Article

Glazer WM, Morgenstern H, Doucette JT. Predicting the long-term risk of tardive dyskinesia in outpatients maintained on neuroleptic medications. J Clin Psychiatry 54: 133-139

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Abstract

Tardive dyskinesia (TD) has been a source of great concern to the psychiatric community because of the iatrogenic nature of the illness. Little is known about the risk of developing TD if neuroleptic medications are continued. This paper presents long-term risk estimates for TD in a prospective cohort study of 362 chronic psychiatric outpatients who were free of TD at baseline and who were maintained on neuroleptic medications. On the basis of 5 years of follow-up, we estimate the risk of persistent TD to be 32% after 5 years of neuroleptic exposure (95% confidence interval [CI] = 23%-43%), 57% after 15 years of exposure (95% CI = 47%-66%), and 68% after 25 years of exposure (95% CI = 58%-77%). For patients with 10 years of previous neuroleptic exposure, the risk is 15% after 5 more years of exposure (95% CI = 7.2%-27%) and 38% after 15 more years of exposure (95% CI = 24%-53%). Our results fall within the wide range of results found in other studies of TD incidence. Differences in incidence across studies may be explained in terms of patient characteristics and other methodological factors. One implication of this finding is that patients in the first 5 years of exposure could be targeted for prevention programs if resources are limited. A potential methodological problem encountered when studying chronically exposed patients is that they may have acquired TD (persistent) prior to the study and remitted before entry.

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... Several sets of diagnostic criteria incorporate severity thresholds for diagnosis of TD based on AIMS scores. 11,12 These scores are principally used to estimate the prevalence or incidence of TD and to qualify and monitor patients entered into clinical trials. However, a more definitive clinical diagnosis of TD requires a history of treatment with antipsychotics, duration of abnormal movements, and a more informed analysis of symptomology and differential diagnosis. ...
... However, nearly two-thirds or more of patients with TD were not captured by a range of diagnostic criteria based on AIMS severity scores, including criteria generally accepted as standard across virtually all research studies. 11,12 Under circumstances of nonadherence with regular screening and apparent limited sensitivity and reliability of recorded scores, use of the AIMS in screening for TD may not improve the chances of diagnosing TD. The highest sensitivity was observed with a threshold of any one item rated at least mild, but even that captured only 37.1% of cases of TD, and identified 6.4% of patients without diagnosed TD as positive. ...
Article
Purpose/background: To add to limited evidence on the Abnormal Involuntary Movement Scale (AIMS) as a measure of tardive dyskinesia (TD) in clinical practice settings, the characteristics and correlates of AIMS scores were assessed. Methods/procedures: Veterans with schizophrenia/schizoaffective, bipolar, or major depressive disorders receiving antipsychotics and at least 1 AIMS score during October 1, 2014, to September 30, 2015, were identified. Tardive dyskinesia was determined by the International Classification of Diseases, Ninth Revision, Clinical Modification, codes. Correlates of AIMS scores were examined using χ or t tests. Odds ratios and β parameters with 95% confidence intervals for categorical and continuous variables associated with AIMS scores were derived from a multivariate logistic and linear regression, respectively. Findings/results: Among 7985 veterans receiving antipsychotics, only 4706 (58.9%) had at least 1 AIMS examination. Of these, 229 (4.9%) were diagnosed with possible TD. The mean total AIMS scores and AIMS awareness/incapacitation scores were significantly higher for patients with TD (both P < 0.0001). Comparing diagnostic threshold criteria of AIMS ratings, only 17.5% to 37.1% of veterans with TD were successfully identified. Among TD patients, 21.4% had a total score of moderate-severe and 15.3% had ratings of at least mild movements in 2 or more body regions. In the regression analyses, being older, African-American, having schizophrenia/schizoaffective disorder, and receiving antipsychotics or benztropine significantly increased the severity of AIMS scores. Higher AIMS scores were not predictive of outcomes other than marital status in socioeconomic or healthcare domains. Implications/conclusions: Although the AIMS is essential for TD research, its value in clinical practice without training and oversight remains unclear. Efforts to adapt screening procedures to clinical needs may be worthwhile.
... Так, было показано, что за первые 4-5 лет лечения антипсихотиками частота дискинезий линейно возрастает вместе с длительностью терапии. Уже тогда была прослежена закономерность возрастания риска дискинезии вследствие применения высоких доз антипсихотиков и проведения ЭСТ в анамнезе [3,4]. Эти данные подтверждены другими исследователями, которые длительно наблюдали пациентов, принимающих антипсихотики. ...
... Эти данные подтверждены другими исследователями, которые длительно наблюдали пациентов, принимающих антипсихотики. В этих работах было показано, что двигательные побочные явления возникали у четверти больных спустя 5 лет от начала приема антипсихотиков, а к 10 годам лечения нарушения отмечались почти у половины обследуемых (49%) и к 25 годам составляли уже 68% [3][4][5]. ...
... However, the importance of presynaptic D2 receptors has not been adequately addressed in previous publications. Tardive dyskinesia is often a slow onset movement disorder, occurring in 68% of patients who have taken chronic antipsychotics for approximately 25 years, with a 5% increase per year of drug use [2]. The condition usually takes months or years of antipsychotic drug use to develop. ...
... Repetitive short-term use of D2 blockers can result in cumulative damage, potentially leading to tardive dyskinesia. This cumulative effect has been observed in many patients treated with antipsychotic agents [2]. ...
Article
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It is likely that tardive dyskinsesia is caused by the oxidation of dopamine in dopaminergic neurons. This oxidation produces oxygen radicals that damage neurons. Damage accumulates until tardive dyskinesia occurs. The use of dopamine D2 receptor inhibitors should be limited to the lowest doses for the shortest duration possible.
... Three outpatients who met the following criteria were recruited; the Diagnostic and Statistical Manual of Mental Disorders 5th edition criteria for schizophrenia; diagnostic criteria for TD [29]; actively smoking based on cigarette consumption and exhaled carbon monoxide (CO); and no change in antipsychotic drugs for two months prior to screening. Approval was obtained from the Institutional Review Board at the Corporal Michael J. Crescenz VA Medical Center and written informed consent was obtained (ID #: 01730, Prom #: 0022). ...
Article
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Objectives: Although evidence implicates striatal cholinergic impairment as a mechanism underlying tardive dyskinesia, trials of nonspecific cholinergic agents have been inconclusive. As a partial agonist at specific nicotinic receptor subtypes, varenicline reduces drug-induced dyskinesias in animal models suggesting promise as a treatment for tardive dyskinesia. Methods: Three schizophrenia patients with tardive dyskinesia who were smokers underwent an open trial of varenicline. After a 2-week baseline, subjects received varenicline 1mg twice daily. Changes from baseline on the Abnormal Involuntary Movement Scale were measured after a 4-week varenicline stabilization period, and 6 weeks after the smoking quit date in one patient. Results: Varenicline had no effect on mean Abnormal Involuntary Movement Scale scores after 4 weeks. Although smoking decreased after 4 weeks on varenicline and diminished further in one patient after 10 weeks, this also appeared to have no effect on ratings of tardive dyskinesia. Conclusion: In contrast to animal models, no significant change in tardive dyskinesia occurred in response to varenicline replacement in three schizophrenia patients. Further investigations of cholinergic mechanisms in tardive dyskinesia are worthwhile as agents for specific cholinergic targets become available for treatment. In addition, treatment trials of tardive dyskinesia should control for smoking status, while patients on antipsychotics receiving nicotine replacement therapies for smoking should be studied further for changes in movement.
... Several genes that may contribute to the pathogenesis of TD have been identified, and these genes, which include DRD2, DRD3, VMAT2, HSPG2, HTR2A, HTR2C and SOD2, either participate in the metabolism of antidopaminergic medications or are involved in encoding targets of antidopaminergic medications [6]. With the use of typical neuroleptic medications, this risk increases with the length of time while exposed to a neuroleptic with a 5 year prevalence estimated to be 32%; 57% after 15 years and 68% after 25 years of exposure [7]. Atypical neuroleptic medications were initially believed to confer lower risk of TD [8]. ...
Article
Tardive dyskinesia (TD) is a bothersome and - at times, disabling - movement disorder associated with exposure to dopamine receptor antagonist medications. On 11 April 2017, valbenazine became the first US FDA-approved medication indicated for the treatment of TD. Valbenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor that decreases the abnormal movements of TD. The FDA considered valbenazine a breakthrough therapy in 2014 given its underlying mechanism and its importance in addressing an unmet need, as there were no available FDA-approved medications indicated for TD. The advantages of valbenazine include once-daily dosing and a rapid onset of effect within 2 weeks of treatment initiation.
... 32 These data were confirmed by other investigators, who found that the long-term risk of TD increased up to 25% after 5 years, 49% after 10 years, and 68% after 25 years. [33][34][35] According to some studies, the incidence rates of TD among psychiatric patients aged 55 or above were 25%, 34%, and 53% after 1, 2, and 3 years of cumulative antipsychotic treatment, respectively, 35 and 12% among outpatients over the age of 45 years. 36 Since the introduction of the second-generation (atypical) antipsychotics (SGA) to clinical practice, many papers on the incidence and prevalence of TD have been published. ...
Article
Tardive dyskinesia is a serious, disabling and potentially permanent, neurological hyperkinetic movement disorder that occurs after months or years of taking psychotropic drugs. The pathophysiology of tardive dyskinesia is complex, multifactorial and still not fully understood. A number of drugs were tried for the management of this motor disturbance, yet until now no effective and standard treatment has been found. It is very disappointing to realize that the introduction of antipsychotics from the second generation has not significantly decreased the prevalence and incidence of tardive dyskinesia. Therefore, the management of this motor disturbance remains an actual topic as well as a challenge for clinicians. This review summarizes recent relevant publications concerning the treatment of tardive dyskinesia.
... TD is characterized by abnormal involuntary movements of the face and extremities, and may fluctuate in severity (86,87). In patients treated with FGAs, the incidence of TD is estimated as 5% per year (88), with a prevalence range of 20-25% among schizophrenia patients treated with antipsychotics chronically (86). SGAs are considered less likely to cause TD than FGAs, approximately 1% annually (89), but this rate is higher, according to other reports (90). ...
Article
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Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP) and tardive dyskinesia (TD). Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of motor symptoms in Parkinson's disease (PD). Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD) is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD motor sub-phenotypes, such as age at onset, disease severity, or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants could also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of l-DOPA induced dyskinesia (LID) is an additional relevant sub-phenotype. LID might share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study.
... 23, 24 These abnormalities have been reported to occur with a higher prevalence during treatment with conventional antipsychotics than with atypical antipsychotics, and their adverse impact on quality of life and treatment compliance has been documented. [24][25][26][27][28][29][30][31] In addition to treatment-related factors that may be associated with sexual dysfunction, behavioral factors such as use of caffeine, alcohol, and tobacco also are worthy of investigation. Cigarette smoking is known to occur with greater prevalence among patients with schizophrenia than among the adult population overall, and published reports indicate that this population consumes more caffeine daily 32,33 and has a higher prevalence of alcohol dependency. ...
... It has been estimated that, with FGAs, the risk of persistent TD is 32% after 5 years of exposure, 57% after 15 years of exposure, and 68% after 25 years of exposure. 35 This translates into roughly 4% to 6% risk per year of exposure, with higher rates earlier in treatment but an enormous cumulative likelihood averaging about 5% per year of exposure. Moreover, the risk appears to be related to cumulative lifetime amount of antipsychotic medication received, 36 meaning that low doses for a very long time may postpone but not eliminate the risk. ...
Article
Tardive dyskinesias (TD) are serious, often irreversible side effects of dopamine blocking agents, most commonly first-generation antipsychotics. No definitive treatment exists, with different interventions showing inconsistent results. We report a case of TD presenting after 12 years of olanzapine therapy in a 66-year-old Hispanic male with paranoid schizophrenia. The TD symptoms were successfully treated within a few weeks by switching to clozapine. Two cases of olanzapine- induced TD treated with clozapine have previously been reported, but in those cases, the symptom onset was quicker, ranging from a few months to a few years after initiation of olanzapine therapy, and the treatment response was relatively slower. Clinicians should carefully monitor for symptoms of TD after prolonged treatment with olanzapine and other antipsychotics. If otherwise indicated for psychiatric treatment, clozapine can be considered a good choice for patients with TD in preventing or reversing the debilitating consequences of this condition.
... The initial step in managing a patient with TD is to recognize and characterize the phenomenology of any movements by questioning patients and visual inspection, and by using standardized rating scales and diagnostic criteria [41,57,58]. A differential diagnosis and appropriate investigations should be considered, including referral to movement disorder specialists if necessary. ...
Article
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Introduction: Tardive dyskinesia (TD) occurs in patients receiving antipsychotic treatment with dopamine receptor antagonists. Despite the prevalence of TD and its negative impact on patients' lives, there has been a lack of approved treatments and limited evidence from controlled trials of pharmacological treatment. Areas covered: PubMed was searched for English-language papers published during 2007-2016 using terms "tardive dyskinesia" or "drug-induced movement disorder", and "treatment". Studies evaluating pharmacological agents for the treatment of TD were selected. A total of 26 studies (five meta-analyses, twelve randomized controlled trials, and nine open-label observational studies) are reviewed. Expert commentary: Treatment of TD necessitates a stepwise approach. Optimization of antipsychotic therapy should be considered before initiation of antidyskinetic therapies. Data from some recent studies indicate possible improvements in TD after switching antipsychotics or with the use of amantadine, levetiracetam, piracetam, zonisamide, propranolol, vitamin B6, or certain unregulated herbal medicines; although significance of these improvements is unclear and require further investigation in randomized controlled trials. By contrast, recent evidence from Phase 3 trials of novel vesicular monoamine transporter-2 inhibitors demonstrates they could have a significant effect on TD symptom severity and suggests these agents may have the potential to transform treatment of TD in coming years.
... Prospective studies have reported annual incidence estimates of 5%, with an increased cumulative incidence with increasing duration of exposure (Kane et al., 1988). The annual risk increases to 12-25% per year in the elderly population (Glazer et al., 1993). ...
Chapter
Tardive syndromes (TS) are a group of related iatrogenic disorders characterised by persistent abnormal involuntary movements resulting from the use of dopamine receptor blocking medications, which are often used to treat psychiatric and gastrointestinal conditions. The most common of the TS is classic tardive dyskinesia, characterised by involuntary stereotypic movements in the mouth region such as lip smacking or pursing, chewing, facial grimacing and tongue movements. TS can be highly disabling, difficult to treat and have the potential to be permanent, making their prevention of paramount importance. The pathophysiological basis of the TS is poorly understood. Treatment options include oral medications, botulinum toxin injections and deep brain stimulation surgery. More research is needed to determine the best available treatment options and to identify new treatments.
... 11 In a prospective cohort study that followed 362 chronic psychiatric, TD-free outpatients for five years, the predicted risk of developing TD with typical neuroleptics increases with duration of exposure, from 32% for 5 years, 57% for 15 years, and 68% after 25 years. 12 According to the most recent meta-analysis, the annual incidence of TS is 3% in adults taking atypical antipsychotics and 7.7% in those taking typical antipsychotics. 13 The non-modifiable risk factors for TD include older age, female sex, white or African descent, genetic variants involving antipsychotic metabolism and dopamine function, longer disease duration, and preexisting mood disorders. ...
Article
Full-text available
Tardive syndrome (TS) is a group of movement disorders caused by the long-term use of dopamine receptor blocking agents. The phenotypic presentation of TS is diverse, ranging from the most well-characterized symptom of tardive dyskinesia to other symptoms, including dystonia, akathisia, myoclonus, parkinsonism, tremor, and tics. These tardive symptoms are distinct not only in their phenomenology but also in their clinical outcomes. However, our knowledge of the pathophysiology and management of TS is almost exclusively based on tardive dyskinesia. First-generation antipsychotics have a higher risk of inducing TS and have largely been replaced by second-generation antipsychotics with a lower risk of TS. However, patients with off-label use of second-generation antipsychotics are still at risk of developing TS. Thus, the management of TS remains a challenging and important issue for physicians. In this review, we update the information on the epidemiology, phenomenology, and treatment of tardive syndrome from the perspective of the specific form of tardive syndrome.
... Simple scale applied to all 7 items Additional criteria for assessing quality, frequency, and amplitude of abnormal movements 22 25 AIMS total score ≥ 3 with score ≥ 2 (mild or worse) in ≥ 1 AIMS item administered in both research and clinical settings. However, it has also been noted that the lack of detailed instruction and descriptors could be challenging for inexperienced raters and therefore contribute to high interrater variability. ...
Article
Objective: To provide an historic overview of the Abnormal Involuntary Movement Scale (AIMS) in clinical trials of tardive dyskinesia (TD), with current recommendations for analyzing and interpreting AIMS data. Participants: Seven psychiatrists and 1 neurologist were selected by the workshop sponsor based on each individual's clinical expertise and research experience. Evidence: Using PubMed entries from January 1970 to August 2017, participants selected studies that used the AIMS to evaluate TD treatments. The selections were intended to be representative rather than prescriptive or exhaustive, and no specific recommendations for TD treatment are implied. Consensus process: The Working Group met in October 2016 to discuss the AIMS as an assessment tool, outline the challenges of translating clinical trial results into everyday clinical practice, and propose different methods for reporting AIMS data in clinically relevant terms. Recommendations for selecting TD studies for review, analyzing and interpreting AIMS data, and synthesizing discussions among the participants were initiated during the onsite workshop and continued remotely throughout development of this report. Disagreements were resolved via group e-mails and teleconferences. Consensus was based on final approval of this report by all workshop participants. Conclusions: For both research and clinical practice, the AIMS is a valid measure for assessing TD and the effects of treatment, but alternative analyses of AIMS data (eg, effect size, minimal clinically important difference, response analyses, category shifts) may provide broader evidence of clinical effectiveness. No single analysis of AIMS data can be considered the standard of clinical efficacy; multiple analytic approaches are recommended.
... Three investigators (WWR, LNZ, JWZ) independently reviewed ti- tles and abstracts, followed by the full review of the texts. Full texts of four papers (Czernuszenko, 2007;Glazer et al., 1993;Herve et al., 1984;Vieweg et al., 1993) were not accessible, therefore were not in- cluded in the analyses. The eligibility of studies was independently examined by two investigators (LNZ, JWZ). ...
Article
Falls are common in older adults with psychiatric disorders, but the epidemiological findings have been inconsistent. This meta-analysis examined the prevalence of falls in older psychiatric patients and its moderating factors. PubMed, EMBASE, Web of Science and PsycINFO databases were independently searched by three investigators from their inception date to Nov 31, 2017. The random effects meta-analysis was used to synthesize the prevalence of falls, while meta-regression and subgroup analyses were conducted to explore the moderating factors. Sixteen of the 2061 potentially relevant papers met the entry criteria for the meta-analysis. The pooled lifetime prevalence of falls was 17.25% (95% confidence interval: 13.14%–21.35%). Neither univariate and nor multivariate meta-regression analyses revealed any moderating effects of the study region, duration, sample size, and quality on the prevalence of falls (P values > 0.05). Falls in older adults with psychiatric disorders are common.
... Tardive dyskinesia refers to involuntary, repetitive hyperkinetic movements, including grimacing, sticking out the tongue, or smacking of the lips resulting from long-term use (-5 years: 31.8%, -10 years: 49.4%, -15 years: 56.7%, -20 years: 64.7%, 25-years: 68.4%) of FGAs or aripiprazole (SGA) because of supersensitivity in the nigrostriatal pathway [20]. ...
Article
Full-text available
Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak D2 receptor bindings with strong binding to the 5-HT2A receptor, while typical antipsychotics block long-lasting, tight D2 receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.
... Наиболее инвалидизирующими из них являются ПД [Shamir E. et al, 2001]. Приводятся данные, что ПД диагностируется у 3-5% пациентов, получавших АП в течение первых 5 лет и у 68% пациентов через 20-25 лет на фоне постоянного приёма АП [Glazer W.M. et al, 1993;Jeste D.V., 1999;2004]. Введение в практику ААП снизило риски развития ПД, но не свело их к нулю. ...
Article
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Purpose. To study and summarize the existing evidence base for the use of melatonin as a mean to counteract or diminish the side effects of various psychotropic drugs and electroconvulsive therapy, and to provide the reader with relevant conclusions. Methodology. The authors have searched for the scientific literature regarding the use of melatonin as a mean to counteract or diminish the side effects of various psychotropic drugs and electroconvulsive therapy, using the PubMed and Google Scholar as a search tool. Then the authors thoroughly reviewed the data they found. The resulting review is presented in this article. Results. The data we have obtained from this review of the literature indicate that melatonin can be effectively used both in monotherapy and in combination with other therapeutic means in order to reduce several different side effects of psychotropic drugs and electroconvulsive therapy. Melatonin also deserves further study in this regard. The evidence base for its use in this manner is very variable in quality for different side effects. For now, the greatest evidence base exists regarding the potential effectiveness of melatonin in the prevention and treatment of drug-induced insomnia, memory and cognitive impairment, akathisia, tardive dyskinesias, and metabolic syndrome. Practical implications. The results we have obtained can be widely applied in psychiatry, neurology and addiction medicine, as well as in all those areas of general medicine, which make use of psychotropic drugs.
... 56 A modification suggested by Glazer et al, which required only a total score of three with at least one body area rated as mild, offered a lower threshold but never gained currency in research studies. 64 However, observation of even mild movements in one body area (ie, an AIMS score of 2) in a clinical practice setting may be significant and sufficient for the diagnosis of TD. For example, patients who become aware of and embarrassed by mild lip-smacking cannot ...
Article
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Stanley N Caroff Corporal Michael J Crescenz VA Medical Center, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Abstract: Tardive dyskinesia (TD) is a heterogeneous syndrome of involuntary hyperkinetic movements that is often persistent and occurs belatedly during treatment with antipsychotics. Recent approval of two dopamine-depleting analogs of tetrabenazine based on randomized controlled trials offers an evidence-based therapeutic approach to TD for the first time. These agents are optimally used within the context of a comprehensive approach to patient management that includes a practical screening and monitoring program, sensitive and specific criteria for the diagnosis of TD, awareness of the severity and impact of the disorder, informed discussions with patients and caregivers, and a rational basis for prescribing decisions about continued antipsychotic and adjunctive agents. Areas of limited or inconclusive data, bias and misunderstandings about key aspects, and neglect of training about TD in recent years contribute to barriers in providing effective care and promoting patient safety. Keywords: tardive dyskinesia, valbenazine, deutetrabenazine, tetrabenazine vesicular monoamine transporter inhibitors, antipsychotics, schizophrenia, bipolar disorder, major depressive disorder, drug-induced movement disorders
... Tardive dyskinesia refers to involuntary, repetitive hyperkinetic movements, including grimacing, sticking out the tongue, or smacking of the lips resulting from long-term use (-5 years: 31.8%, -10 years: 49.4%, -15 years: 56.7%, -20 years: 64.7%, 25-years: 68.4%) of FGAs or aripiprazole (SGA) because of supersensitivity in the nigrostriatal pathway [20]. ...
Article
Background:: Tardive dyskinesia is a movement disorder characterised by irregular, stereotyped, and choreiform movements associated with the use of antipsychotic medication. We aim to provide recommendations on the treatment of tardive dyskinesia. Methods:: We performed a systematic review of studies of the treatment of tardive dyskinesia. Studies were rated for methodological quality using the American Academy of Neurology Risk of Bias Classification system. Overall level of evidence classifications and grades of recommendation were made using the Scottish Intercollegiate Guidelines Network framework. Results:: Preventing tardive dyskinesia is of primary importance, and clinicians should follow best practice for prescribing antipsychotic medication, including limiting the prescription for specific indications, using the minimum effective dose, and minimising the duration of therapy. The first-line management of tardive dyskinesia is the withdrawal of antipsychotic medication if clinically feasible. Yet, for many patients with serious mental illness, the discontinuation of antipsychotics is not possible due to disease relapse. Switching from a first-generation to a second-generation antipsychotic with a lower D2 affinity, such as clozapine or quetiapine, may be effective in reducing tardive dyskinesia symptoms. The strongest evidence for a suitable co-intervention to treat tardive dyskinesia comes from tests with the new VMAT inhibitors, deutetrabenazine and valbenazine. These medications have not been approved for use in Canada. Conclusion:: Data on tardive dyskinesia treatment are limited, and the best management strategy remains prevention. More long-term safety and efficacy data are needed for deutetrabenazine and valbenazine, and their routine availability to patients outside of the USA remains in question.
Article
Tardive dyskinesia (TD) is a serious, disabling and potentially permanent, neurological hyperkinetic movement disorder that occurs after months or years of taking dopamine receptor-blocking agents. The pathophysiology of TD is complex, multifactorial and still not fully understood. Although there is no identified effective and standard treatment for TD, several agents have been tried for the management of this motor disturbance. The aim of this case series is to review the literature in regard to the identification, diagnosis and the treatment of TD with anticholinergics, anticholinergic medication withdrawal, cholinergic agents, botulinum toxin intramuscular injections, tetrabenazine, levetiracetam, propranolol and zolpidem, and to describe one case of TD that responded favorably to clonazepam and two cases of TD that responded favorably to Ginkgo biloba.
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This article reviews pharrmacological treatment of schizophrenia from choice of an antipsychotic drug in different stages of the illness to some practical issues of maintenance treatment. Currently available medications for schizophrenia are not effective for all patients. There is a large range of clinical efficacy and individual adverse effect profiles of drugs. The personalised treatment plan needs consider not only symptoms of illness and adverse effects profile of chosen drug but also comorbid conditions, past therapeutic response and patients preferences and expectations. Clozapin, despite its side effect limitations remains the solution for treatment-refractory patients. Depot antipsychotics increase the adherence and awareness of when a patient stopped the treatment. Electroconvulsive treatment is recommended as a last resort for treatment resistant patients and as a special indication for severe catatonia.
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Introduction: The treatment of schizophrenia was revolutionized by the introduction of first-generation antipsychotics (FGAs) in the 1950s. FGAs have now been largely replaced by second-generation antipsychotics (SGAs), which have a lower propensity for acute extrapyramidal symptoms (EPS)[1,2] and perhaps tardive dyskinesia (TD).[3] There remains a need however to be able to accurately detect and manage motoric side effects of antipsychotics as these problems persist in clinical practice. Conclusion: Tardive dyskinesia rates appear to be lower with newer antipsychotic agents but still a problematic side effect that requires astute clinical skills for detection and mitigation. This chapter will review all aspects of this side effect to aid clinicians' ability to provide safe patient care while prescribing second generation antipsychotics.
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Introduction: Knowledge of morphological variations of the suprascapular region is important in the management of entrapment neuropathy and interventional procedures. The objective of this study was to collect data on the morphological features and dimensions of ossified ligaments and unusual bony tunnels of scapulae from a North Indian population. Methods: A total of 268 adult human scapulae of unknown gender were obtained from the bone bank of the Department of Anatomy, Dayanand Medical College and Hospital, Ludhiana, Punjab, India. The scapulae were evaluated for the incidence of ossified superior transverse scapular ligaments (STSLs), ossified inferior transverse scapular ligaments (ITSLs) and bony tunnels (i.e. the bony canal between the suprascapular notch and spinoglenoid notch), found along the course of the suprascapular nerve (SSN). The dimensions of these structures were measured and noted down. Ossified STSLs were classified based on their shape (i.e. fan- or band-shaped) and the dimensions of the ossified suprascapular openings (SSOs) were measured. Results: Ossified STSLs were present in 26 (9.7%) scapulae. Among the 26 scapulae, 16 (61.5%) were fan-shaped (mean area of SSO 16.6 mm(2)) and 10 (38.5%) were band-shaped (mean area of SSO 34.2 mm(2)). Bony tunnels were observed in 2 (0.75%) specimens, while an ossified ITSL was observed in 1 (0.37%) specimen. Conclusion: The data obtained in the present study augments the reference literature for SSN decompression and the existing anatomical databases, especially those on Indian populations. This data is useful to clinicians, radiologists and orthopaedic surgeons.
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Schizophrenia is a debilitating psychiatric illness that is among the world's top 10 causes of long-term disability, affecting people who are just entering the peak of social, economic, and intellectual productivity. Such functional loss is particularly relevant in indigenous communities, which rely on change in functional status (rather than on the presence of symptoms) to identify mental illness. Particularly among the indigenous communities of Latin America, the gap between mental health need and availability of resources to reduce the burden has been judged " a case of outrageous exclusion. " For more than a decade, as part of the Investigation of Movement Abnormalities and Genetic of Schizophrenia study, the authors have been studying vulnerability markers (genetic, motor, imaging, and neuropsychological differences) for schizophrenia in a remote, indigenous population in rural northern Argentina. In this article, the authors discuss the implementation of a task-shifting paradigm resulting in more proficient identification and referral of individuals with untreated psychosis and a severalfold reduction in the duration of untreated psychosis, with very high retention rates (70%) and treatment adherence during a decade in a rural environment. The authors also propose to use transcranial ultrasound screening and testing for parkin-sonism at illness onset before introduction of neuroleptics as potentially useful markers in determining illness severity, negative symptomatology, and tolerance to antipsychotic treatment/refractoriness.
Article
This case report highlights the implication of the concept of "geste antagoniste" in conservatively managing oromotor dysfunction and its complications. A 66-year-old female with a 1-year history of tardive dyskinesia (TD) was referred to the Craniofacial Pain Department (CPC) at Tufts University School of Dental Medicine for management of sore labial/lingual mucosa secondary to excessive daytime involuntary activity of the tongue, lips, and mandible. A detailed head/neck examination revealed excessive involuntary movements of the tongue, lips, and mandible with generalized tenderness of her masticatory muscles. No TMJ or bone pathology was evident in a panoramic radiograph. A lower daytime appliance with bilateral posterior contacts was fabricated to protect her oral mucosa. On reevaluation, excessive movement of the jaw/tongue was significantly reduced with the presence of the appliance in her mouth. Face/neck muscle tenderness was also greatly reduced. The use of oral appliance therapy in TD patients plays an important role in protecting the teeth/oral mucosa. The subsequent inhibition of excessive motor activity is proposed and should be further investigated.
Article
The atypical antipsychotics are a new class of agents with great promise for use in the elderly because of their reduced propensity to cause acute extrapyramidal adverse effects. Treatment of older patients with these agents, however, needs to take into consideration age-related changes in pharmacokinetics and the risks of drug-drug interactions. Additionally, current evidence of their efficacy in late-life psychoses is derived largely from case series and from the extrapolation of results obtained in studies of younger patients with schizophrenia. Controlled clinical studies of atypical antipsychotics in elderly patients are urgently needed.
Chapter
Treatment with antipsychotics is often complicated by side effects, whether slight and harmless or severe and potentially lethal. Severe side effects are a major cause of poor compliance, which in turn has implications for relapse, hospitalization, and morbidity. They cause suffering for patients and relatives, limit possibilities for rehabilitation and leisure activities, and deter social integration. At times, they counteract therapeutic efficacy and may even lead to suicide. Finally, some side effects may become irreversible, thereby entailing a risk of persistent damage to the central nervous system.
Article
Antipsychotic drugs can be of great benefit in a range of psychiatric disorders, including schizophrenia and bipolar disorder, but all are associated with a wide range of potential adverse effects. These can impair quality of life, cause stigma, lead to poor adherence with medication, cause physical morbidity and, in extreme cases, be fatal. A comprehensive overview of tolerability requires a review of all available data, including randomised controlled trials (RCTs), observational studies and postmarketing surveillance studies. Assessing the relative tolerability of atypical antipsychotics is hampered by the paucity of RCTs that compare these drugs head-to-head, and limited and inconsistent reporting of adverse effect data that makes cross-study comparisons difficult. Despite methodological problems in assessment and interpretation of tolerability data, important differences exist between the atypical antipsychotics in the relative risk of acute extrapyramidal symptoms (highest risk: higher doses of risperidone), hyperglycaemia and dyslipidaemia (highest risk: clozapine and olanzapine), hyperprolactinaemia (highest risk: amisulpride and risperidone), prolongation of heart rate-corrected QT interval (QTc) [highest risk: ziprasidone and sertindole] and weight gain (highest risk: clozapine and olanzapine). Sedation, antimuscarinic symptoms, postural hypotension, agranulocytosis and seizures are more common with clozapine than with other atypical antipsychotics. The variation in their tolerability suggests that it is misleading to regard the atypical antipsychotics as a uniform drug class, and also means that the term ‘atypical antipsychotic’ has only limited usefulness. Differences between the atypical agents in terms of efficacy and pharmacodynamic profiles also support this view. As tolerability differs between specific conventional and atypical drugs, we conclude that broad statements comparing the relative risk of specific adverse effects between ‘atypical’ and ‘conventional’ antipsychotics are largely meaningless; rather, comparisons should be made between specific atypical and specific conventional drugs. Adverse effects are usually dose dependent and can be influenced by patient characteristics, including age and gender. These confounding factors should be considered in clinical practice and in the interpretation of research data. Selection of an antipsychotic should be on an individual patient basis. Patients should be involved in prescribing decisions and this should involve discussion about adverse effects.
Thesis
Schizophrenia, the most common form of psychosis, is a chronic disorder that usually develops in early adulthood and often leads to life long disability. Over the last decade, the transfer of patients with chronic schizophrenia from long stay hospitals to the community has had an impact on the extent of involvement of the general practitioners in the care of patients with schizophrenia. Little, however, is known about the role of the general practitioner in the management of patients with schizophrenia. The study described in this thesis tests the hypothesis that the diagnosis of psychosis recorded on a general practice computer system is accurate and that patients with schizophrenia present a high workload in general practice. The study also determines the views of patients and general practitioners about the services currently offered in a group of London general practices. Sixteen general practices in London consisting of 28 general practitioners and 72,000 registered patients were recruited to the study. After validation of the diagnoses of psychoses as entered on the general practice computers, a sample of patients and all the general practitioners involved in their care were interviewed to assess their views on the service provided. Lastly, a comparative assessment was made of the care offered to all patients with schizophrenia and age and sex matched controls. The diagnoses of schizophrenia and other related psychosis as entered on the practice computers was accurate. The overall prevalence of schizophrenia in these practice was 3.0 per 1000, with a higher prevalence in the inner city practices (3.75 per 1000) compared to suburban practices (2 per 1000) . The patients' views on the services offered to them were not always in accordance with those of the general practitioners. Patients with schizophrenia, attended the surgery as frequently as other patients with chronic physical diseases but significantly more often than patients randomly selected from the general practice age sex register. The care offered to patients with schizophrenia, was less structured than that provided to other patients with chronic physical diseases. General practitioners are increasingly involved in the care of patients with schizophrenia. There is a need, however, to consider a more structured approach to their management. General practice computers can be effectively used to identify patients. Before developing a practice based care plan, it is essential to identify the need of the patients and the professionals involved in their care. This study provides a detailed account of the management currently offered in general practice and will assist general practitioners and mental health professionals in developing a more structured approach to the care of patients with schizophrenia in general practice.
Article
Tardive syndrome (TS) is an iatrogenic, often persistent movement disorder caused by drugs that block dopamine receptors. It has a broad phenotype including movement (orobuccolingual stereotypy, dystonia, tics, and others) and nonmotor features (akathisia and pain). TS has garnered increased attention of late because of the Food and Drug Administration approval of the first therapeutic agents developed specifically for this purpose. This paper will begin with a discussion on pathogenesis, clinical features, and epidemiology. However, the main focus will be treatment options currently available for TS including a suggested algorithm based on current evidence. Recently, there have been significant advances in TS therapy, particularly with the development of 2 new vesicular monoamine transporter type 2 inhibitors for TS and with new data on the efficacy of deep brain stimulation. The discussion will start with switching antipsychotics and the use of clozapine monotherapy which, despite the lack of higher-level evidence, should be considered for the treatment of psychosis and TS. Anti-dyskinetic drugs are separated into 3 tiers: 1) vesicular monoamine transporter type 2 inhibitors, which have level A evidence, are approved for use in TS and are recommended first-choice agents; 2) drugs with lower level of evidence for efficacy including clonazepam, Ginkgo biloba, and amantadine; and 3) drugs that have the potential to be beneficial, but currently have insufficient evidence including levetiracetam, piracetam, vitamin B6, melatonin, baclofen, propranolol, zolpidem, and zonisamide. Finally, the roles of botulinum toxin and surgical therapy will be examined. Current therapies, though improved, are symptomatic. Next steps should focus on the prevention and reversal of the pathogenic process.
Article
Tardive dyskinesia is a serious, disabling and potentially permanent, neurological hyperkinetic movement disorder that occurs after months or years of taking psychotropic drugs. The pathophysiology of tardive dyskinesia is complex, multifactorial and still not fully understood. A number of drugs were tried for the management of this motor disturbance, yet until now no effective and standard treatment has been found. It is very disappointing to realize that the introduction of antipsychotics from the second generation did not significantly decrease the prevalence and incidence of tardive dyskinesia. Therefore, the management of this motor disturbance remains an actual topic as well as a challenge for clinicians. This review summarizes recent relevant publications concerning the treatment of tardive dyskinesia.
Article
Olanzapine is an atypical antipsychotic that has a pharmacological profile similar that of clozapine. It is biotransformed by hepatic enzymes and can be dosed on a once-daily basis. In large, double-blind, placebo- controlled trials, olanzapine was shown to be efficacious in the treatment of schizophrenia relative to placebo. Many trials showed superior efficacy to haloperidol, especially against negative symptoms. Olanzapine is FDA-approved for the treatment of psychotic disorders, though data suggest possible use in depression, bipolar disorder, psychogenic polydipsia, and developmental disabilities. Olanzapine appears to be well-tolerated. Commonly reported adverse effects include orthostatic hypotension, sedation, hepatic transaminase elevations, weight gain, headache, agitation, dizziness, and constipation. The incidence of extrapyramidal symptoms and tardive dyskinesia is low. Few drug interactions have been reported. The recommended starting dose is 10 mg once daily one trial indicated that the higher cost of this agent might be offset by a reduction in overall hospitalization costs.
Chapter
Zwei Jahre, nachdem Delay und Deniker (1952) anlässlich einer Konferenz in Luxembourg erstmals ihre Erfahrungen mit dem später Chlorpromazin genannten RP 4560 bei der Behandlung deliranter und psychotischer Patienten referiert hatten, berichtete der Schweizer Neurologe Hans Steck über ein reversibles, dosisabhängiges extrapyramidales Syndrom mit Parkinsonismus und Akathisie, das er unter der Behandlung mit Chlorpromazin und Reserpin an 111 von 299 (37%) meist chronisch schizophrenen Patienten beobachtet hatte (Steck 1954). In Anlehnung an eine vergleichbare Symptomatik im Verlauf der Encephalitis lethargica (sein Spezialgebiet) benannte Steck die beobachtete Symptomatik als »extrapyramidales-diencephalesº Syndrom. Aufgrund früherer Beobachtungen an chronisch Schizophrenen, bei denen die Entwicklung eines Parkinson-Syndroms im Rahmen einer zusätzlichen Erkrankung an Encephalitis lethargica zu einer Besserung der schizophrenen Symptomatik geführt hatte, entwickelte Steck die nach ihm benannte Hypothese, dass Chlorpromazin ähnlich einer Encephalitis den natürlichen Verlauf der psychotischen Krankheit von einem erregten Initialstadium zu einem akinetischen, durch Aktivitätsverlust charakterisierten Stadium bis hin zur Möglichkeit einer Spontanheilung beschleunigen würde.
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Schizophrenia and Psychoses in Later Life - edited by Carl I. Cohen March 2019
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Spätdyskinesien sind eine der schwerwiegendsten Nebenwirkungen der Langzeittherapie mit Antipsychotika bzw. Neuroleptika. Im englischen Sprachraum werden sie tardive Dyskinesien, abgekürzt TD, genannt. Sie sind charakterisiert durch unwillkürliche Bewegungsanomalien der Zunge, des Kiefers, des Rumpfes oder der Extremitäten, welche sich im Zusammenhang mit der Einnahme von Neuroleptika entwickeln. Deshalb nennt sie das DSM-IV neuroleptikainduzierte tardive Dyskinesien (1996).
Chapter
Viele neurologische Krankheitsbilder sind Erkrankungen, deren Ursache in einer substanziellen oder funktionellen Störung des Zentralnervensystems zu suchen ist, und die häufig eine psychiatrische Komorbidität aufweisen, deren Existenz wiederum nicht unbedingt als unabhängig zur neurologischen Erkrankung, sondern oft mals durch die Hirnschädigung als mitbedingt zu betrachten ist.
Article
Full-text available
The purpose of the present work was to study the clinical features and risk factors of tardive dyskinesia among the schizophrenia patients who durably receive the antipsychotic therapy. 180 of the 18 to 65 age bracket schizophrenia patients, who were treated in a residential psychiatric treatment facility, were examined with the use of the Positive and Negative Syndrome Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), and the basic chart of formalized sociodemographic and clinico-dynamic features developed at the Tomsk Mental Health Research Institute. The acquired data were processed by the Mann–Whitney U-Test and χ2. The average age of the tardive dyskinesia patients turned out to be conclusively older than that of the patients without this derangement. People who have tardive dyskinesia statistically often happen to be single in comparison with other variants of marital status. It was found out that women happen to have tardive dyskinesia more often, which allows us to see the female gender as a risk factor. The tardive dyskinesia patients had certain negative symptoms. The patients were arranged into groups according to the prepotency of symptom-complexes over the subgroups: with orofacial, thoracolumbar and combined tardive dyskinesia. The average age of the orofacial dyskinesia patients turned out to be conclusively older than that of the patients without tardive dyskinesia. The negative symptoms level in the subgroup was conclusively higher than among those without tardive dyskinesia. The average age of the thoracolumbar dyskinesia patients was conclusively older than that of the patients without tardive dyskinesia. The average age of the combined dyskinesia patients was conclusively older than the patients without the tardive dyskinesia. The patients having schizophrenia for longer than 10 years prevailed in the combined dyskinesia group. Such characteristics as education level and social status, age of when the medical problem started, dominance of the positive symptoms, duration of antipsychotic agents administration, somatic condition, use of psychoactive substances, suicidal and hetero-aggressive behaviors make no contribution to the risk of tardive dyskinesia development in the presence of schizophrenia, and they are not protective factors either.
Article
There has been an ongoing debate regarding the forced use of antipsychotic medications and both the psychiatric and legal professions have reacted strongly to the growing debate. Within the penological context, cases such as Washington v. Harper, Riggins v. Nevada, and Sell v. United States established the framework for determining when antipsychotic medication may be forcibly administered. Medication decisions under the Sell and Riggins cases are to be approved at judicial hearings; whereas, administrative hearings are sufficient for Harper cases. Forensic psychiatrists are also given responsibility in making the legal decision of whether or not to forcibly treat a patient with psychotropic medication against his will. In making this critical decision, a significant factor that is often minimized is the cultural background of the patient. The purpose of this paper is to present cultural factors to be considered in forced medication. Focusing on the culture defense argument, a review of how the legal system has dealt with cultural implications of a case will be presented. This paper will then discuss cultural issues embedded in the assessment, diagnosis, and treatment of psychiatric patients by forensic psychiatrists who are called upon to make the decision of whether or not to force medicate a patient against his will. Lastly, recommendations and a framework for providing a culturally sensitive assessment during the decision to forcibly medicate a patient with psychotropic medication will be offered.
Article
This cross-sectional study examines the differences in cortical volume and gray-to-white matter contrast (GWC) in first episode schizophrenia patients (SCZ) compared to healthy control participants (HC) and in SCZ patients as a function of exposure to second generation antipsychotic medication. We hypothesize 1) SCZ exhibit regionally lower cortical volumes relative to HCs, 2) cortical volume will be greater with longer exposure to second generation antipsychotics prior to the MRI scan, and 3) lower GWC with longer exposure to second generation antipsychotics prior to the MRI scan, suggesting more blurring from greater intracortical myelin. To accomplish this, MRI scans from 71 male SCZ patients treated with second generation oral risperidone and 42 male HCs were examined. 3D T1-weighted MPRAGE images collected at 1.5T were used to estimate cortical volume and GWC by sampling signal intensity at 30% within the cortical ribbon. Average cortical volume and GWC were calculated and compared between SCZ and HC. Cortical volume and GWC in SCZ patients were correlated with duration of medication exposure for the time period prior to the scan. First-episode SCZ patients had significantly lower cortical volume compared to HCs in bilateral temporal, superior and rostral frontal, postcentral gyral, and parahippocampal regions. In SCZ patients, greater cortical volume was associated with (log-transformed) duration of second-generation antipsychotic medication exposure in bilateral precuneus, right lingual, and right superior parietal regions. Lower GWC was correlated with longer duration of medication exposure bilaterally in the superior frontal lobes. In summary, second generation antipsychotics may increase cortical volume and decrease GWC in first episode SCZ patients.
Article
Hyperkinetic movement disorders comprise a variety of conditions characterized by involuntary movements, which include but are not limited to tardive dyskinesia, chorea associated with Huntington's Disease, and tic disorders. The class of medications that have been used to treat these conditions includes Vesicular Monoamine Transporter-2 (VMAT2) inhibitors. In 2008, the FDA approved tetrabenazine as a treatment for chorea associated with Huntington's Disease. Optimization of the pharmacology of tetrabenazine has since led to the approval of two new VMAT2 inhibitors, deutetrabenazine and valbenazine. The objective of this review is to provide background on the role of VMAT in monoamine neurotransmission, the mechanism of VMAT2 inhibition on the treatment of hyperkinetic disorders (specifically tardive dyskinesia and chorea associated with Huntington's Disease), the pharmacology and pharmacokinetics of the commercially available VMAT2 inhibitors, and a summary of the clinical data to support application of these medications.
Article
Tardive dyskinesia (TD) is an iatrogenic condition that encompasses a wide phenomenological spectrum of movement disorders caused by exposure to dopamine receptor blocking agents (DRBAs). TD may cause troublesome or disabling symptoms that impair quality of life. Due to frequent, often inappropriate, use of DRBAs, TD prevalence rates among patients exposed to DRBAs continue to be high. The judicious use of DRBAs is key to the prevention of TD, reduction of disease burden, and achieving lasting remission. Dopamine-depleting vesicular monoamine transporter type 2 inhibitors are considered the treatment of choice of TD.
Article
The approvals of the first two medications, valbenazine and deutetrabenazine, to treat tardive dyskinesia have ushered in a new era in neuropsychiatric care. Tardive syndromes are defined as delayed onset, persistent movement disorders or sensory phenomena that occur in association with exposure to dopamine receptor blocking agents (DRBAs). Their underlying pathophysiology remains to be fully elucidated, but clinicians can conceptualize tardive syndromes as persistent dopamine supersensitivity states. Tardive syndromes can potentially cause distress, disfigurement, embarrassment, and dysfunction, and are often permanent. Therefore, practitioners who prescribe DRBAs should be aware of this potential, carefully assess the risk/benefit ratio when considering the use of these medications, and be sure that patients are appropriately informed. Patients on DRBAs should be monitored for the development of tardive syndromes, including through the use of regularly scheduled Abnormal Involuntary Movement Scale (AIMS) (or similar) examinations. Clinicians prescribing DRBAs should be familiar with the diagnosis and management of tardive syndromes, and be able to institute treatment or refer patients when treatment is appropriate. Future research may focus on the potential benefit of earlier introduction of VMAT2 inhibitors to delay onset or progression of tardive syndromes. More effective treatments are still needed, as are effective, well-tolerated antipsychotics that do not cause tardive syndromes.
Article
Since the original description of side effects of neuroleptics, different terminologies and definitions for tardive dyskinesia (TD) and tardive syndrome (TS) have been used by different authors, and often these two terms have been used interchangeably. This paper proposes a nosology designed to define and clarify various terms and phenomenologies within the TS spectrum. We propose to use the term tardive dyskinesia to refer to the original description of repetitive and complex oral-buccal-lingual (OBL) movements, as well as to the analogous repetitive movements that can appear in the limbs, trunk, or pelvis. The repetitive, relatively rhythmic nature of the movements is the common denominator of this phenomenologic category. The term tardive syndrome refers to the spectrum of all persistent hyperkinetic, hypokinetic and sensory phenomenologies resulting from chronic dopamine receptor blocking agents (DRBA) exposure. Thus, TS is an umbrella term. When dystonia is the main feature of TS it is considered to be tardive dystonia (TDyst). Retrocollis appears to be the predominant form of cervical dystonia in this condition. Cranial dystonias, particularly oromandibular dystonia, are also common forms of TDyst. Tardive akathisia refers to the inability to remain still with an urge to move, giving the appearance of restlessness. It is a sensory phenomenon and a common and disabling form of TS. Unlike acute akathisia, tardive akathisia tends to occur late and persists after the drug is withdrawn. In tardive tourettism, the patient exhibits the features of Tourette syndrome with complex motor and phonic tics associated with premonitory urge and relief of tension after performing the tic behavior. Tardive tremor differs from the resting tremor seen in drug-induced parkinsonism in that it is mainly a postural and kinetic greater than resting tremor. Tardive pain has been reported in association with chronic use of DRBA's. The pain involved the mouth, tongue and the genital region. The patients tended to obsess over the pain and usually had some other form of motor tardive syndrome, either tardive dyskinesia, tardive akathisia or tardive dystonia. The term tardive parkinsonism has been proposed for those drug induced parkinsonism patients who have persistent symptoms following discontinuation of the DRBA. However, there is a strong possibility that the DRBA may have simply unmasked subclinical parkinsonism or that there is coincident Parkinson disease developing during the period the patient is taking the DRBA.
Article
Tardive dyskinesia (TD) encompasses the spectrum of iatrogenic hyperkinetic movement disorders following exposure to dopamine receptor-blocking agents (DRBAs). Despite the advent of atypical or second- and third-generation antipsychotics with a presumably lower risk of complications, TD remains a persistent and challenging problem. Prevention is the first step in mitigating the risk of TD, but early recognition, gradual withdrawal of offending medications, and appropriate treatment are also critical. As TD is often a persistent and troublesome disorder, specific antidyskinetic therapies are often needed for symptomatic relief. The vesicular monoamine transporter 2 (VMAT2) inhibitors, which include tetrabenazine, deutetrabenazine, and valbenazine, are considered the treatment of choice for most patients with TD. Deutetrabenazine—a deuterated version of tetrabenazine—and valbenazine, the purified parent product of one of the main tetrabenazine metabolites, are novel VMAT2 inhibitors and the only drugs to receive approval from the US FDA for the treatment of TD. VMAT2 inhibitors deplete presynaptic dopamine and reduce involuntary movements in many hyperkinetic movement disorders, particularly TD, Huntington disease, and Tourette syndrome. The active metabolites of the VMAT2 inhibitors have high affinity for VMAT2 and minimal off-target binding. Compared with tetrabenazine, deutetrabenazine and valbenazine have pharmacokinetic advantages that translate into less frequent dosing and better tolerability. However, no head-to-head studies have compared the various VMAT2 inhibitors. One of the major advantages of VMAT2 inhibitors over DRBAs, which are still being used by some clinicians in the treatment of some hyperkinetic disorders, including TD, is that they are not associated with the development of TD. We also briefly discuss other treatment options for TD, including amantadine, clonazepam, Gingko biloba, zolpidem, botulinum toxin, and deep brain stimulation. Treatment of TD and other drug-induced movement disorders must be individualized and based on the severity, phenomenology, potential side effects, and other factors discussed in this review.
Article
These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment. They were asked to review key areas and consider the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement.
Article
Tardive dyskinesia is a common iatrogenic neurological and neurobehavioural syndrome associated with the use of antidopaminergic medication, especially antipsychotics. Prior to the introduction of the newer antipsychotics in the 1990s, it was one of the major areas of psychiatric research but interest waned as the new drugs were reputed to have a reduced liability to extrapyramidal adverse effects in general, a claim now discredited by numerous pragmatic research studies. Early small-scale short-term prevalence studies were presented as evidence to support the assumption that patients on the newer drugs did indeed have a lower prevalence of tardive dyskinesia but recent large-scale review of studies with patients exposed for longer suggest that things have not changed. This article presents a clinical overview of a complex and varied syndrome in terms of its phenomenology, epidemiology and risk factors; a companion article will consider treatment. This overview aims to highlight tardive dyskinesia once again, especially to practitioners who have trained in an environment where this was considered mainly in historical terms. LEARNING OBJECTIVES • Understand the complex phenomenology comprising the syndrome of tardive dyskinesia • Appreciate recent data on prevalence and incidence with the newer antipsychotics • Be aware of risk factors when recommending antipsychotic (and other antidopaminergic) drugs DECLARATION OF INTEREST None.
Chapter
In diesem Kapitel erfolgt die Darstellung der allgemeinen und spezifischen Pharmakotherapie, sowie weiterer somatischer Behandlungsverfahren für die Therapie von Menschen mit einer Schizophrenie. Weiterhin werden die Nebenwirkungen einer antipsychotischen Behandlung sowie deren Diagnostik und Therapie dargestellt.
Article
Movement disorders attributable to prescribed medications and drugs of abuse are commonly encountered in the clinic. This chapter will review the wide variety of movement disorders due to dopamine-receptor blocking agents (DBAs), other medications, and the drugs of abuse. Movement disorders due to DBAs Antipsychotic agents, also termed neuroleptics or dopamine-receptor blocking agents (DBAs), are extensively utilized in the management of psychiatric disorders such as schizophrenia and bipolar disorders, and DBAs are employed in the treatment of neurological diseases such as Tourette’s syndrome, Huntington’s disease, psychosis in Parkinson’s disease, and dementias such as dementia with Lewy bodies. In addition, metoclopramide (MCP) is widely used to treat gastrointestinal motility disorders. The introduction of chlorpromazine in the early 1950s was nothing short of a miracle in the treatment of psychosis, but it was soon realized that there were significant neurological side effects associated with this class of drugs. Extrapyramidal side effects (EPS) was an umbrella term used to describe these side effects. Initially, it was thought that the induction of EPS was integral to the clinical antipsychotic efficacy of chlorpromazine and a dopamine depleter reserpine. More recently with the advent of clozapine, this tight linkage between EPS and antipsychotic efficacy has been shown to be fallacious. The evidence implicates the degree of D2 receptor antagonism and the speed of dissociation in the development of these EPS (DBAs with less D2 affinity and more rapid dissociation are less likely to produce EPS). In addition, the blockage of other neurotransmitter receptors such as 5-hydroxytryptamine (5-HT2) receptors may be important, allowing the development of drugs that are less likely to cause movement disorders.
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