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      Characteristics of Patients Experiencing Extrapyramidal Symptoms or Other Movement Disorders Related to Dopamine Receptor Blocking Agent Therapy

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          Abstract

          Supplemental digital content is available in the text.

          Abstract

          Purpose/Background

          Dopamine receptor blocking agents (DRBAs), also known as antipsychotics, are medications widely used to treat a growing number of mental health diagnoses. However, their utility is limited by the potential to cause serious adverse movement reactions. Akathisia, dystonia, parkinsonism, and tardive dyskinesia (collectively known as extrapyramidal symptoms or EPSs) are associated with reduced social and occupational functioning, negative patient attitudes toward treatment, and nonadherence to pharmacotherapy. Neuroleptic malignant syndrome is a life-threatening reaction that can result from DRBA use and cause musculoskeletal dysfunction. The aim of this study is to profile patients who have developed DRBA-related movement adverse effects and identify risk factors significantly associated with each subtype of EPSs or other movement disorders (OMDs) such as neuroleptic malignant syndrome.

          Methods/Procedures

          A report of all potential DRBA-related EPSs or OMDs occurrences within a large community hospital network was generated using International Classification of Diseases, Ninth Revision ( ICD-9) and 10th Revision ( ICD-10) billing codes. Each patient encounter was manually reviewed to confirm that a documented case of DRBA-related EPSs or OMDs had indeed occurred and subsequently determine the likely causative agent(s).

          Findings/Results

          The resultant cohort of 148 patients experiencing unique DRBA-related EPS or OMD events was analyzed. The average patient was female, middle-aged, and overweight. The most common DRBAs precipitating EPSs or OMDs were haloperidol and quetiapine. In the population studied, age was significantly associated with the subtype of EPSs experienced such that those patients with akathisia and dystonia tended to be younger, whereas those with tardive dyskinesia tended to be older. Body mass index (BMI) category was also negatively correlated with the incidence of dystonia. In addition, it was observed that exposure to specific DRBAs, classes, and routes of administration significantly affected the risk of developing different subtypes of EPSs or OMDs in the study population.

          Implications/Conclusions

          To our knowledge, this is the first study to describe an association between age and BMI with the risk of akathisia and dystonia, respectively, in patients taking DRBAs. Other trends observed with age and BMI in patients developing DRBA-related EPSs support previously reported findings. Expanding the knowledge base of individual characteristics associated with the risk of developing different subtypes of EPSs or OMDs can help providers and patients anticipate and attempt to mitigate these reactions, and may ultimately improve adherence to DRBA therapy.

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          Most cited references52

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          Neuroleptic malignant syndrome.

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            Second-Generation Antipsychotics and Extrapyramidal Adverse Effects

            Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability.
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              Neuroleptic malignant syndrome: a review for neurohospitalists.

              Neuroleptic malignant syndrome (NMS) is a life-threatening idiosyncratic reaction to antipsychotic drugs characterized by fever, altered mental status, muscle rigidity, and autonomic dysfunction. It has been associated with virtually all neuroleptics, including newer atypical antipsychotics, as well as a variety of other medications that affect central dopaminergic neurotransmission. Although uncommon, NMS remains a critical consideration in the differential diagnosis of patients presenting with fever and mental status changes because it requires prompt recognition to prevent significant morbidity and death. Treatment includes immediately stopping the offending agent and implementing supportive measures, as well as pharmacological interventions in more severe cases. Maintaining vigilant awareness of the clinical features of NMS to diagnose and treat the disorder early, however, remains the most important strategy by which physicians can keep mortality rates low and improve patient outcomes.
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                Author and article information

                Journal
                J Clin Psychopharmacol
                J Clin Psychopharmacol
                JCP
                Journal of Clinical Psychopharmacology
                Lippincott Williams & Wilkins
                0271-0749
                1533-712X
                Jul-Aug 2019
                11 June 2019
                : 39
                : 4
                : 336-343
                Affiliations
                From the [* ]Department of Clinical Sciences, High Point University Fred Wilson School of Pharmacy, High Point, NC;
                []Department of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences;
                []Department of Pharmacy, Community Health Network, Indianapolis;
                [§ ]Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafayette;
                []Office of Research Administration, Community Health Network; and
                []Department of Psychiatry, Community Health Network, Indianapolis, IN.
                Author notes
                [*]Reprints: Shaina Musco, PharmD, Department of Clinical Sciences, High Point University Fred Wilson School of Pharmacy, One University Parkway, High Point, NC 27268 (e-mail: smusco@ 123456highpoint.edu ).
                Article
                JCP50729 00008
                10.1097/JCP.0000000000001061
                6594730
                31205194
                e39a841b-f6fd-4041-96dd-dd796305439d
                Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                : 27 July 2018
                : 28 April 2019
                : 28 April 2019
                Page count
                Pages: 0
                Categories
                Original Contributions
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                dopamine receptor blocking agent,antipsychotic,extrapyramidal symptom,age,body mass index

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