Matson Evaluation of Drug Side-effects (MEDS) Profiles in Adults with Intellectual Disability,Tardive Dyskinesia,and Akathisia

Drug side effect profiles of 161 intellectually disabled inpatient adults were assessed with the Matson Evaluation of Drug Side Effects (MEDS). Based on diagnoses made by a board certified psychiatrist and a neurologist specializing in movement disorders, participants were divided into three groups: controls (no movement disorder), tardive dyskinesia (TD), and a group with tardive dyskinesia/akathisia (TD Akathisia). Significant differences in side effects were noted between all three groups with the most severe side effects occurring in the TD Akathisia group. Group differences between the TD and TD Akathisia groups were most pronounced on CNS-Parkinsonism/Dyskinesia, CNS-Behavioral Akathisia, and CNS-Dystonia subscales, with the latter side effect group experiencing the greatest side effects. Implications of these data are discussed and future research is suggested.     

Side effects of antipsychotic drugs. Avoiding and minimizing their impact in elderly patients

Antipsychotic drugs are very useful in treatment of psychosis and severe agitation in the elderly. Their use for other behavioral problems is contraindicated. Antipsychotics have many potential side effects (e.g., sedation, cardiovascular effects, anticholinergic effects, incontinence, reduced appetite, such motor disturbances as drug-induced parkinsonism, akathisia, dystonia, TD). Prevention, by using the minimum dose and duration of treatment possible, is the key to managing motor side effects. If prevention fails, drug-induced parkinsonism and dystonia may improve with use of anticholinergics, and akathisia may improve with use of benzodiazepines or low-dose propranolol. There is no proven treatment for TD, which is most likely to be observed during dose reduction or after discontinuation of antipsychotic drugs. Compared with older agents, newer antipsychotic drugs are less likely to cause parkinsonism, akathisia, and dystonia and may cause TD less often. More research is needed to clarify use of the new drugs in the elderly.     

Use of antipsychotic drugs in depression. Problems and opportunities

Antipsychotic drugs have an important place in pharmacologic treatment of depression. Major depression with psychotic features responds poorly to treatment if an antipsychotic is not used in addition to an antidepressant; however, an antipsychotic confers no additional benefit in nonpsychotic depression. Antipsychotic drugs do have significant short- and long-term side effects, including pseudoparkinsonism, dystonia, akathisia, and tardive dyskinesia. The possibility of a good therapeutic response with minimal side effects can be increased if psychotic depression is diagnosed accurately and the antipsychotic is prescribed according to established clinical guidelines.     

Detection,Prevention, and Management of Extrapyramidal Symptoms

Extrapyramidal symptoms (EPSs), such as akathisia, dystonia, psuedoparkinsonism, and dyskinesia, are drug-induced side effects that can be problematic for persons who receive antipsychotic medications (APMs) or other dopamine-blocking agents. The clinical manifestations include a number of atypical involuntary muscle contractions that influence gait, movement, and posture. The symptoms can develop acutely, be delayed, or overlap making diagnosing a challenge. Preventive interventions include selective prescribing of APMs, close monitoring of uncharacteristic movements through the use of screening instruments, prompt management of symptoms, and thorough client education. Nurse practitioners who do not practice in psychiatric mental health nursing on a regular basis or who infrequently prescribe psychotropic medications must be cautious with these potential life-threatening symptoms.     

Clozapine: a novel antipsychotic.

Clozapine is the first truly new antipsychotic drug introduced in the last 40 years. Compared to traditional neuroleptic agents, clozapine appears to have a stronger effect on most schizophrenic symptoms. Thus, it seems to be more effective than other agents in severely ill, treatment-resistant patients. Clozapine rarely causes extrapyramidal symptoms such as pseudoparkinsonism or akathisia. To date, no confirmed cases of tardive dyskinesia have been attributed to the drug. Despite these advantages, the usefulness of clozapine is limited by its potentially life-threatening side effects, which include agranulocytosis and respiratory depression.     

Atypical antipsychotics: experience and use in the elderly

The use of antipsychotics is common in the elderly Typical antipsychotics are not without risk, especially in tardive dyskinesia, which, when balanced against relatively low efficacy, make their use debatable. Atypical antipsychotics have much less in the way of side-effects and are much less likely to induce tardive dyskinesia. However, there is much less in the published literature about the efficacy of these drugs in the elderly and how best to use them in primary psychosis, Parkinson's disease and the behavioural and psychological symptoms of dementia. This review attempts to summarise the current literature and make some tentative recommendations for each of the commonest atypicals, based on the current evidence.     

Hospitalization risk associated with typical and atypical antipsychotic use in community-dwelling elderly patients

Background: Due to age-related changes in drug disposition and response, elderly patients are more susceptible to the adverse effects of antipsychotic medications than younger adults. However, few studies have examined the impact of typical and atypical antipsychotic use on all-cause hospitalization in the elderly population.Objective: This study compared the short-term effects of incident use of typical and atypical antipsychotic agents on the risk for hospitalization in a community-dwelling elderly population.Methods: This retrospective data analysis involved a longitudinal cohort of typical and atypical antipsychotic users and was based on data from the 1996–2004 Medical Expenditure Panel Survey. Typical antipsychotic agents included chlorpromazine, fluphenazine, haloperidol, levomepromazine, loxapine, mesoridazine, molindone, perphenazine, promazine, thioridazine, thiothixene, and trifluoperazine. Atypical antipsychotic agents included aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Incident cases of antipsychotic use in community-dwelling elderly (aged ≥60 years) persons were selected for the assessment of risk for all-cause hospitalization within 60 days of exposure to antipsychotics. Bivariate analyses were used to compare baseline characteristics; multivariate logistic regression was used to compare hospitalization risk among users of typicals and atypicals after controlling for age, sex, race, income, insurance coverage, perceived general health, perceived mental health, and other concurrent psychotropic use.Results: The analytical sample consisted of 124 community-dwelling elderly patients (atypicals, 75 patients; typicals, 49). A majority of the elderly study sample were women (63%), white (79%), and of middle/high income (57%). The mean (SD) age of the study sample was 74.37 (8.65) years. There were no significant differences in baseline characteristics between typical and atypical users, with the exception of perceived mental health status. After controlling for other factors, the risk for hospitalization was nearly 4-fold higher with typical antipsychotic use than atypical use (odds ratio, 3.81; 95% CI, 1.12–12.99).Conclusion: In this population of community-dwelling elderly, use of typical agents was associated with an increased risk for hospitalization compared with atypical agents.     

Pharmacogenetics of antipsychotic treatment response and side effects

Antipsychotic drugs are particularly interesting in pharmacogenetic studies as they are associated with a large interindividual variability in terms of response and side effects and, therefore, frequently need to be discontinued, requiring switches to other antipsychotics. Any information that allows the prediction of outcome to a given antipsychotic in a particular patient will, therefore, be of great help for the clinician to minimize time and find the right drug for the right patient, thus optimizing response and minimizing side effects. This will also have a substantial impact on compliance and doctor-patient relationships. Moreover, antipsychotic drug treatments are often required for life-long treatment and are also frequently prescribed to the more 'vulnerable' populations: children, adolescents and the elderly. This article focuses on some important studies performed with candidate gene variants associated with antipsychotic response. In addition, important findings in pharmacogenetic studies of antipsychotic-induced side effects will be briefly summarized, such as antipsychotic treatment induced tardive dyskinesia and weight gain.     

Development of a screening tool to assess risk of tardive dyskinesia

This article gives an overview of antipsychotic medication and of tardive dyskinesia (TD). It examines the research available on TD as it relates to people with a learning disability (PWLD). The evidence identifies that specific groups of people are at an increased risk of developing TD. It also shows that 45-50% of PWLD who are treated with antipsychotic medication will be affected by TD. The evidence is used in the formulation of an assessment tool designed for use by the community learning disability nurse to identify an individual's risk of developing TD before commencing medication. Litigation in the USA has led to a $6.7 m award for sound, clinically effective practice and evidence-based interventions requires that practitioners are accountable for their practice, but are also seen to transform existing services in a way which improves the delivery of quality interventions and care.     

Discrete state analysis for interpretation of data from clinical trials

OBJECTIVE: The objective of this study was to demonstrate a multivariate health state approach to analyzing complex disease data that allows projection of long-term outcomes using clustering, Markov modeling, and preference weights. SUBJECTS: We studied patients hospitalized 30 to 364 days with refractory schizophrenia at 15 Veterans Affairs medical centers. STUDY DESIGN: We conducted a randomized clinical trial comparing clozapine, an atypical antipsychotic, and haloperidol, a conventional antipsychotic. METHODS: Health status instruments measuring disease-related symptoms and drug side effects were administered in face-to-face interviews at baseline, 6 weeks, and quarterly follow-up intervals for 1 year. Cost data were derived from Veterans Affairs records supplemented by interviews. K-means clustering was used to identify a small number of health states for each instrument. Markov modeling was used to estimate long-term outcomes. RESULTS: Multivariate models with 7 and 6 states, respectively, were required to describe patterns of psychiatric symptoms and side effects (movement disorders). Clozapine increased the proportion of clients in states characterized by mild psychiatric symptoms and decreased the proportion with severe positive symptoms but showed no long-term benefit for negative symptoms. Clozapine dramatically increased the proportion of patients with no movement side effects and decreased incidences of mild akathisia. Effects on extrapyramidal symptoms and tardive dyskinesia were far less pronounced and slower to develop. Markov modeling confirms the consistency of these findings. CONCLUSIONS: Analyzing complex disease data using multivariate health state models allows a richer understanding of trial effects and projection of long-term outcomes. Although clozapine generates substantially fewer side effects than haloperidol, its impact on psychiatric aspects of schizophrenia is less robust and primarily involves positive symptoms.     

Pharmacologic treatment of schizophrenia.

The literature on the pharmacologic treatment of schizophrenia and schizoaffective disorders is reviewed (116 references). All clinically active antipsychotic drugs share the ability to block postsynaptic dopamine receptors in the central nervous system. Their potencies vary, chlorpromazine and thioridazine being the least potent and fluphenazine and haloperidol the most potent. The adverse effects of the neuroleptics include acute dystonia, parkinsonian symptoms (extrapyramidal symptoms), akathisia, tardive dyskinesia, and tardive dystonia. When used at equipotent doses, all classic neuroleptics now available are equally effective in the treatment of schizophrenia. Choice of drug is based on adverse effects and patient response. The neuroleptics are effective in most acute exacerbations of schizophrenia and for the prevention or mitigation of relapse. Their effects are more pronounced on the positive symptoms of schizophrenia, such as hallucinations, delusions, disordered thinking, and paranoia, than on the negative symptoms, such as deficits in social interaction, emotional expression, and motivation. Strategies for acute and maintenance treatment and for the management of treatment-resistant patients are reviewed. The pharmacology and clinical use of the newer atypical neuroleptics, particularly clozapine, and their adverse effects are discussed.     

Antipsychotic drugs

Antipsychotic drugs have been widely used in the treatment of organic, including symptomatic, mental disorders. The guidelines for the treatment of delirium suggest using atypical antipsychotic drugs for the patients with excitement. Atypical antipsychotic drugs show higher affinity for 5-HT2A receptor than D2 receptor. The extrapyramidal side effects of atypical antipsychotic drugs are less than of conventional antipsychotic drugs, so they can be used more safely in the medication for elderly patients. However, we must pay attention to the risk of hyperglycemia, diabetic ketoacidosis and sudden cardiac death. Because of off-label use, well informed consents about effectiveness and safety are necessary.     

迟发性运动障碍的临床诊治进展

迟发性运动障碍(tardive dyskinesia, TD)是与长期服用多巴胺受体阻滞剂相关的一种异常不自主运动,可累及面颈部,引起伸舌、咀嚼、噘嘴、歪颌或转颈,也可累及四肢和躯干,表现为舞蹈样动作。临床上最常见的病因为抗精神病药物(antipsychotic drug, APD)的使用。与TD相关的危险因素包括APD的种类、用药剂量和时间、年龄和性别,遗传因素也发挥一定作用。目前研究较多的TD相关基因为CYP2D6、DRD2、DRD3、HTR2A、HTR2C、VMAT2、MnSOD、HSPG2。TD的发病机制尚不明确,主要有多巴胺受体超敏学说、氧化应激学说和突触可塑性失调学说。临床上治疗TD较为困难,预防至关重要。本文就TD的临床诊治进展进行综述,以进一步加深医务人员对该疾病的认识。     

Reliability and validity of three rating scales for assessing tardive dyskinesia in individuals with developmental disabilities

The incorporation of a standardized assessment and monitoring procedure for TD into the treatment plans for all individuals prescribed antipsychotic medications has become the standard of care. There are several well-known and established rating scales designed specifically for this purpose. The AIMS and the DISCUS are two of the most commonly used instruments to detect and monitor abnormal movements associated with TD in individuals with developmental disabilities. The CLAMPS is a newly developed rating scale also designed for use in individuals with developmental disabilities to monitor for and assess abnormal movements, including those associated with TD and other disorders. In this study, we investigated the concurrent validity and interrater reliability of these three scales in a sample of seven adults with mental retardation and TD. The results indicated that, overall, the dyskinesia subscales of the CLAMPS showed the greatest level of agreement with the DISCUS subscales. Lower levels of agreement were observed between the CLAMPS and AIMS dyskinesia subscales. The degree of interrater reliability observed for the AIMS and DISCUS subscale scores was consistent with that found in previous research and, with the exception of three subscales, the CLAMPS demonstrated an interrater reliability of a magnitude comparable to the other two. There are some advantages of the CLAMPS and further research on this rating scale is warranted.     

Schizophrenia,tardive dyskinesia,and the Abnormal Involuntary Movement Scale (AIMS)

The incidence of tardive dyskinesia as a side effect of antipsychotic medications is well documented in the literature on the treatment for schizophrenia. Although the new generation of atypical neuroleptics helps diminish the incidence of such side effects, a complete elimination has yet to be fully realized. Nurses continually observe and assess patients. As such, nurses in all settings can effectively contribute to both preventative and palliative care of the patient who is about to receive or is currently receiving antipsychotic medications. Familiarity with the Abnormal Involuntary Movement Scale (AIMS) and expertise in the application of AIMS in patient assessment assist in these important prevention efforts. (J Am Psychiatr Nurses Assoc [2002]. 8, 51-6.)     

Nicotine reduces antipsychotic-induced orofacial dyskinesia in rats

Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs by ～20% after 5 weeks, with a significant ～60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and α6β2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced α4β2* nAChRs in both vehicle and haloperidol-treated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use.     

A Case of Tardive Dyskinesia in the Last Weeks of Life

Tardive dyskinesia (TD) is a chronic and often irreversible movement disorder that usually evolves after years of neuroleptic use but can sometimes develop over a much shorter time frame. Paradoxically, a higher dose of the neuroleptic agent that causes TD can often temporarily suppress the movement disorder. This is generally an inadvisable approach, though, as its effectiveness is probably limited to only a matter of weeks and as it will worsen the problem in the long run. We describe a patient with widely metastatic squamous cell carcinoma of the lung who developed severe TD when treated with chlorpromazine for severe hiccups. As his prognosis was only days to weeks, we were able to effectively suppress his TD with haloperidol. Hospice care emphasizes relief of suffering at the end of life, often at the expense of attention to long-range adverse effects, and this approach may be a viable management strategy for patients with TD and very limited prognosis.     

Admissions to a public residential facility for individuals with developmental disabilities: Change in neuroleptic drug use and tardive dyskinesia

Two studies were conducted to assess the change in neuroleptic medication dosages and prevalence of tardive dyskinesia (TD) in new admissions to three California Developmental Centers. The first study involved 636 admissions into Fairview, Porterville, and Sonoma Developmental Centers. Neuroleptic medication use was recorded at admission and one year later. Over that period of time, dose and prevalence of neuroleptic use was found to decrease dramatically. The second study investigated the existence of possible side effects associated with the withdrawal from neuroleptic medication. Persons with developmental disabilities (n=43) admitted to Fairview Developmental Center were examined at admission and every 8 weeks thereafter for the presence of TD. Daily neuroleptic dosages were recorded on five examination dates as well as at admission. Ten months after admission, subjects were grouped on the basis of neuroleptic medication status (withdrawn, reduced, no change). TD was manifested in 63% of the subjects in the completely withdrawn group, 29% of the subjects in the reduced group, and 10% of the subjects in the maintenance group. These studies indicate that new admissions to public residential facilities are likely to be receiving neuroleptic medication, that systematic evaluation will reslts in a majority being withdrawn from medication and that withdrawal TD will develop in most cases.     

Establishment of interrater reliability for a nursing Extrapyramidal Side Effects (EPS) Assessment Scale

Many patients who receive antipsychotic medications experience dystonia, akinesia, dyskinesia, and akathisia, collectively called Extrapyramidal Symptom Side Effects (EPS). The purpose of this study was to establish interrater reliability for a Nursing EPS Assessment Scale developed to focus on all four symptom areas. Twenty RNs and 12 patients participated in the instrument development studies. After several revisions, interrater reliability significance was demonstrated at the 0.01 level. It was concluded that the Nursing EPS Assessment Scale possessed good interrater reliability for nursing assessment of EPS.