FAERS) database.

BACKGROUND: We aimed to examine the common adverse drug reactions (ADRs) of metoclopramide, FDA-approved for treating many gastrointestinal conditions including gastroparesis, and prucalopride, FDA-approved for treating chronic idiopathic constipation but used off-label for other gastrointestinal conditions including gastroparesis. RESEARCH DESIGN AND METHODS: The FDA Adverse Event Reporting System (FAERS) was analyzed from January 2013 to December 2023. ADR reports regarding use of only metoclopramide or prucalopride were analyzed following exclusion of reports indicating use for treatment of non-gastrointestinal conditions. RESULTS: Analysis of 1,085 reports on metoclopramide revealed tardive dyskinesia (n = 393, 36.2%) and dystonia (n = 170, 15.7%) among the most reported ADRs in addition to QTc prolongation (n = 16, 1.5%) with progression to Torsade de pointes (n = 5, 0.5%) and triggering of pheochromocytoma crisis (n = 24, 2.2%). Analysis of 865 reports on prucalopride revealed headache (n = 120, 13.9%), diarrhea (n = 116, 13.4%), and abdominal pain (n = 100, 11.6%) as the most common ADRs with 22 reports (2.5%) of dystonia with the use of prucalopride. CONCLUSIONS: This FAERS database analysis shows post-marketing reports of ADRs from metoclopramide most frequently include tardive dyskinesia, dystonia, and tremor in addition to potentially fatal arrhythmias such as Torsade de pointes. Consumers of prucalopride may also be at risk of dystonia and other ADRs.

Immunosenescence-related T cell phenotypes and white matter in schizophrenia patients with tardive dyskinesia.

Schizophrenia patients with tardive dyskinesia (TD) are associated with accelerated biological aging, immunological dysfunction, and premature morbidity and mortality. Older individuals are particularly vulnerable to TD development. As a characteristic of immunosenescence, alterations in the relative proportions of naïve or memory T cell subpopulations may be negatively or positively associated with brain structure abnormalities; however, whether these changes are correlated with TD remains unclear. In this study, we investigated correlations between distributions of T cell phenotypes and brain structure abnormalities (especially white matter) in schizophrenia patients with (TD) and without (NTD) TD (n = 50 and 58, respectively) relative to healthy controls (HC, n = 41). Immune markers, including naïve (CD45RA+), memory (CD45RO+), and apoptotic (CD95+) CD4+ and CD8+ T cells, were examined by flow cytometry, as were the intracellular levels of cytokines (interferon (IFN)-γ, interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α) in CD8 + CD45RA + CD95+ and CD8 + CD45RO + CD95+ T cells. MRI was employed to evaluate the fractional anisotropy (FA) of white matter tracts and subcortical volumes, following published routines. The percentage of CD8 + CD45RO + CD95+ T cells was higher in TD compared with NTD and HC groups and correlated with the choroid plexus volume in TD group. The intracellular level of IFN-γ in CD8 + CD45RO + CD95+ T cells, the FA of the fornix/stria terminalis, and the pallidum volume were correlated with orofacial TD, whereas the FAs of the inferior fronto-occipital fasciculus, cingulum, and superior longitudinal fasciculus were correlated with limb-truncal TD. These findings provide preliminary evidence that the association between immunosenescence-related T cell subpopulations and brain structure may underline the pathological process of TD.

An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders.

Drug-induced movement disorders (DIMDs) are associated with use of dopamine receptor blocking agents (DRBAs), including antipsychotics. The most common forms are drug-induced parkinsonism (DIP), dystonia, akathisia, and tardive dyskinesia (TD). Although rare, neuroleptic malignant syndrome (NMS) is a potentially life-threatening consequence of DRBA exposure. Recommendations for anticholinergic use in patients with DIMDs were developed on the basis of a roundtable discussion with healthcare professionals with extensive expertise in DIMD management, along with a comprehensive literature review. The roundtable agreed that "extrapyramidal symptoms" is a non-specific term that encompasses a range of abnormal movements. As such, it contributes to a misconception that all DIMDs can be treated in the same way, potentially leading to the misuse and overprescribing of anticholinergics. DIMDs are neurobiologically and clinically distinct, with different treatment paradigms and varying levels of evidence for anticholinergic use. Whereas evidence indicates anticholinergics can be effective for DIP and dystonia, they are not recommended for TD, akathisia, or NMS; nor are they supported for preventing DIMDs except in individuals at high risk for acute dystonia. Anticholinergics may induce serious peripheral adverse effects (e.g., urinary retention) and central effects (e.g., impaired cognition), all of which can be highly concerning especially in older adults. Appropriate use of anticholinergics therefore requires careful consideration of the evidence for efficacy (e.g., supportive for DIP but not TD) and the risks for serious adverse events. If used, anticholinergic medications should be prescribed at the lowest effective dose and for limited periods of time. When discontinued, they should be tapered gradually.

Investigating Real-World Benztropine Usage Patterns in Movement Disorders: Claims Analysis and Health Care Provider Survey Results.

Objective: To evaluate real-world treatment patterns for patients initiating benztropine and to understand treatment approaches in patients with drug-induced movement disorders from a health care provider perspective.Methods: A retrospective claims analysis was conducted among patients with evidence of benztropine initiation from January 2017 through March 2020 to assess treatment patterns and patient health care resource utilization. Subsequently, a 30-minute, United States-based online survey fielded from December 2021 to January 2022 was sent to physicians, nurse practitioners, and physician assistants who reported a primary care or psychiatry specialty currently treating drug-induced movement disorders and prescribed benztropine.Results: The health care claims analysis included 112,542 patients. Polypharmacy and multiple comorbidities were frequent characteristics in this population; 54.1% of patients had ≥ 2 comorbidities at baseline, and 59.1% had claims for > 10 medications. Benztropine was used for > 3 months in > 50% of the population. Health care costs and resource utilization were high, with mean all-cause pharmacy and outpatient costs totaling $11,755. Survey results from 349 primary care or psychiatry health care providers indicated that benztropine is often used in non-tardive dyskinesia drug-induced movement disorders but frequently continued for > 3 months or used in tardive dyskinesia. In this study, psychiatry providers prescribed benztropine in line with guideline recommendations more often than primary care providers; however, < 40% indicated familiarity with 2020 American Psychiatric Association Practice Guideline for the Treatment of Patients with Schizophrenia.Conclusions: These complementary analyses suggest that benztropine is used long-term in non-tardive dyskinesia drug-induced movement disorders and in tardive dyskinesia despite risks of worsening tardive dyskinesia or adverse effects.Prim Care Companion CNS Disord 2023;25(4):22m03472. Author affiliations are listed at the end of this article.

Levodopa/Carbidopa to Augment the Treatment of Amblyopia: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the use of levodopa/carbidopa to augment the treatment of amblyopia. METHODS: Literature searches for English language studies were last conducted in October 2022 in the PubMed database with no date restrictions. The combined searches yielded 55 articles, of which 23 were reviewed in full text. Twelve of these were considered appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. Nine studies were rated level I, and 3 studies were rated level II; there were no level III studies. RESULTS: The duration of treatment was limited to 3 to 16 weeks because of concern about long-term adverse effects such as tardive dyskinesia. This complication was not reported in any of the study participants. The dose of levodopa ranged from 1.5 to 8.3 mg/kg/day, generally divided into 3 daily doses. The carbidopa dose was approximately 25% of the levodopa dose in all treatments. Evidence from these studies indicates that augmenting traditional patch occlusion therapy with the oral administration of levodopa/carbidopa can improve the vision of amblyopic children, but the effect was small (0.17-0.3 logarithm of the minimum angle of resolution [logMAR] units) and only statistically significant when compared with patching alone in 2 of the 12 studies cited. Regression of vision was reported in the majority of studies (9 of 12 reported; range, 0-0.17 logMAR unit regression) after discontinuation of therapy. Short-term side effects of the medications were not consistently reported but were most frequently mild and included headache and nausea. CONCLUSIONS: The best available evidence is currently insufficient to show that augmenting amblyopia therapy using up to 16 weeks of levodopa/carbidopa will result in meaningful improvement in visual acuity. Given the potential for significant side effects such as tardive dyskinesia with long-term therapy, levodopa/carbidopa does not appear to be a viable option for amblyopia therapy FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Effect of rs1108580 of DBH and rs1006737 of CACNA1C on Cognition and Tardive Dyskinesia in a North Indian Schizophrenia Cohort.

Genetic perturbations in dopamine neurotransmission and calcium signaling pathways are implicated in the etiology of schizophrenia. We aimed to test the association of a functional splice variant each in Dopamine ß-Hydroxylase (DBH; rs1108580) and Calcium voltage-gated channel subunit alpha1 C (CACNA1C; rs1006737) genes in these pathways with schizophrenia (506 cases, 443 controls); Abnormal Involuntary Movement Scale (AIMS) scores in subjects assessed for tardive dyskinesia (76 TD-positive, 95 TD-negative) and Penn Computerized Neurocognitive Battery (PennCNB) scores (334 cases, 234 controls). The effect of smoking status and SNP genotypes on AIMS scores were assessed using ANOVA; health status and SNP genotypes on three performance functions of PennCNB cognitive domains were assessed by ANCOVA with age and sex as covariates. Association with Positive and Negative Syndrome Scale (PANSS) scores in the TD cohort and cognitive scores in healthy controls of the cognition cohort were tested by linear regression. None of the markers were associated with schizophrenia. Smoking status [F(2, 139) = 10.6; p = 5 × 10-5], rs1006737 [F(2, 139) = 7.1; p = 0.001], TD status*smoking [F(2, 139) = 8.0; p = 5.0 × 10-4] and smoking status*rs1006737 [F(4, 139) = 2.7; p = 0.03] had an effect on AIMS score. Furthermore, rs1006737 was associated with orofacial [F(2, 139) = 4.6; p = 0.01] and limb-truncal TD [(F(2, 139) = 3.8; p = 0.02]. Main effect of rs1108580 on working memoryprocessing speed [F(2, 544) = 3.8; p = 0.03] and rs1006737 on spatial abilityefficiency [F(1, 550) = 9.4; p = 0.02] was identified. Health status*rs1006737 interaction had an effect on spatial memoryprocessing speed [F(1, 550) = 6.9; p = 0.01]. Allelic/genotypic association (p = 0.01/0.03) of rs1006737 with disorganized/concrete factor and allelic association of rs1108580 (p = 0.04) with a depressive factor of PANSS was observed in the TD-negative subcohort. Allelic association of rs1006737 with sensorimotor dexterityaccuracy (p = 0.03), attentionefficiency (p = 0.05), and spatial abilityefficiency (p = 0.02); allelic association of rs1108580 with face memoryaccuracy (p = 0.05) and emotionefficiency (p = 0.05); and allelic/genotypic association with emotionaccuracy (p = 0.003/0.009) were observed in healthy controls of the cognition cohort. These association findings may have direct implications for personalized medicine and cognitive remediation.

Recent Updates on the Development of Deuterium-Containing Drugs for the Treatment of Cancer.

Cancer is one of the deadliest diseases in the world. In 2020, 19.3 million cancer cases and 10 million deaths were reported in the world. It is supposed that the prevalence of cancer cases will rise to 28.4 million by 2040. Chemotherapy-based regimens have a narrow therapeutic index, severe adverse drug reactions, and lack metabolic stability. Besides, the metabolism of anticancer produces several non-active and toxic metabolites that reduce exposure of the target site to the parent drug. Therefore, developing better-tolerated and effective new anticancer drugs and modification of the existing anticancer drugs to minimize toxicity and increase efficacy has become a very urgent need. Deuterium incorporation reduces the metabolism of certain drugs that are breakdown by pathways involving hydrogen-carbon bond scission. For example, CYP450 mediated oxidative metabolism of drugs that involves the breakdown of a hydrogen-carbon bond affected by deuteration. Deuterium incorporation into the drug increases the half-life and reduces the dose, which provides better safety and efficacy. Deutetrabenazine is the first deuterated form of tetrabenazine approved to treat chorea associated with Huntington's disease and tardive dyskinesia. The study revealed that Deutetrabenazine has fewer neuropsychiatric side effects with favorable safety than tetrabenazine. The current review highlights the deuterium kinetic isotope effect on drug metabolism, deuterated compound pharmacokinetic property, and safety profile. Besides, this review explains the deuterated anticancer drug development update status.

Tardive dyskinesia in Chinese patients with schizophrenia: Prevalence, clinical correlates and relationship with cognitive impairment.

OBJECTIVE: Tardive dyskinesia (TD) has a high prevalence and is one of the distressing side effects of antipsychotic medications. Few studies have explored the relationship between TD, clinical correlates, and cognition. The aim of this study was to assess the prevalence, clinical correlates and cognitive impairment of co-occurring TD in Chinese patients with schizophrenia. METHODS: We recruited 655 patients with chronic schizophrenia who met the DSM-IV diagnostic criteria for schizophrenia and collected clinical and demographic data. All patients were assessed using the Abnormal Involuntary Movement Scale (AIMS) for the severity of TD, Positive and Negative Syndrome Scale (PANSS) for psychopathological symptoms, and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) for cognition. RESULTS: The overall TD prevalence was 41.1%, 42.9% (246/574) in men and 28.4% (23/81) in women (χ2 = 6.1 df = 1, p < 0.05). There were significant differences in age, sex, duration of illness, number of hospitalizations, drug type, smoking and PANSS negative symptom subscore between TD and non-TD groups (all p < 0.05). Moreover, patients with TD scored lower for immediate memory, attention, delayed memory, and RBANS total scores (all p < 0.05). Logistic regression showed a significant correlation between TD and age, sex, drug type and attention subscore. CONCLUSION: Our results suggest that multiple demographic and clinical variables may be associated with the development of TD. Moreover, TD patients may exhibit more cognitive impairment than non-TD patients.

Correlation of Blood Biochemical Markers with Tardive Dyskinesia in Schizophrenic Patients.

Objective: Oxidative stress factors and proinflammatory cytokines had been found to be involved in the pathogenesis of patients with tardive dyskinesia (TD). This study assumes that blood biochemical markers would have a link with TD in schizophrenia patients. To explore the correlation between blood biochemical markers and tardive dyskinesia in patients with schizophrenia (SCH). Methods: From January 2010 to August 2021, the inpatients who met the diagnostic criteria of schizophrenia in the Chinese Classification and Diagnosis Criteria of Mental Disorders (DSM-4) and the American Diagnostic and Statistical Manual of Mental Disorders (DSM-4) were followed up in the psychiatric outpatient department of Jinxia Street Community Health Service Center, Longhu District, Shantou City. The diagnostic criteria of Abnormal Involuntary Movement Scale (AIMS) used in the TD study of Schooler and Kane were used to screen the patients. Patients were divided into the schizophrenia (SCH group) and the schizophrenia with TD groups (TD group). Oxidative stress factors including Superoxide Dismutase1 (SOD1), Glutathione Peroxidase1 (GPX1), Malondialdehyde1 (MDA1), Catalase Activity1 (CAT1), and brain-derived neurotrophic factor 1 (BDNF1) and some inflammatory cytokines including interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), serum tumor necrosis factor (TNF-α), prolactin, estrogen, and cortisol were measured in 121 schizophrenic patients with tardive dyskinesia and 118 schizophrenic patients. The correlation analysis was conducted on the data. Results: Age and female were immutable risk factors for the development of TD, and there were significant differences in blood biochemical indices GPX1, MDA1, CAT1, and TNF-α in schizophrenic patients with and without TD. Conclusion: This study supports that oxidative stress and immune disorders are associated with TD patients. Blood biochemical markers GPX1, MDA1, CAT1, and TNF-α may play an important role in the pathogenesis of schizophrenia combined with TD patients, and they may be useful in the diagnosis of schizophrenia with tardive dyskinesia.

Prevalence, clinical correlates and risk factors associated with Tardive Dyskinesia in Chinese patients with schizophrenia.

Tardive Dyskinesia (TD) is a serious, nonrhythmic and iatrogenic movement disorder, and is a common comorbidity in patients with schizophrenia (SZ). The main goal of this study was to investigate the prevalence, clinical correlates, and risk factors of TD in Chinese patients with chronic SZ, which has not been fully studied. This study adopted a cross-sectional design. A total of 901 Chinese inpatients with SZ were recruited between 2008 and 2011. We used the Abnormal Involuntary Movement Scale (AIMS) to measure the severity of TD, and the Positive and Negative Syndrome Scale (PANSS) was used to measure the psychopathological symptoms of SZ. Blood samples were also collected for routine blood tests, including the levels of triglyceride (TG), cholesterol (CHO), HDL-cholesterol (HDL-CHO), LDL-cholesterol (LDL-CHO), Apolipoprotein A1 (ApoA1), and Apolipoprotein B (ApoB). Overall, 36% of patients with SZ had TD. Compared with the non-TD patients, the TD patients were more likely to be men, had older age, lower education level, higher smoking rate, higher hospitalization frequency, and longer duration of illness (DOI). Further, compared with the non-TD patients, the TD patients had higher PANSS total, PANSS negative subscale, and cognitive subscale scores, but had lower depressive subscale scores and lower mean levels of metabolic biomarkers, including TG, CHO, HDL-CHO, LDL-CHO, ApoA1 and ApoB. Moreover, binary regression analysis showed that antipsychotic type, BMI, gender, age, HDL-CHO, and ApoB were associated with TD. Our findings indicate that TD is a common movement disorder in patients with chronic SZ, with certain demographic and clinical variables being risk factors for the development of TD.

Genetic association study detected misalignment in previous whole exome sequence: association study of ZNF806 and SART3 in tardive dystonia.

Tardive dystonia is one of the most serious types of extrapyramidal symptoms that antipsychotics can cause. There is no established treatment to relieve this symptom, and its etiology is unclear. Recently, we identified very rare single-nucleotide polymorphisms (SNPs) on ZNF806 and SART3 by exome sequencing in three patients with profoundly severe tardive dystonia. Here, we conducted an association study (case, N = 16 vs. control, N = 96) on the rarest SNP selected from each gene. The results showed that rs2287546 on SART3 was not related to tardive dystonia and that rs4953961 on ZNF806 was a heterozygote in all the subjects, implying the absence of a rare SNP in this locus. We found three other genomic regions with high similarity to the relevant region on ZNF806 by BLAT searches. This strongly suggested a misalignment error in this region in our previous exome sequence. In conclusion, ZNF806 and SART3 are unlikely to be related to tardive dystonia.

Clinical Spectrum of Drug-Induced Movement Disorders: A Study of 97 Patients.

Background: Drug-induced movement disorders (DIMDs) are commonly encountered, but an often-under-reported subgroup of movement disorders. Objectives: We aimed to highlight the spectrum of DIMDs in patients taking different groups of drugs at our movement disorder center. Methods: It is a cross-sectional descriptive study including 97 consecutive DIMDs patients diagnosed over the past two years (2017-2019). Results: The mean ± standard deviation (SD) age of our study population was 35.89 ± 17.8 years (Range-2-80 years). There were 51 males and 46 females. Different DIMDs observed included tardive dystonia (n = 41; 42.2%), postural tremor (n = 38; 39.2%), parkinsonism (n = 32; 33%), tardive dyskinesia (n = 21; 21.6%), acute dystonia (n = 10; 10.3%), neuroleptic malignant syndrome (NMS) (n = 2; 2.1%), and others [(n = 10; 10.30%) including chorea and stereotypy each in 3; acute dyskinesia in 2; and myoclonic jerks and acute akathisia each in 1 patient]. Of these 97 patients, 49 had more than one type of DIMDs while 48 had a single type of DIMDs. In our study 37 (38%) patients had received non-dopamine receptor blocking agents (non-DRBA), 30 (31%) patients had received dopamine receptor blocking agents (DRBA), and 30 (31%) patients had received both DRBA and non-DRBA. Conclusions: Tardive dystonia was the most common DIMDs observed in our study. Our DIMDs patients were younger than other reported studies. We observed a significant number of non-DRBA drugs causing DIMD in our study as compared to previous studies. Drug-induced parkinsonism (DIP) was the most common DIMDs in the DRBA group. Tardive dystonia was the most common DIMDs seen in DRBA + non-DRBA group and the second most common in the DRBA and non-DRBA group. The postural tremor was the most common DIMDs in the non-DRBA group.

The effect of rs1076560 (DRD2) and rs4680 (COMT) on tardive dyskinesia and cognition in schizophrenia subjects.

OBJECTIVE: The aim of the study is to test the association of a functional variant each in DRD2 and COMT genes with schizophrenia and its endophenotypes. BASIC METHODS: Effect of two functional variants rs1076560 in DRD2 and rs4680 in COMT on (1) schizophrenia (502 cases, 448 controls) diagnosed by Diagnostic and Statistical Manual of Mental Disorders-IV criteria and in subsets with (2) tardive dyskinesia (80 positive, 103 negative), assessed by Abnormal Involuntary Movement Scale (AIMS), positive and negative symptoms assessed by Positive and Negative Syndrome Scale (PANSS) and (3) cognition (299 cases, 245 controls), estimated by Penn Computerized Neurocognitive Battery, were analysed either using analysis of variance (ANOVA) or regression analysis. MAIN RESULTS: No association of two SNPs with schizophrenia, but association of rs4680 (P < 0.05) with tardive dyskinesia was observed. On ANOVA, main effect of smoking [F(2,148) = 16.3; P = 3.9 × 10]; rs4680 [F(2,148) = 3.3; P = 0.04] and interaction effect of tardive dyskinesia-status*Smoking [F(2,148) = 5.4, P = 0.006]; Smoking*rs1076560 [F(3,148) = 3.6; P = 0.01]; Smoking*rs4680 [F(4,148) = 5.3; P = 4.7 × 10] were significant with AIMS tardive dyskinesia score. The main effect of rs1076560 [F(2,148) = 4.5; P = 0.013] and rs4680 [F(2,148) = 4.0; P = 0.02] were significant with limb truncal tardive dyskinesia. Allelic/genotypic (P = 0.004/P = 0.01) association of rs1076560 with negative scale of PANSS in tardive dyskinesia-negative; diminished expression factor of PANSS in tardive dyskinesia-negative subcohort (allelic/genotypic P = 3.3 × 10/6.6 × 10) and tardive dyskinesia cohorts (P = 0.003/0.002); genotypic association (P = 0.05) with disorganised/concrete factor in tardive dyskinesia-positive subcohorts were observed by regression analysis using gPLINKv2.050. Further allelic/genotypic (P = 0.02) association of rs4680 with depressed factor of PANSS in tardive dyskinesia cohort was observed. Allelic/genotypic association of rs1076560 with abstraction and mental flexibilityaccuracy (P = 0.03/0.04), abstraction and mental flexibilityefficiency (P = 0.01/0.02); allelic association with spatial abilityprocessing speed (P = 0.03), emotionefficiency (P = 0.05); and with spatial abilityefficiency (genotypic, P = 0.05) in healthy controls and allelic association of rs4680 with emotionefficiency in cases with schizophrenia (P = 0.04) were notable. PRINCIPAL CONCLUSION: Dopaminergic genes seem to contribute to tardive dyskinesia and cognition warranting replication.

Treatment of Secondary Chorea: A Review of the Current Literature.

Background: Chorea consists of involuntary movements affecting the limbs, trunk, neck or face, that can move from one body part to another. Chorea is conceptualized as being "primary" when it is attributed to Huntington's disease (HD) or other genetic etiologies, or "secondary" when it is related to infectious, pharmacologic, metabolic, autoimmune disorders, or paraneoplastic syndromes. The mainstay of the secondary chorea management is treating the underlying causative disorder; here we review the literature regarding secondary chorea. We also discuss the management of several non-HD genetic diseases in which chorea can be a feature, where metabolic targets may be amenable to intervention and chorea reduction. Methods: A PubMed literature search was performed for articles relating to chorea and its medical and surgical management. We reviewed the articles and cross-references of pertinent articles to assess the current clinical practice, expert opinion, and evidence-based medicine to synthesize recommendations for the management of secondary chorea. Results: There are very few double-blind randomized controlled trials assessing chorea treatments regardless of etiology. Most recommendations are based on small open-label studies, case reports, and expert opinion. Discussion: Treatment of secondary chorea is currently based on expert opinion, clinical experience, and small case studies, with limited evidence-based medical data. When chorea is secondary to an underlying infection, medication, metabolic abnormality, autoimmune process, or paraneoplastic illness, the movements typically resolve following treatment of the underlying disease. Tardive dyskinesia is most rigorously studied secondary chorea with the best evidence-based medicine treatment guidelines recommending the use of pre-synaptic dopamine-depleting agents. Even though there is an insufficient pool of EBM, small clinical trials, case reports, and expert opinion are valuable for guiding treatment and improving the quality of life for patients with chorea. Highlights: There is a dearth of well-controlled studies regarding the treatment of chorea. Expert opinion and clinical experiences are fundamental in guiding chorea management and determining successful treatment. In general, secondary chorea improves with treating the underlying medical abnormality; treatments include antibiotics, antivirals, immunosuppression, dopamine depleting agents, chelation, and supportive care.

Assesment of Risk Factors for Tardive Dyskinesia.

Objective: Aim of the study is to evaluate sociodemographic and clinical features that may be associated with the development of Tardive dyskinesia (TD). Methods: 80 patients attending an outpatient psychiatry clinic in Istanbul, Turkey were divided into TD (n = 50) and control groups (CG) (n = 30). Sociodemographic and clinical data was collected through face-to-face interviews and a retrospective search of medical records. Results: There was a significant difference between TD and control group (CG) in terms of mean; onset of psychiatric disease at or after 35 years of age; first use of APD at or after 35 years of age; use of long-acting injectable APD; history of extrapyramidal side-effects; history of akathisia and family history of psychiatric disease. There was no significant difference between the two groups in terms of DSM- IV-based psychiatric diagnosis distributions, the existence of complete recovery periods during the course of the disease; total duration of APD use for at least 10 years; APD holidays; regular APD use; history of ECT and smoking or alcohol and substance abuse/addiction. Conclusion: Advancing age seemed to be the most significant risk factor in the development of TD. Clinicians need to be cautious about TD when prescribing APD for elderly patients.

A Modified Delphi Consensus Study of the Screening, Diagnosis, and Treatment of Tardive Dyskinesia.

OBJECTIVE: A nominal group process followed by a modified Delphi method was used to survey expert opinions on best practices for tardive dyskinesia (TD) screening, diagnosis, and treatment and to identify areas lacking in clinical evidence. PARTICIPANTS: A steering committee of 11 TD experts met in nominal group format to prioritize questions to be addressed and identify core bibliographic materials and criteria for survey panelists. Of 60 invited experts, 29 (23 psychiatrists and 6 neurologists) agreed to participate. EVIDENCE: A targeted literature search of PubMed (search term: tardive dyskinesia) and recommendations of the steering committee were used to generate core bibliographic material. Inclusion criteria were as follows: (1) review articles, meta-analyses, guidelines, or clinical trials; (2) publication in English between 2007 and 2017; (3) > 3 pages in length; and (4) publication in key clinical journals with impact factors ≥ 2.0. Of 29 references that met these criteria, 18 achieved a score ≥ 5 (calculated as the number of steering committee votes multiplied by journal impact factor and number of citations divided by years since publication) and were included. CONSENSUS PROCESS: Two survey rounds were conducted anonymously through electronic media from November 2017 to January 2018; responses were collected, collated, and analyzed. Respondent agreement was defined a priori as unanimous (100%), consensus (75%-99%), or majority (50%-74%). For questions using a 5-point Likert scale, agreement was based on percentage of respondents choosing ≥ 4 ("agree completely" or "agree"). Round 1 survey included questions on TD screening, diagnosis, and treatment. Round 2 questions were refined per panelist feedback and excluded Round 1 questions with < 25% agreement and > 75% agreement (unless feedback suggested further investigation). CONCLUSIONS: Consensus was reached that (1) a brief, clinical assessment for TD should be performed at every clinical encounter in patients taking antipsychotics; (2) even mild movements in 1 body area may represent possible TD; (3) management requires an overall evaluation of treatment, including reassessment of antipsychotics and anticholinergics as well as consideration of vesicular monoamine transporter 2 (VMAT2) inhibitors; and (4) informed discussions with patients/caregivers are essential.

A preliminary exome sequence in three patients with tardive dystonia.

Tardive dystonia is one of the most serious adverse events that can be caused by antipsychotic treatment, but few studies have examined the etiology of tardive dystonia, and no genetic study using a next-generation sequencing technique has been performed to date. We conducted exome sequencing in three subjects with severe tardive dystonia. We analyzed the results focusing on candidate genes of primary dystonia, for example, TOR1A, GCH1, TH, THAP1, and SGCE. There were no single-nucleotide polymorphisms of these dystonia genes that were commonly shared among our subjects. Instead, the results revealed the presence of rare mutations (minor allele frequency <0.01) on the ZNF806 and SART3 genes in all three patients. This is the first study to analyze whole-exonic regions of the genomes of patients with tardive dystonia. These results were only preliminary, but they suggest that subjects presenting with tardive dystonia induced by antipsychotic treatment can have a genetic predisposition to tardive dystonia.