Prevalence Of Tardive Dyskinesia Research Articles

Prevalence and Correlates of Extrapyramidal Side Effects Among Patients with Schizophrenia Spectrum Disorders on Typical and Atypical Antipsychotics

Background: Antipsychotic medication for the treatment of schizophrenia spectrum disorders are associated with adverse effects with extrapyramidal side effects constituting one of the most notable effects associated with poor medication adherence and poor quality of life. Aims: The study aims to compare the prevalence of extrapyramidal side effects (EPSE), among patients with schizophrenia spectrum disorders on typical and atypical antipsychotic medications. The secondary aim is to determine the association of extra-pyramidal side effects with socio-clinical variables. Methodology: A cross-sectional hospital-based study with systematic random sampling recruitment of 340 participants and 303 completed the study. Variables with significant association on chi square analysis were subjected to logistic regression analysis. Results: The overall prevalence of extrapyramidal side effects among patients with schizophrenia spectrum disorder on antipsychotic medication was 42.6 %. The prevalence of tardive dyskinesia, parkinsonism and akathisia were 7.9 %, 38.6 and 3.6 %, respectively. The prevalence of extra-pyramidal side effects due to use of typical, atypical and combination drug was 44.4 %, 51.2 % and 34.5 %, respectively with haloperidol (59.4 %) and risperidone (71.4 %) having the greatest effect. Being elderly was associated with tardive dyskinesia, duration of treatment, severity of illness and type of illness with parkinsonism and severity of illness with akathisia. Conclusion: The findings of this study support the high prevalence of extrapyramidal side effects from either using typical and atypical antipsychotic medications. Therefore, Clinicians should discuss on these side effects and proffer possible solutions with their patients prior to commencement of antipsychotic medications in order to promote medication adherence.

Prevalence and Associated factors of Tardive Dyskinesia among patients with schizophrenia taking Antipsychotics

1.1. Objective: Tardive dyskinesia (TD) is one of incapacitating side effect of neuroleptics. It has been implicated in the morbidity, functional impairment, stigma and overall poor prognosis of patients with schizophrenia. However, there is little information from Ethiopia. Therefore, we conducted a cross-sectional study among 161 schizophrenia patients who were admitted and on follow up at two public hospitals in Addis Ababa. We assessed TD using the Abnormal Involuntary Movement Scale. Associated factors Were also analyzed. 1.2. Results: Out of the total study participants, 41(25.5%) have TD. Clinical characteristics variables such as depot antipsychotics, combination of antipsychotics, Chlorpromazine equivalent dose of 400 mg or more and substance use were significantly associated with TD (P – value < 0.05). Nearly half of those with TD had moderate to severe TD which has significant negative impact on their day-to-day activities. 1.3. Conclusion: Prevalence of TD among schizophrenia patients taking antipsychotics is high. Root of administration and higher dose of antipsychotic medication and substance use were found to be factors associated. Rational use of antipsychotics and regular screening for TD for patients who takes antipsychotics is recommended.

Prevalence of Tardive Dyskinesia in an Electronic Medical Record Study at a Large Community Mental Health Treatment Center.

Objective: To determine the prevalence of tardive dyskinesia (TD) identified by clinicians in naturalistic data in a real-world treatment setting.Methods: Electronic medical record data were analyzed from a single large community mental health treatment center for all psychiatric provider encounters of 120,431 unique adult and child patients during a 5-year period from January 2013 through December 2017, focusing on clinician-identified TD in patients prescribed antipsychotic medication.Results: Only half of the antipsychotic-prescribed patients had Abnormal Involuntary Movement Scale (AIMS) information recorded in their medical records, and only 1% of those with AIMS data had a positive AIMS identifying TD. AIMS testing represented the largest source of all identified TD in these patients, but only one-third of the patients with a positive AIMS in the record had a clinical diagnosis of TD recorded in the prescriber's diagnostic impression list from billing code data. The clinical identification of only 1% of antipsychotic-prescribed patients with TD in this study is far below generally established TD prevalence estimates of previous research. An important methodological contributor to this discrepancy is generation of the data by treating clinicians in this study who greatly under identified TD relative to systematic research methodology.Conclusions: Given the recent availability of US Food and Drug Administration-approved pharmaceutical agents for treatment of TD, it is now more important than ever to identify and intervene in TD. Agency-wide policies and procedures can be established to ensure that TD assessments are systematically conducted with regularity and accuracy among all antipsychotic-prescribed patients.

Evaluation of Abnormal Movements among Senior Schizophrenics: A Local Study with Reference to Tardive Dyskinesia

Introduction: Tardive dyskinesia (TD) includes involuntary choreiform or athetoid movements of the jaw, lower face, tongue, and extremities, developing in association with the use of an antipsychotic medication, and may develop in about 20 to 40 percent of patients who require long-lasting hospitalization. In the present study, the prevalence of this condition has been measured among an elderly group of schizophrenic patients. Methods: One hundred and one elderly schizophrenic patients, who were hospitalized in the chronic section of a community psychiatric hospital, were selected for the present cross-sectional study. Abnormal Involuntary Movement Scale (AIMS) was employed to screen for patients with schizophrenia who also had TD. Scale for Assessment of Positive Symptoms, Scale for Assessment of Negative Symptoms, Schedule for Assessment of Insight, and Clinical Global Impressions – Severity of illness, as well, had been used as ancillary scales for evaluation of severity of general psychopathology of schizophrenia, and comparing the TD patients with the group of patients without TD, for probing the intervening parameters. Results: While abnormal movements were clear in 38.61% (n=39) of elderly schizophrenic patients, only seven of them (6.93 %) could be diagnosed as TD, based on the above-mentioned criteria. All of them were using conventional antipsychotic medications, accompanied with anticholinergic medications. Among TD patients, three cases had only abnormal facial and oral movements, one patient had atypical facial and oral movements as well as anomalous extremity movements, one patient had irregular facial and oral movements in addition to unusual trunk movements, and lastly, two patients had nonstandard extremity movements. In addition, around 71% of patients with TD were aware of their unusual movements. Between-group analysis did not show any significant difference between patients with TD and patients without TD in age, duration of illness, positive symptoms, negative symptoms, insight, and general psychopathology. Conclusion: According to the findings of the present study, the prevalence of Tardive Dyskinesia among elderly schizophrenic patients, who were using typical antipsychotic medications, is very lower than what has been indicated thus far.

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.

Antipsychotic-induced tardive dyskinesia as a serious adverse effect in the psychopharmacotherapy of schizophrenia

Schizophrenia is a socially significant disorder with a high prevalence among young and middle-aged people. Movement disorders, or extrapyramidal syndrome, are potentially reversible antipsychotic-induced adverse effects (AEs) that stigmatize patients and worsen quality of life. Tardive dyskinesia (TD) is a neurological AE in the extrapyramidal system, which is accompanied by abnormal involuntary non-rhythmic choreiform or athetoid movements (hyperkinesis) that occur during the long-term use of antipsychotics. The reversible and persistent forms of TD are identified. The article analyzes the prevalence and predictors of TD, as well as the issues of its diagnosis.

Putative role of pharmacogenetics to elucidate the mechanism of tardive dyskinesia in schizophrenia.

Identifying biomarkers which can be used as a diagnostic tool is a major objective of pharmacogenetic studies. Most mental and many neurological disorders have a compiled multifaceted nature, which may be the reason why this endeavor has hitherto not been very successful. This is also true for tardive dyskinesia (TD), an involuntary movement complication of long-term treatment with antipsychotic drugs. The observed associations of specific gene variants with the prevalence and severity of a disorder can also be applied to try to elucidate the pathogenesis of the condition. In this paper, this strategy is used by combining pharmacogenetic knowledge with theories on the possible role of a dysfunction of specific cellular elements of neostriatal parts of the (dorsal) extrapyramidal circuits: various glutamatergic terminals, medium spiny neurons, striatal interneurons and ascending monoaminergic fibers. A peculiar finding is that genetic variants which would be expected to increase the neostriatal dopamine concentration are not associated with the prevalence and severity of TD. Moreover, modifying the sensitivity to glutamatergic long-term potentiation (and excitotoxicity) shows a relationship with levodopa-induced dyskinesia, but not with TD. Contrasting this, TD is associated with genetic variants that modify vulnerability to oxidative stress. Reducing the oxidative stress burden of medium spiny neurons may also be the mechanism behind the protective influence of 5-HT2 receptor antagonists. It is probably worthwhile to discriminate between neostriatal matrix and striosomal compartments when studying the mechanism of TD and between orofacial and limb-truncal components in epidemiological studies.

Health Care Resource Utilization and Costs for Patients with Tardive Dyskinesia.

Tardive dyskinesia (TD) is an often-irreversible movement disorder affecting any part of the body. Patients experience debilitating symptoms that lower quality of life and increase mortality. Prolonged exposure to dopamine antagonists, which are frequently prescribed for psychiatric disorders as neuroleptic (antipsychotic) drugs, is a common cause of TD. The estimated prevalence of TD is 20%-50% among patients on antipsychotics, and the reported incidence of TD ranges from < 1% to 42%, depending on the antipsychotics studied. However, there are few real-world studies examining health care utilization and the economic burden of TD. To assess health care utilization and costs in a sample of patients with TD from the commercially insured and Medicare supplemental U.S. A retrospective analysis was conducted using Truven MarketScan Commercial and Medicare administrative claims data. Patients were included in the TD group if they had the first TD diagnosis (index date) between January 1, 2008, and September 30, 2014, with ≥ 1 inpatient or ≥ 2 outpatient nondiagnostic claims for TD (ICD-9-CM code 333.85). Patients without TD were randomly assigned an index date. Further inclusion criteria for all patients were ≥ 12 months of pre- and post-index medical and pharmacy continuous enrollment and no evidence of TD claims during the pre-index period. Patients with TD were directly matched to patients without TD within subgroups for schizophrenia, major depressive disorder, bipolar disorder, and other psychiatric disorders and propensity matched on other demographic and clinical factors. Descriptive statistics on the incidence of resource utilization and costs of health care were reported. Of 3,397 patients with TD, 834 met the selection criteria and were matched to 834 non-TD controls. Patients with TD generally had significantly greater utilization during the 12 months after TD diagnosis than in the 12 months before TD diagnosis. Their rates for health care utilization and costs were also substantially higher than for those without TD. During the post-TD-diagnosis time, inpatient admissions (55.5% vs. 26.1%; P < 0.001) and emergency room visits (61.5% vs. 50.6%; P < 0.001) occurred more for patients with TD than for patients without TD. Total health care costs were significantly greater for patients with TD than for those without TD ($54,656 vs. $28,777; P < 0.001). Patients diagnosed with TD demonstrate significantly higher health care utilization and costs compared with non-TD patients. This study was funded by Teva Pharmaceuticals (Petach Tikva, Israel). Truven Health Analytics, an IBM Watson Health Company, received payment from Teva Pharmaceuticals for the analysis in this study. Carroll is employed by Teva Pharmaceuticals and Irwin is employed by Truven Health Analytics, an IBM Watson Health Company.

Tardive dyskinesia among patients using antipsychotic medications in customary clinical care in the United States.

BackgroundTardive dyskinesia (TD) is a movement disorder resulting from treatment with typical and atypical antipsychotics. An estimated 16–50% of patients treated with antipsychotics have TD, but this number may be underestimated. The objectives of this study were to build an algorithm for use in electronic health records (EHRs) for the detection and characterization of TD patients, and to estimate the prevalence of TD in a population of patients exposed to antipsychotic medications.MethodsThis retrospective observational study included patients identified in the Optum EHR Database who received a new or refill prescription for an antipsychotic medication between January 2011 and December 2015 (follow-up through June 2016). TD mentions were identified in the natural language–processed clinical notes, and an algorithm was built to classify the likelihood that the mention represented documentation of a TD diagnosis as probable, possible, unlikely, or negative. The final TD population comprised a subgroup identified using this algorithm, with ≥1 probable TD mention (highly likely TD).Results164,417 patients were identified for the antipsychotic population, with1,314 comprising the final TD population. Conservatively, the estimated average annual prevalence of TD in patients receiving antipsychotics was 0.8% of the antipsychotic user population. The average annual prevalence may be as high as 1.9% per antipsychotic user per year, allowing for a more-inclusive algorithm using both probable and possible TD. Most TD patients were prescribed atypical antipsychotics (1049/1314, 79.8%). Schizophrenia (601/1314, 45.7%), and paranoid and schizophrenia‐like disorders (277/1314, 21.1%) were more prevalent in the TD population compared with the entire antipsychotic drug cohort (13,308/164,417; 8.1% and 19,359/164,417; 11.8%, respectively).ConclusionsDespite a lower TD prevalence than previously estimated and the predominant use of atypical antipsychotics, identified TD patients appear to have a substantial comorbidity burden that requires special treatment and management consideration.

A systematic review on treatment of tardive dyskinesia with valbenazine and deutetrabenazine.

Recent reports state that the prevalence of tardive dyskinesia (TD) is 32% with typical antipsychotics, and 13% with atypical antipsychotics. Current evidence-based recommendations determine an unmet need for efficacious treatment of TD. This systematic review was planned to update the evidence for TD treatment, comparing two vesicular monoamine transporter 2 (VMAT2) inhibitors, deutetrabenazine (DBZ), and valbenazine (VBZ). Of 75 PubMed search results, 11 studies met the review criteria. Efficacy and tolerability were demonstrated in a series of randomized, placebo-controlled clinical trials in our review study, and the Abnormal Involuntary Movement Scale response of ⩾50% reduction in score was robust for VBZ 80 mg/day in short-term and long-term studies. On the contrary, DBZ was equally efficacious at 12 mg twice daily, but additional information about long-term efficacy and persistence of effect is needed.

Tardive dyskinesia: Who gets it and why

Tardive dyskinesia (TD) is a potentially permanent movement disorder resulting from chronic use of dopamine receptor blocking agents (DRBA). Identified risk factors include the type of antipsychotic agent, being greater for those of first generation antipsychotics (FGA), the duration of illness and cumulative dose of DRBA and advanced age. Female sex and African and Caucasian ethnicity are additional potential risk factors. Because only a subset of people taking DRBA's develops TD, genetics may play a role. Susceptibility gene candidates include those involved in DRBA metabolism and the targets or receptors of DRBA's. Although met with conflicting data, the following genes may be involved with TD development: the cytochrome P450 gene CYP2D6, involved with metabolism of most antipsychotics, Dopamine D2 and D3 receptor genes, serotonin 2A and 2C receptor genes, vesicular monoamine transporter 2 (VMAT 2) gene, involved with intracellular neurotransmitter packaging, and the manganese superoxide dismutase (MnSOD) gene, an antioxidant enzyme. Heparan sulfate proteoglycan 2 (HSPG 2) gene is another potential gene involved with development of TD. The pathogenesis of TD is unknown, however there are three main theories proposed: dopamine receptor supersensitivity resulting from chronic dopamine receptor blockade, oxidative stress and maladaptive synaptic plasticity each of which is discussed further in this article.Tardive dyskinesia (TD) is a potentially permanent and disabling adverse effect from certain medications. By definition TD is the insidious onset of rhythmic, repetitive, stereotypic movements of the face, mouth and tongue, often with involvement of the trunk and extremities that occur as a result of dopamine receptor blocking agents (DRBA) [1]. The term tardive refers to the delayed onset of the disorder. The mean prevalence of TD is estimated to be 25.3% in psychiatric patients taking antipsychotics [2]. Compared to the number of people taking these drugs, TD represents a minority. TD is a potentially permanent condition; stopping the offending agent does not always alleviate the condition. Therefore, prevention of TD by avoiding DRBA's if at all possible is ideal. However, there is no apparent way to predict who will develop TD and there are some cases in which DRBA's are necessary for treatment of chronic conditions. As TD has been present since the development of DRBA's, possible risk factors for its development have been studied. Solmi et al. (2018) [3] have written a comprehensive review on this subject.

Antipsychotic-Related Movement Disorders: Drug-Induced Parkinsonism vs. Tardive Dyskinesia-Key Differences in Pathophysiology and Clinical Management.

IntroductionDrug-induced parkinsonism (DIP) and tardive dyskinesia (TD) are stigmatizing movement disorders associated with exposure to dopamine receptor blocking agents such as antipsychotics, but they differ in their pathophysiology and clinical management. Treatment for one may worsen the other, and there are important diagnostic clues that assist in making an accurate assessment and instituting a rational treatment plan.MethodsA literature review was executed to identify articles relating to the presentation, pathophysiology, epidemiology, and management of DIP and TD.ResultsDIP and TD prevalence estimates range from approximately 20 to 35% among antipsychotic users, but may be higher in select populations. DIP often presents as bradykinesia and rigidity, as well as rhythmic tremor, and the majority of cases appear within hours to weeks of initiation of therapy with an antipsychotic, or if dosage of the antipsychotic is increased. TD onset is delayed, typically appearing after at least 3 months or longer of treatment, and patients will commonly present with involuntary, abnormal facial movements such as lip smacking, puckering, chewing, or tongue protrusion. DIP often resolves with discontinuation of the causative agent, but TD may be permanent. Broadly, proposed mechanisms underlying these adverse events include decreased dopamine concentrations in the nigrostriatal pathway of the striatum and dopamine hypersensitivity, for DIP and TD, respectively. Pharmacologic treatment approaches for DIP have commonly included anticholinergic agents such as benztropine; however, anticholinergic medications can make TD worse. Switching the antipsychotic medication to one with lower propensity for DIP is an option for some patients. Amantadine, a non-anticholinergic agent used for the treatment of DIP, may be preferred in patients with comorbid DIP and TD. In TD, treatment options include the new reversible vesicular monoamine 2 transporter inhibitors, valbenazine and deutetrabenazine.ConclusionsIt is important for clinicians to be able to recognize DIP and TD in patients using antipsychotics so that they can minimize the impact of these adverse events on their patients’ quality of life. Accurate diagnosis will drive the selection of the correct treatment.Plain Language SummaryPlain language summary available for this article.

Tardive Dyskinesia: Recognition, Patient Assessment, and Differential Diagnosis.

Tardive dyskinesia (TD) is an involuntary movement disorder associated with antipsychotic treatment. Because of the serious and potentially irreversible nature of TD, accurate diagnosis is crucial. However, diagnosing TD can be challenging, since the subtle and often fluctuating symptoms can be easily mistaken for symptoms of mental illness or other side effects. Although the risk of developing TD in relation to treatment with second-generation antipsychotics is lower than that associated with first-generation antipsychotics, the risk still exists and may be greater than once believed. Clinicians prescribe antipsychotics for a variety of illnesses and may underestimate the possibility of a patient developing TD, thus missing early signs of the disorder. In this ACADEMIC HIGHLIGHTS, experts review the prevalence, phenomenology, risk factors, and impact of TD, illustrated by case examples, and provide valuable clinical information to guide early recognition and accurate diagnosis.

Session 205 - On the Move: An Update on Tardive Dyskinesia

Abstract: Tardive dyskinesia (TD) affects 20–50% of patients treated with antipsychotic medications. The iatrogenic nature of TD was initially unrecognized when antipsychotics were first introduced in the 1950s. However, substantial research has since been conducted to elucidate the prevalence, risk factors, possible pathophysiology, and assessment of TD. Unfortunately, TD is potentially irreversible making prevention the primary mechanism for decreasing its prevalence. Extant literature suggests differences between races and genders in rates of TD. There also appears to be a dose (mean and cumulative)-response relationship between neuroleptics and development of TD as well as an increased risk with typical versus atypical antipsychotics. Other factors potentially impacting development of TD include Major Depressive Disorder, substance use disorders, movement disorder at baseline, history of ECT, diabetes, smoking, and genetic predisposition. While there is much yet to discover, proposed underlying mechanisms for the development of TD include hypersensitivity of nigrostriatal dopamine receptors after chronic blockade by neuroleptics, impaired synaptic plasticity, neurotoxicity due to oxidative stress, and genetic mutations. Subsequently, dopamine-depleting agents, benzodiazepines, anticholinergics, and antiepileptics have been researched as possible pharmacotherapies to ameliorate TD. Thus far, the benefits of these agents have not been robust. Recently, however, the FDA has improved the first medication for treatment of TD. Valbenazine inhibits vesicular monoamine transporter type 2 (VMAT2) which decreases monoamine uptake into synaptic vesicles and depletes monoamine stores. Because of its novelty, cost can be prohibitive for some patients; however, it may provide relief for some patients for whom other treatments have thus far failed. Because of the potential long term effects of TD on patients' overall well-being, it is important for clinicians to be vigilant regarding selection of antipsychotic medication, assessment of TD and available treatments for TD.

Tardive Dyskinesia Associated with Atypical Antipsychotics: Prevalence, Mechanisms and Management Strategies.

All antipsychotics, including the atypical antipsychotics (AAPs), may cause tardive dyskinesia (TD), a potentially irreversible movement disorder, the pathophysiology of which is currently unknown. The prevention and treatment of TD remain major challenges for clinicians. We conducted a PubMed search to review the prevalence and etiology of and management strategies for TD associated with AAPs. TD prevalence rates varied substantially between studies, with an estimated prevalence of around 20% in patients using AAPs. The risk of TD is lower with AAPs than with typical antipsychotics (TAPs) but remains a problem because AAPs are increasingly being prescribed. Important risk factors associated with TD include the duration of antipsychotic use, age, and ethnicity other than Caucasian. Theories about the etiology of TD include supersensitivity of the dopamine receptors and oxidative stress, but other neurotransmitters and factors are probably involved. Studies concerning the management of TD have considerable methodological limitations. Thus, recommendations for the management of TD are based on a few trials and clinical experience, and no general guidelines for the management of TD can be established. The best management strategy remains prevention. Caution is required when prescribing antipsychotics, and regular screening is needed for early detection of TD. Other strategies may include reducing the AAP dosage, switching to clozapine, or administering vesicular monoamine transporter (VMAT)-2 inhibitors. In severe cases, local injections of botulinum toxin or deep brain stimulation may be considered. More clinical trials in larger samples are needed to gather valid information on the effect of interventions targeting TD.

MSBIS: A Multi-Step Biomedical Informatics Screening Approach for Identifying Medications that Mitigate the Risks of Metoclopramide-Induced Tardive Dyskinesia

In 2009 the U.S. Food and Drug Administration (FDA) placed a black box warning on metoclopramide (MCP) due to the increased risks and prevalence of tardive dyskinesia (TD). In this study, we developed a multi-step biomedical informatics screening (MSBIS) approach leveraging publicly available bioactivity and drug safety data to identify concomitant drugs that mitigate the risks of MCP-induced TD. MSBIS includes (1) TargetSearch (http://dxulab.org/software) bioinformatics scoring for drug anticholinergic activity using CHEMBL bioactivity data; (2) unadjusted odds ratio (UOR) scoring for indications of TD-mitigating effects using the FDA Adverse Event Reporting System (FAERS); (3) adjusted odds ratio (AOR) re-scoring by removing the effect of cofounding factors (age, gender, reporting year); (4) logistic regression (LR) coefficient scoring for confirming the best TD-mitigating drug candidates. Drugs with increasing TD protective potential and statistical significance were obtained at each screening step. Fentanyl is identified as the most promising drug against MCP-induced TD (coefficient: −2.68; p-value<0.01). The discovery is supported by clinical reports that patients fully recovered from MCP-induced TD after fentanyl-induced general anesthesia. Loperamide is identified as a potent mitigating drug against a broader range of drug-induced movement disorders through pharmacokinetic modifications. Using drug-induced TD as an example, we demonstrated that MSBIS is an efficient in silico tool for unknown drug-drug interaction detection, drug repurposing, and combination therapy design.

Epidemiology, Prevention, and Assessment of Tardive Dyskinesia and Advances in Treatment.

​​ Tardive dyskinesia (TD) is a disorder characterized by involuntary movements, typically of the orofacial muscles and also of the extremities and other muscle groups. The condition is associated with exposure to dopamine receptor blocking agents, including antipsychotics. Because the indications and off-label uses for these agents have expanded over the last 2 decades, a larger number of patients are receiving antipsychotic medications than in the past. While evidence suggests that patients being treated with second-generation antipsychotics have less risk for developing TD than those treated with first-generation antipsychotics, the decreased risk is not as great as was originally expected. In addition, patients with chronic psychiatric conditions often require long-term use of antipsychotics, putting them at risk for TD. This article addresses the prevalence, risk factors, and prevention of TD; assessment strategies including diagnostic criteria and rating scales; and evidence for TD treatments, including 2 newly approved medications: deutetrabenazine and valbenazine. ​​​.

Valbenazine for the treatment of tardive dyskinesia

ABSTRACTIntroduction: Tardive dyskinesia (TD) is a hyperkinetic movement disorder that may result from treatment with antipsychotics or other dopamine receptor blocking agents. Underlying pathophysiology is incompletely understood but since the 1970s dopamine depleting agents have been used to reduce involuntary movements. The search for safe, effective treatments for TD is ongoing. Valbenazine, a novel VMAT2 inhibitor, has recently been FDA approved for treatment of TD.Areas covered: An overview of TD, unmet medical needs and current treatment guidelines are presented. The background, chemistry and clinical development of valbenazine to treat TD is detailed. A competitive market is developing as the treatment gap is identified and potential therapies are discussed in context of a broader market overview.Expert opinion: Antipsychotic use is growing among adults and children in the U.S. Consequently, prevalence of TD is expected to rise. Cessation of antipsychotics is often not possible as the psychiatric condition may deteriorate. Increasing doses of an antipsychotic to suppress involuntary movements is not sustainable long term as underlying TD worsens and movements typically recur. There were no FDA approved treatments for TD. The approval of valbenazine to treat TD is a critical step in addressing this gap in neurologic care.

Tardive Dyskinesia Prevalence in the Period of Second-Generation Antipsychotic Use: A Meta-Analysis.

Comparison of tardive dyskinesia (TD) prevalence during contemporaneous treatment with first-generation antipsychotics (FGAs) and/or second-generation antipsychotics (SGAs). PubMed/MEDLINE/Google Scholar search (January 1, 2000-September 30, 2015) without language restriction using (tardive dyskinesia OR tardive) AND (antipsychotic*) plus specific names of SGAs. Of 8,895 hits, we screened 203 full-text articles for cross-sectional, rating scale-based TD rates during SGA, FGA, or FGA+SGA treatment. Forty-one studies were used for random effects meta-analysis and meta-regression. Two authors independently extracted data on overall and antipsychotic class-wise TD rates and on TD moderators. The global mean TD prevalence was 25.3% (95% CI = 22.7%-28.1%) across all 41 studies (N = 11,493, mean age = 42.8 years, male = 66.4%, schizophrenia-spectrum disorders = 77.1%). TD prevalence varied greatly: Rates were lower with current SGA treatment (20.7%; 95% CI = 16.6%-25.4%, N = 5,103) vs current FGA treatment (30.0%; 95% CI = 26.4%-33.8%, N = 5,062; Q = 9.17, P = .002). This difference remained significant after controlling for moderators: higher age (Z = 2.85, P = .004; number of studies = 39 ) and region (39 studies; Asia vs Europe, Z = 1.55, P = .12; Asia lower than United States, Z = 2.6, P = .009; Asia lower than other regions, Z = 2.42, P = .015). Additional moderators of TD prevalence included longer illness duration (R² = 0.15; P = .03; 21 studies) and frequency of parkinsonism (R² = 0.23, P = .017; number of studies = 19). Particularly low TD prevalence (7.2%; number of studies = 4) was found in the treatment arms with FGA-naive subjects relative to SGA-treated cohorts with likely prior FGA exposure (23.4%; P < .001; 28 studies). Lower TD prevalence of SGA relative to FGA was also confirmed in the subgroup of studies reporting on ≥ 2 antipsychotic classes/combinations; this was found for both SGAs vs FGAs (risk ratio = 0.80; 95% CI = 0.67-0.95, Z = -2.55, P = .011) and FGA + SGA vs FGAs (risk ratio = 0.80, 95% CI = 0.71-0.90, Z = -3.56, P < .001). Reports on TD severity, provided by 10 studies, were of insufficient quality for meta-analysis. Rating scale-based TD remains highly prevalent, with higher rates during FGA than during SGA treatment. However, TD severity was insufficiently reported to allow for interpretation of the clinical impact of identified TD cases with SGAs and FGAs. Reasons for high geographical variation warrant future research.

Uzun süreli ve yatırılarak izlenen şizofreni hastalarında tardiv diskinezi

Objective: Tardive dyskinesia (TD) is a group of delayed-onset iatrogenic movement disorders caused by dopamine receptor-blocking agents. TD prevalence is estimated as 20-50% of all patients treated with neuroleptics. This study aimed to investigate the prevalence rate of TD in long-term hospitalized patients with schizophrenia. Method: We recorded age, gender, duration and type (first/second generation or mixed) of medication both at the time of interview and over preceding years. Dyskinesia was assessed by using the Abnormal Involuntary Movements Scale (AIMS). We also used the Simpson–Angus Scale for tardive parkinsonism. Akathisia was measured using the Barnes Akathisia Rating Scale (BARS). Results: Mean duration of the longest used antipsychotic was 206.63 months. Probable TD was found in 18 (22.5%) of patients. None of the patients had tardive akathisia. Relation between type of the longest used treatment and prevalence of TD was not statistically significant. Relationship between type of ongoing treatment and prevalence of TD was not determined statistically significant either. There was a statistically significant relationship between the mean age and TD. Discussion: Despite very long duration of antipsychotic use, 22.5% rate of prevalence is still lower than expected. This can be explained that these patients are under direct and close follow-up of healthcare providers and in hospital conditions, so that risky conditions can be intervened rapidly. Another noteworthy finding of our study is that there is no statistically significant difference betwen first and second generation antipsychotic use and TD prevalence.