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      Neuropsychiatric Disease and Treatment (submit here)

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      Atypical antipsychotics for Parkinson’s disease psychosis: a systematic review and meta-analysis

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          Abstract

          Purpose

          To assess the present evidence regarding the efficiency, safety, and potential risks of pharmacotherapy used for Parkinson’s disease psychosis (PDPsy) treatment.

          Patients and methods

          We searched the following databases: PubMed, the Cochrane Library, ISI Web of Science, and Embase using the following terms: atypical antipsychotics, pimavanserin, olanzapine, quetiapine, clozapine, Parkinson’s disease and psychosis. We systematically reviewed all randomized placebo-controlled trials comparing an atypical antipsychotic with a placebo.

          Results

          A total of 13 randomized placebo-controlled trials for a total 1142 cases were identified involving pimavanserin (n=4), clozapine (n=2), olanzapine (n=3), and quetiapine (n=4). For each atypical antipsychotic, a descriptive synthesis and meta-analyses was presented. Pimavanserin was associated with a significant improvement in psychotic symptoms compared to a placebo without worsening motor function. Clozapine was efficacious in alleviating psychotic symptoms and did not exacerbate motor function either. Quetiapine and Olanzapine did not demonstrate significant differences in reducing psychotic symptoms but may aggravate motor function.

          Conclusions

          There is strong evidence that pimavanserin is effective for the treatment of PDPsy. Clozapine is also recommended but should be used with caution due to its side effects. In the future, more well-designed randomized controlled trials (RCTs) are needed to confirm and update the findings reported in this meta-analysis.

          Most cited references37

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          The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration

          Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
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            Estimating the mean and variance from the median, range, and the size of a sample

            Background Usually the researchers performing meta-analysis of continuous outcomes from clinical trials need their mean value and the variance (or standard deviation) in order to pool data. However, sometimes the published reports of clinical trials only report the median, range and the size of the trial. Methods In this article we use simple and elementary inequalities and approximations in order to estimate the mean and the variance for such trials. Our estimation is distribution-free, i.e., it makes no assumption on the distribution of the underlying data. Results We found two simple formulas that estimate the mean using the values of the median (m), low and high end of the range (a and b, respectively), and n (the sample size). Using simulations, we show that median can be used to estimate mean when the sample size is larger than 25. For smaller samples our new formula, devised in this paper, should be used. We also estimated the variance of an unknown sample using the median, low and high end of the range, and the sample size. Our estimate is performing as the best estimate in our simulations for very small samples (n ≤ 15). For moderately sized samples (15 70), the formula range/6 gives the best estimator for the standard deviation (variance). We also include an illustrative example of the potential value of our method using reports from the Cochrane review on the role of erythropoietin in anemia due to malignancy. Conclusion Using these formulas, we hope to help meta-analysts use clinical trials in their analysis even when not all of the information is available and/or reported.
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              Diagnostic criteria for psychosis in Parkinson's disease: report of an NINDS, NIMH work group.

              There are no standardized diagnostic criteria for psychosis associated with Parkinson's disease (PDPsy). As part of an NIH sponsored workshop, we reviewed the existing literature on PDPsy to provide criteria that distinguish PDPsy from other causes of psychosis. Based on these data, we propose provisional criteria for PDPsy in the style of the Diagnostic and Statistical Manual of Mental Disorders IV-TR. PDPsy has a well-characterized temporal and clinical profile of hallucinations and delusions, which is different than the pattern seen in other psychotic disorders such as substance induced psychosis or schizophrenia. PDPsy is associated with a poor prognosis of chronic psychosis, nursing home placement, and death. Medications used to treat Parkinson's disease (PD) contribute to PDPsy but may not be sufficient or necessary contributors to PDPsy. PDPsy is associated with Lewy bodies pathology, imbalances of monoaminergic neurotransmitters, and visuospatial processing deficits. These findings suggest that PDPsy may result from progression of the disease process underlying PD, rather than a comorbid psychiatric disorder or drug intoxication. PDPsy is not adequately described by existing criteria for psychotic disorders. We established provisional diagnostic criteria that define a constellation of clinical features not shared by other psychotic syndromes. The criteria are inclusive and contain descriptions of the full range of characteristic symptoms, chronology of onset, duration of symptoms, exclusionary diagnoses, and associated features such as dementia. These criteria require validation and may be refined, but form a starting point for studies of the epidemiology and pathophysiology of PDPsy, and are a potential indication for therapy development.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                NDT
                neurodist
                Neuropsychiatric Disease and Treatment
                Dove
                1176-6328
                1178-2021
                29 July 2019
                2019
                : 15
                : 2137-2149
                Affiliations
                [1 ]Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University , Guangzhou 510120, People’s Republic of China
                [2 ]Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute , Guangzhou 510080, Guangdong Province, People’s Republic of China
                [3 ]Department of Neurology, Guangzhou First Municipal People’s Hospital, Guangzhou Medical University, Guangzhou-Birmingham University Brain and Cognition Center , Guangzhou 510180, People’s Republic of China
                [4 ]Department of Neurology, The Sixth Affiliated Hospital Sun Yat-Sen University , Guangzhou 510440, People’s Republic of China
                Author notes
                Correspondence: Zhonglin LiuDepartment of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University , No.107, Yan Jiang West Road, Guangzhou, Guangdong510120, People’s Republic of ChinaTel +86 0 208 133 2621Fax +86 0 208 133 2833Email zhonglinliu@ 123456126.com
                [*]

                These authors contributed equally to this work

                Article
                201029
                10.2147/NDT.S201029
                6677378
                31551655
                e7b3a333-a68a-4939-8bec-d6e405b459b4
                © 2019 Zhang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 10 January 2019
                : 09 June 2019
                Page count
                Figures: 6, Tables: 1, References: 45, Pages: 13
                Categories
                Original Research

                Neurology
                clinical trials systematic review/meta-analysis,psychosis,parkinson’s disease/parkinsonism

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