Drug-induced Tardive Dyskinesia Research Articles

Drug-Induced Tardive Dyskinesia

Drug-induced movement disorders could be classified into acute, subacute, and chronic based on the time of occurrence. Tardive dyskinesia (TD) is one of the most frequent long-term drug-induced movement disorders. Delay in treatment often caused TD to be irreversible. In this review, we will discuss TD in-depth to enhance clinician knowledge regarding the diagnosis, prevention, and comprehensive management of patients with TD. Keywords: tardive dyskinesia, movement, disorder, antipsychotic.

Candidate genes involved in the development of antipsychotic-induced tardive dyskinesia in patients with schizophrenia

Introduction. Drug-induced dyskinesia is an iatrogenic undesirable side reaction from the extrapyramidal system that occurs during the administration of drugs, most often antipsychotics in patients with schizophrenia. At the end of the 20 th century, studies were conducted on the search for candidate genes and the carriage of single nucleotide variants of antipsychotics-induced tardive dyskinesia. Purpose of the study – to analyze research results reflecting candidate genes and their single nucleotide variants associated with antipsychotic-induced tardive dyskinesia. Materials and methods. We searched for full-text publications in Russian and English in the eLIBRARY, PubMed, Web of Science, Springer databases using keywords (tardive dyskinesia, drug-induced tardive dyskinesia, antipsychotics, antipsychotics, typical antipsychotics, atypical antipsychotics, genes, polymorphisms) and combined searches for words over the past decade. Results. The lecture discusses candidate genes encoding proteins/enzymes involved in the pharmacodynamics and pharmacokinetics of antipsychotics Conclusion. Timely identification of individual genetic characteristics of the patient can contribute to the development of diagnostic test systems and in the future selection of the safest and most effective antipsychotic therapy.

Psychotropic Medications-Induced Tardive Dyskinesia and Associated Factors Among Patients with Mental Illness in Ethiopia.

BackgroundTardive dyskinesia (TD) remains a significant burden especially among patients taking psychotropic medications, and it is associated with adverse effects that can lead to subjective suffering, stigma, poor compliance to medication, and poor quality of life. However, it is unrecognized and overlooked in clinical settings. So, this study aimed to assess the magnitude of tardive dyskinesia and associated factors among mentally ill patients attending follow-up treatment at Jimma University Medical Center Psychiatry clinic, Jimma, Southwest Ethiopia, 2019.MethodsInstitutional-based cross-sectional study design was conducted in 417 samples. Participants were selected by systematic random sampling techniques. Data were collected by a semi-structured interviewer-administered questionnaire, and the document was reviewed to obtain the patient’s profile. Tardive dyskinesia was assessed by using the Extrapyramidal Symptom Rating Scale after informed consent was obtained from respondents. Data entry was done by EpiData version 3.1, and analysis was done by using SPSS 22.0 statistical software. Binary logistic regression and multivariate logistic regression were used to see the association and to identify independent factors at a p-value of <0.05.ResultsPrevalence of drug-induced tardive dyskinesia was 15.4% (CI 95%: 12.0, 19.3). Female, age range between 30 and 44 years, having a diagnosis of major depressive disorder with the psychotic feature, taking chlorpromazine equivalent dose ˃600mg, and taking anticholinergic medications were variables positively associated with tardive dyskinesia, whereas cigarette smoking was negatively associated with tardive dyskinesia.ConclusionThe prevalence of drug-induced tardive dyskinesia in this study was high. Prescribing medications less than 600mg equivalent dose of chlorpromazine, giving attention for female patients, patients having a diagnosis of major depressive disorder, and reducing giving anticholinergic medications will be important measures for clinicians to reduce the occurrence of tardive dyskinesia.

Drug-Induced Movement Disorders and Its Associated Factors Among Patients Attending Treatment at Public Hospitals in Eastern Ethiopia.

BackgroundAntipsychotic medications have both beneficial and undesired effects at a dose used for treatment purposes. Among undesired effects caused by antipsychotics, movement disorders are prevalent. However, there is no study done to determine the prevalence of movement disorders that occurred due to antipsychotics and their determinants in eastern Ethiopia.ObjectiveThis study aimed to find out the prevalence of drug-induced movement disorders and its determinants among patients who had been on follow-up at public hospitals in eastern Ethiopia.MethodsA cross-sectional study was conducted from May to June 2018 at HFSUH and Jugal hospital. Extrapyramidal symptom rating scale (ESRS) was used to identify patients with drug-induced movement disorders in a sample of 411 outpatients. A systematic random sampling method was used to select the sample. Logistic regression was done to identify factors associated.ResultsA drug-induced movement disorder was found in 44% of the participants: Of this, 27.3% had drug-induced pseudo-Parkinsonism, 21.2% had drug-induced akathisia, 9.5% had drug-induced tardive dyskinesia, and 3.4% had drug-induced tardive dystonia. Being female was associated with pseudo-Parkinsonism (AOR=3.6, 95% CI: 2.03, 6.35), akathisia (AOR=4.9, 95% CI: 2.73, 8.78), and tardive dyskinesia (AOR=2.51, 95% CI: 1.08, 5.86) and being male with tardive dystonia (AOR=4.6, 95% CI: 1.8, 18.5). Alcohol use was associated with tardive dyskinesia (AOR= 5.89, 95% CI: 2.20, 15.69).ConclusionDrug-induced movement disorder in this study was high and nearly half of patients on antipsychotic treatment were experiencing it. Age, sex, and doses of antipsychotics were factors associated with all of the types of drug-induced movement disorders.

Drug-induced dyskinesias, can they be prevented?

Abstract Introduction: Dyskinesia is a symptom complex in the form of involuntary, repetitive movements of lips, lower jaw, tongue, less often the trunk and limbs. Despite the use of newer drugs in treatment neuroleptics, dyskinesia has not ceased to be a clinical problem. Method: The work is based on a research review for which the Google Scholar database was used as well PubMed. The search range was limited to 2008-2020. We have included descriptive publications tardive dyskinesia only as a consequence of antipsychotic medications. Material: We present the use of tetrabenazine analogues, deep brain stimulation, neuroleptics, benzodiazepines and botulinum toxin in late-suffering patients drug-induced dyskinesias, which may indicate an improvement in your health. Discussion: The first method of treating tardive dyskinesia are withdrawal antipsychotic medications, but for many patients this is impossible. Valbenazine and Deep Brain Stimulation are the most effective in treating Tardive Dyskinesia. Conclusions: There are not enough studies with the highest reliability to create unequivocal recommendations in the treatment of drug-induced tardive dyskinesia.

Pathophysiological mechanisms underlying antipsychotic-induced tardive dyskinesia

Purpose.To analyze the results of classical and modern studies reflecting the pathophysiological mechanisms of antipsychotic-induced tardive dyskinesia.Materials and methods. We searched for full-text publications in Russian and English in the databases of E-Library, PubMed, Web of Science and Springer published over the past decade, using keywords (tardive dyskinesia (TD), drug-induced tardive dyskinesia, antipsychotics (AP), neuroleptics, typical antipsychotics, atypical antipsychotics, pathophysiology, etiology and combinations of these words). In addition, the review included earlier publications of historical interest.Results. The lecture proposed theories of development of AP-induced TD, examining its effect on dopaminergic receptors, dopaminergic neurons, neurons of the basal ganglia, and other theories: activation of estrogen receptors, disorders of melatonin metabolism, disorders of the endogenous opioid system, oxidative stress with predominant oxidation processes, blockade of 5-HT2-receptors, a decrease in the pyridoxine level, genetic predisposition, interaction of AP with the brain trace element – iron, carbonyl stress and immune inflammation and the role of the neurotrophic factor.Conclusion. The disclosure of the mechanisms of AP-induced TD will allow the development of a strategy for personalized prevention and therapy of the considered neurological complication of the AP-therapy for schizophrenia in real clinical practice.

Minimize exposure to antidopaminergic drugs whenever possible to reduce the risk of drug-induced parkinsonism and tardive dyskinesia

Minimize exposure to antidopaminergic drugs whenever possible to reduce the risk of drug-induced parkinsonism and tardive dyskinesia

A Study on Drug-Induced Tardive Dyskinesia: Orofacial Musculature Involvement and Patient’s Awareness

Schizophrenia is a psychiatric disorder that requires long-term treatment. Long-term antipsychotic treatment is often associated with the emergence of tardive dyskinesia (TD), the severity of which is measured by Abnormal Involuntary Movement Scale (AIMS). This study examined the relationship among TD, orofacial musculature activity, and patient's awareness of AIM. The knowledge would help dentists to deliver oral care for schizophrenics with TD. We identified 317 patients from a standard, data sharing initiative, of whom 38.3% exhibited AIM score of 2 to 15. The patient demographics, drug history, details of AIMS were subjected to descriptive and inferential statistical analysis using SPSS with P≤0.05 as significance. The mean of only orofacial features (n = 56) was 3.43 ± 2.68. Muscles of facial expression was involved in nine (7.9% of all TD), lip/perioral area in 27 (23.68%), jaw in 52 (45.61%), and tongue in 77 (67.54%). The patient's perception of AIM precipitated stress when involving jaw, tongue, limbs, and trunk was statistically significant (P≤0.05). The multiple regression model statistically significantly predicted TD for factors considered. Around 1% of global population is being diagnosed with schizophrenia, carry an inherent risk of developing TD. They might have orodental care requirements, including prosthodontic and restorative services. Primary physicians and dentists need to be aware of TD and its mechanism for appropriate patient management.

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.

Protective effect of hesperetin against haloperidol-induced orofacial dyskinesia and catalepsy in rats

Objectives: The present study was designed to evaluate the effect of hesperetin on haloperidol-induced orofacial dyskinesia and catalepsy in Wistar male albino rats.Methods: Haloperidol (1 mg/kg, ip) was administered for 21 successive days to induce orofacial dyskinesia and catalepsy. Hesperetin (50 and 100 mg/kg, po) was administered 10 min prior to the injection of haloperidol for 21 successive days. Vacuous chewing movements (VCMs), tongue protrusions, catalepsy, and locomotor activity scores were recorded on 7th, 14th, and 22nd day of drug treatment. After behavioral testing, animals were sacrificed and various biochemical parameters such as brain levels of dopamine, serotonin, malondialdehyde, and reduced glutathione (GSH); and superoxide dismutase (SOD) and catalase activities were estimated.Results: Chronic administration of haloperidol significantly increased VCMs, tongue protrusions, and catalepsy in rats. It also produced hypolocomotion in rats. Hesperetin significantly inhibited haloperidol-induced VCMs, tongue protrusions, and catalepsy. Haloperidol significantly increased brain levels of malondialdehyde, decreased brain GSH, SOD, and catalase activities; and also decreased brain dopamine and serotonin levels. Hesperetin significantly reversed haloperidol-induced increase in brain oxidative stress and decrease in brain dopamine and serotonin levels.Discussion: Hesperetin significantly ameliorated haloperidol-induced orofacial dyskinesia and catalepsy possibly through alleviation of oxidative stress and increase in brain dopamine and serotonin levels. Thus, hesperetin may be explored further as a possible therapeutic agent for clinical management of neuroleptic drug-induced tardive dyskinesia.

The use of tetrabenazine for the treatment of drug-induced tardive dyskinesia – report of four cases

Tardive dyskinesias are defined as a syndrome of involuntary, irregular, hyperkinetic movement disorders, including mixed movement disorders of the face and the mouth as well as choreoathetoid movements of the trunk and limbs. They are a serious and usually irreversible side effect of chronic neuroleptic treatment and affect approximately 15–20% of patients. Treatment attempts using amantadine, levetiracetam, piracetam, clonazepam, propranolol, vitamin B6, vitamin E, ondansetron, botulinum toxin and Ginkgo biloba were made. However, in many cases the treatment efficacy has not been confirmed in long-term studies in larger groups of patients. Tetrabenazine, registered in Poland for the treatment of hyperkinetic motor disorders in the Huntington’s disease, is one of the available therapeutic options. We present the course and the effects of tetrabenazine therapy in four patients with antipsychotic-induced tardive dyskinesias. Based on the experience gained during the research program using tetrabenazine, we believe that the use of this agent should be limited to patients in a stable mental condition, with no current symptoms of depression or active psychotic symptoms. In our opinion, suicidal tendencies or thoughts and a history of neuroleptic malignant syndrome are absolute contraindications. The off-label use of tetrabenazine requires a written informed consent of the patient and careful monitoring of their mental and neurological condition.

P.3.b.032 - Gene polymorphisms of cytochrome P450, 1A2, 2D6 and drug-induced tardive dyskinesia in Russian patients with schizophrenia

Apelin is the endogenous ligand for the G-protein-coupled receptor (APJ). The localization of APJ in limbic structures suggests a potential role for apelin in emotional processes. However, the role of apelin in the regulation of stress-induced responses such as depression and memory impairment is largely unknown. In the present study, we evaluated the role of apelin-13 in the regulation of stress-induced depression and memory impairment in rats. We report that repeated intracerebroventricular injections of apelin-13 reversed behavioral despair (immobility) in the forced swim (FS) test, a model widely used for the selection of new antidepressant agents. Apelin-13 also reversed behavioral deficits (escape failure) in the learned helplessness test. The magnitude of the antiimmobility and anti-escape failure effects of apelin-13 was comparable to that of imipramine, a classic antidepressant used as a positive control. Rats exposed to FS stress showed memory performance impairment in the novel object recognition test, and this impairment was improved by apelin-13 treatment. Apelin-13 did not affect recognition memory performance in non-stressed rats. Furthermore, the pretreatment of LY294002 (PI3K inhibitors) or PD98059 (ERK1/2 inhibitor) blocked apelin-13-mediated activities in FS-stressed rats. These findings suggest that apelin-13 exerts antidepressant-like and recognition memory improving activities through activating PI3K and ERK1/2 signaling pathways in stressed rats.

Drug-induced tardive dyskinesia: A case report

IntroductionTardive dyskinesia (TD) is a serious medical condition that affects a significant proportion of patients treated with antipsychotic agents.ObjectiveTo report a patient who developed tardive dyskinesia after initiation of antipsychotic and antidepressant treatment.Case reportMiss H. is 24-year-old Tunisian woman who had been diagnosed with bipolar disorder 6 years ago. She received various drugs: olanzapine, haloperidol, amisulpride, sertraline, paroxetine, etc. On November 2013, she first complained of hand tremor and then developed severe dystonia of the trunk and chorea. A series of laboratory tests was performed after the onset of these involuntary movements. It included complete blood count, liver, renal, and thyroid function tests, blood prolactin level, blood glucose level, blood copper level and ceruloplasmin level. A brain MRI was also performed. These examinations showed no specific findings. The diagnosis of TD was presumed. The patient was first treated with amisulpride, lorazepam, avlocardyl and piracetam until May 2014. Then, amisulpride was substituted by olanzapine until August 2015. The luck of improvement led to her admission. We stopped antipsychotic treatments and prescribed her vitamin E (900 mg/day), clonazepam (6 mg/day) and vitamin B6. The follow-up led to the decline of the Abnormal Involuntary Movement Scale (AIMS) score of 7 points over 6 weeks.ConclusionTD remains a serious side effect that worsens the prognosis and affects the quality of life of patients. Cluster randomised trial should be done in order to develop practice recommendations for prevention and management of TD.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Tardive Dyskinesia, Oral Parafunction, and Implant-Supported Rehabilitation.

Oral movement disorders may lead to prosthesis and implant failure due to excessive loading. We report on an edentulous patient suffering from drug-induced tardive dyskinesia (TD) and oral parafunction (OP) rehabilitated with implant-supported screw-retained prostheses. The frequency and intensity of the movements were high, and no pharmacological intervention was possible. Moreover, the patient refused night-time splint therapy. A series of implant and prosthetic failures were experienced. Implant failures were all in the maxilla and stopped when a rigid titanium structure was placed to connect implants. Ad hoc designed studies are desirable to elucidate the mutual influence between oral movement disorders and implant-supported rehabilitation.

4 Case Reports: Dental Management of Patients with Drug Induced Tardive Dyskinesia (TD)

The literature is inundated with copious medical interactions and side effects resulting from pharmacotherapeutics. The Center for Disease Control and Prevention (CDC) has alluded to an increase in human lifespan, juxtaposition to the management of accompanying chronic diseases. This report focuses on involuntary movement of structures in the head and neck region that is associated with pharmacologic therapy, and the associated complications of dental management associated with this unique but growing patient population. Inherent in this report is a systematic review of Tardive Dyskinesia in the literature.

Pharmacovigilance for psychiatrists: An introduction.

Byline: Ravi. Rajkumar, George. Melvin Patients with psychiatric disorders are often managed with pharmacotherapy. Because of the chronic and relapsing nature of some of these disorders, most practice guidelines recommend that medications should be continued for several months or years. [sup][1],[2],[3] As a result, patients are at risk of experiencing a variety of adverse drug reactions (ADRs). At times, these ADRs can be life-threatening (such as neuroleptic malignant syndrome) [sup][4] or disabling (such as drug-induced tardive dyskinesia). [sup][5] It is important for psychiatrists to be aware of the processes involved in identifying and reporting ADRs, especially those that are new or unrecognized. These processes form the basis for the medical discipline of pharmacovigilance. Pharmacovigilance has been defined by the World Health Organization (WHO) as the science and activities related to the detection, assessment, understanding, and prevention of adverse drug effects. [sup][6] As such, pharmacovigilance is not a specialist activity: It is one that must be carried out by all those involved in caring for patients on medication, including doctors, nurses, and pharmacists. [sup][7],[8] The birth of pharmacovigilance has a close relationship to psychiatry. In the 1960s, thalidomide was widely used in several countries to treat insomnia during pregnancy - a common problem affecting many women. It was soon noticed by physicians that babies exposed to the drug in utero developed congenital malformations, and it was this tragedy - related to a drug that was marketed as a safe sedative - that was the beginning of the field of pharmacovigilance. [sup][9] This relationship has continued to the present day. In a recent review of nine major ADRs reported in Europe from 1995 to 2008, two of them involved psychotropics - seizures with bupropion, and suicidality in children taking SSRI antidepressants. [sup][10] While the latter was identified by a re-analysis of data from the pharmaceutical industry, the former was identified through physician reports. In an analysis of ADRs reported to the FDA between 1998 and 2005, many of the frequently implicated drugs were psychotropics [sup][11] - antipsychotics (clozapine, olanzapine, risperidone), antidepressants (duloxetine, sertraline, paroxetine, bupropion), mood stabilizers (carbamazepine, valproate, lamotrigine), and even anti-ADHD medication (atomoxetine). Now, as then, clinicians have a key role in identifying and reporting new or serious adverse drug effects. Why is Pharmacovigilance Important in Psychiatry? Pharmacovigilance activities are an important part of medical practice in general. A meta-analysis found that around 5% of hospitalizations in a general medical setting are due to adverse drug effects. [sup][12] A study in a general hospital in France found that 3% of new admissions were due to ADRs, and 6.6% of patients developed a significant ADR during their hospital stay. [sup][13] However, there are four reasons why this field is of special importance to psychiatrists. First, pharmacotherapy is the principal modality of management in several psychiatric disorders. Most drugs used in psychiatry are frequently associated with ADRs. Often, patients do not respond to initial drug therapy, and may require several trials of different medications. [sup][14],[15] Some patients may require a combination of various drugs - polypharmacy - which can increase the risk of adverse effects or drug interactions. [sup][16] Second, most clinical trials of psychotropics are conducted in ideal conditions - patients are selected according to stringent criteria, and comorbid medical conditions are usually excluded. These trials also tend to be short-term, lasting for a few weeks or months. By contrast, the patients we encounter in practice often have more complex presentations and comorbid medical illnesses, and they remain under our care for longer periods of time. …

Tardive dyskinesia after short-term treatment with oral metoclopramide in an adolescent

The objective of this case report is to report the development of tardive dyskinesia in an African-American adolescent male after short-term treatment with metoclopramide 10 mg orally three times daily secondary to delayed gastric emptying. The patient developed symptoms of tardive dyskinesia after 2 days of therapy with metoclopramide. Metoclopramide was discontinued and diphenhydramine 50 mg was initially administered intravenously followed with 25 mg orally every 4 hours as needed. While there are case reports of drug-induced tardive dyskinesia after intravenous administration of metoclopramide, this is to our knowledge the first report of tardive dyskinesia after short-term treatment with oral metoclopramide in an adolescent. Awareness of the risk of development of this adverse effect even with short-term treatment with metoclopramide and in younger patients is important.

Postthalamic Stroke Dystonic Choreoathetosis Responsive to Tetrabenazine

To describe the case of a woman with poststroke choreoathetosis whose symptoms improved after treatment with tetrabenazine. A 48-year-old left-handed woman developed progressive involuntary dystonic choreoathetoid movements of her arm following a cerebrovascular event. Involuntary abnormal movements (IAMs) were treated with haloperidol, but they worsened 6 months later, also involving her mouth, tongue, and perioral area. Because of the suspected occurrence of drug-induced tardive dyskinesia, treatment was switched to tetrabenazine (titration up to 100 mg/daily), with rapid remission of the involuntary abnormal movements (Abnormal Involuntary Movement Scale score switching from 20 to 1). One month later, following discontinuation of tetrabenazine, the dystonic choreoathetoid movements rapidly reappeared. Subsequent rechallenge with tetrabenazine caused remission of her symptoms. Poststroke IAMs are rare, and lesions involving the basal ganglia and/or thalamus seem to be particularly implicated in such disorders. The exact pathogenic mechanism has not been clarified; however, it has been postulated that a central dopaminergic overactivity might play an important role in the IAM occurrence. Thus, antipsychotics are the main treatment option, but they are often associated with therapeutic failure or adverse effects, including extrapyramidal symptoms and metabolic complications. Interestingly, when our patient was treated with tetrabenazine for haloperidol-induced tardive dyskinesia, she demonstrated substantial improvement in the dystonic choreoathetoid movements of her left upper limb. The improved response of this case to tetrabenazine monotherapy suggests that tetrabenazine may be a pharmacologic alternative for patients with poststroke choreoathetosis that is intolerant or unresponsive to antipsychotic agents. Further studies are needed to better define the risk versus benefit profile of tetrabenazine.

Drs. Nelson and Papakostas Reply

Drs. Nelson and Papakostas Reply

No evidence for an association between G protein β3 subunit gene C825T polymorphism and tardive dyskinesia in schizophrenia

Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic. We evaluated candidate functional polymorphism of the G protein beta3 subunit (GNB3) gene for association with drug-induced TD in the Korean schizophrenic patients. We investigated whether the C825T polymorphism of the GNB3 gene is associated with the TD in a Korean sample of schizophrenic patients with (n = 83) and without TD (n = 126), matched for antipsychotic drug exposure and other relevant variables. The distribution of genotypes and allele frequencies of GNB3 were not different between schizophrenic patients with TD and without TD (p > 0.05). Within the limitations imposed by the size of the clinical sample, these findings suggest that the GNB3 825 C/T single nucleotide polymorphism (SNP) does not contribute significantly to risk for TD.