Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial
TL;DR: Pimavanserin was well tolerated with no significant safety concerns or worsening of motor function and may benefit patients with Parkinson's disease psychosis for whom few other treatment options exist.
About: This article is published in The Lancet.The article was published on 2014-02-08. It has received 527 citations till now. The article focuses on the topics: Pimavanserin & Placebo.
Citations
More filters
Newcastle University1, University of Sydney2, Mayo Clinic3, National Institutes of Health4, University of Pennsylvania5, Houston Methodist Hospital6, Veterans Health Administration7, Stavanger University Hospital8, University of Exeter9, King's College London10, Van Andel Institute11, Nagoya University12, Rush University Medical Center13, Harvard University14, Columbia University15, University College London16, University of North Carolina at Chapel Hill17, University of Barcelona18, University of Washington19, Thomas Jefferson University20, Cleveland Clinic21, Khalifa University22, University of California, San Diego23, Stanford University24, University of Strasbourg25, University of Michigan26, United States Department of Veterans Affairs27, University of Chieti-Pescara28
TL;DR: The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade.
Abstract: The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.
2,558 citations
TL;DR: Strong evidence supports using levodopa and dopamine agonists for motor symptoms at all stages of Parkinson disease, and other therapies for motor and nonmotor features is less well established.
Abstract: Importance Parkinson disease is the second most common neurodegenerative disease worldwide. Although no available therapies alter the underlying neurodegenerative process, symptomatic therapies can improve patient quality of life. Objective To provide an evidence-based review of the initial pharmacological management of the classic motor symptoms of Parkinson disease; describe management of medication-related motor complications (such as motor fluctuations and dyskinesia), and other medication adverse effects (nausea, psychosis, and impulse control disorders and related behaviors); and discuss the management of selected nonmotor symptoms of Parkinson disease, including rapid eye movement sleep behavior disorder, cognitive impairment, depression, orthostatic hypotension, and sialorrhea. Evidence Review References were identified using searches of PubMed between January 1985 and February 2014 for English-language human studies and the full database of the Cochrane Library. The classification of studies by quality (classes I-IV) was assessed using the levels of evidence guidelines from the American Academy of Neurology and the highest-quality data for each topic. Results Although levodopa is the most effective medication available for treating the motor symptoms of Parkinson disease, in certain instances (eg, mild symptoms, tremor as the only or most prominent symptom, aged Conclusions and Relevance Strong evidence supports using levodopa and dopamine agonists for motor symptoms at all stages of Parkinson disease. Dopamine agonists and drugs that block dopamine metabolism are effective for motor fluctuations and clozapine is effective for hallucinations. Cholinesterase inhibitors may improve symptoms of dementia and antidepressants and pramipexole may improve depression. Evidence supporting other therapies for motor and nonmotor features is less well established.
1,120 citations
TL;DR: Patients experiencing complications, such as worsening symptoms and functional impairment when a medication dose wears off ("off periods"), medication-resistant tremor, and dyskinesias, benefit from advanced treatments such as therapy with levodopa-carbidopa enteral suspension or deep brain stimulation.
Abstract: Importance Parkinson disease is the most common form of parkinsonism, a group of neurological disorders with Parkinson disease–like movement problems such as rigidity, slowness, and tremor. More than 6 million individuals worldwide have Parkinson disease. Observations Diagnosis of Parkinson disease is based on history and examination. History can include prodromal features (eg, rapid eye movement sleep behavior disorder, hyposmia, constipation), characteristic movement difficulty (eg, tremor, stiffness, slowness), and psychological or cognitive problems (eg, cognitive decline, depression, anxiety). Examination typically demonstrates bradykinesia with tremor, rigidity, or both. Dopamine transporter single-photon emission computed tomography can improve the accuracy of diagnosis when the presence of parkinsonism is uncertain. Parkinson disease has multiple disease variants with different prognoses. Individuals with a diffuse malignant subtype (9%-16% of individuals with Parkinson disease) have prominent early motor and nonmotor symptoms, poor response to medication, and faster disease progression. Individuals with mild motor-predominant Parkinson disease (49%-53% of individuals with Parkinson disease) have mild symptoms, a good response to dopaminergic medications (eg, carbidopa-levodopa, dopamine agonists), and slower disease progression. Other individuals have an intermediate subtype. For all patients with Parkinson disease, treatment is symptomatic, focused on improvement in motor (eg, tremor, rigidity, bradykinesia) and nonmotor (eg, constipation, cognition, mood, sleep) signs and symptoms. No disease-modifying pharmacologic treatments are available. Dopamine-based therapies typically help initial motor symptoms. Nonmotor symptoms require nondopaminergic approaches (eg, selective serotonin reuptake inhibitors for psychiatric symptoms, cholinesterase inhibitors for cognition). Rehabilitative therapy and exercise complement pharmacologic treatments. Individuals experiencing complications, such as worsening symptoms and functional impairment when a medication dose wears off (“off periods”), medication-resistant tremor, and dyskinesias, benefit from advanced treatments such as therapy with levodopa-carbidopa enteral suspension or deep brain stimulation. Palliative care is part of Parkinson disease management. Conclusions and Relevance Parkinson disease is a heterogeneous disease with rapidly and slowly progressive forms. Treatment involves pharmacologic approaches (typically with levodopa preparations prescribed with or without other medications) and nonpharmacologic approaches (such as exercise and physical, occupational, and speech therapies). Approaches such as deep brain stimulation and treatment with levodopa-carbidopa enteral suspension can help individuals with medication-resistant tremor, worsening symptoms when the medication wears off, and dyskinesias.
1,071 citations
TL;DR: To update evidence‐based medicine recommendations for treating nonmotor symptoms in Parkinson's disease, the World Health Organization (WHO) selected Austria as a preferred destination for research and clinical trials.
Abstract: Objective
To update evidence‐based medicine recommendations for treating nonmotor symptoms in Parkinson's disease (PD).
527 citations
Cites background from "Pimavanserin for patients with Park..."
...5%), but without a unifying pattern and as such it is difficult to interpret these as drug related.(29) Nevertheless, the FDA has very recently conducted an evaluation of available information about pimavanserin after the publication of reports of postmarketing adverse events....
[...]
...” Pimavanserin, a selective serotonin 5-HT2A inverse agonist without dopaminergic, adrenergic, histaminergic, or muscarinic affinity, was evaluated in 2 level I studies.(3,29) Although the larger high-quality study had a positive outcome for antipsychotic efficacy,(29) the smaller low-quality study reported a negative outcome for the primary antipsychotic endpoint,(3) although there were several significant antipsychotic effects in the active arm....
[...]
CEU San Pablo University1, University of Marburg2, National and Kapodistrian University of Athens3, Rush University Medical Center4, Toronto Western Hospital5, University of Toronto6, University of Pennsylvania7, Newcastle University8, University of New South Wales9, University of Sydney10, Peking Union Medical College11, Centre national de la recherche scientifique12, Columbia University13, University of Paris14, Aarhus University15, UCL Institute of Neurology16, National Institutes of Health17, Emory University18, University of California, San Francisco19, San Francisco VA Medical Center20, Veterans Health Administration21, Erasmus University Medical Center22, Baylor College of Medicine23, University of Kiel24, Hebrew University of Jerusalem25, University of Barcelona26, Columbia University Medical Center27, McGill University28, University of Alabama at Birmingham29, Northwestern University30, Icahn School of Medicine at Mount Sinai31, University of Perugia32, Vancouver Coastal Health33, University of British Columbia34
TL;DR: This multiple‐author article provides a historical state‐of‐the‐art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease.
Abstract: This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.
523 citations
Cites background from "Pimavanserin for patients with Park..."
...A new antipsychotic, pimavanserin (a selective 5HT2A inverse agonist) was recently approved in the United States specifically for PD psychosis.(59) All antipsychotics, including pimavanserin, carry a black box warning for increased mortality, a finding first reported in general dementia patients and more recently in PD....
[...]
References
More filters
TL;DR: The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported, and these observations call into question current concepts of Parkinson's Disease as a single distinct morbid entity.
Abstract: Few detailed clinico-pathological correlations of Parkinson's disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer's disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson's disease as a single distinct morbid entity.
9,411 citations
TL;DR: The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time.
Abstract: We developed a new instrument, the Neuropsychiatric Inventory (NPI), to assess 10 behavioral disturbances occurring in dementia patients: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, and aberrant motor activity. The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. Both the frequency and the severity of each behavior are determined. Information for the NPI is obtained from a caregiver familiar with the patient's behavior. Studies reported here demonstrate the content and concurrent validity as well as between-rater, test-retest, and internal consistency reliability; the instrument is both valid and reliable. The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time.
6,662 citations