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Benjamin Rix Brooks - One of the best experts on this subject based on the ideXlab platform.
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PRISM: A Novel Research Tool to Assess the Prevalence of Pseudobulbar Affect Symptoms across Neurological Conditions
2016Co-Authors: Benjamin Rix Brooks, Jonathan Fellus, Daniel Kantor, David Crumpacker, All E. KayeAbstract:Background: Pseudobulbar Affect (PBA) is a neurological condition characterized by involuntary, sudden, and frequent episodes of laughing and/or crying, which can be socially disabling. Although PBA occurs secondary to many neurological conditions, with an estimated United States (US) prevalence of up to 2 million persons, it is thought to be under-recognized and undertreated. The PBA Registry Series (PRISM) was established to provide additional PBA symptom prevalence data in a large, representative US sample of patients with neurological conditions known to be associated with PBA. Methods: Participating clinicians were asked to enroll$20 consenting patients with any of 6 conditions: Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson’s disease (PD), stroke, or traumatic brain injury (TBI). Patients (or their caregivers) completed the Center for Neurologic Study2Lability Scale (CNS-LS) and an 11-point scale measuring impact of the neurological condition on the patient’s quality of life (QOL). Presence of PBA symptoms was defined as a CNS2LS score $13. Demographic data and current use of antidepressant or antipsychotic medications were also recorded. Results: PRISM enrolled 5290 patients. More than one third of patients (n = 1944; 36.7%) had a CNS-LS score $13, suggesting PBA symptoms. The mean (SD) score measuring impact of neurological condition on QOL was significantly higher (worse) in patients with CNS-LS $13 vs,13 (6.7 [2.5] vs. 4.7 [3.1], respectively; P,0.0001 two-sample t-test).
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Dextromethorphan and Quinidine for Treatment of Pseudobulbar Affect (PBA): Time Course of PBA Episode Remission (S31.007)
Neurology, 2014Co-Authors: Andrea Formella, Benjamin Rix BrooksAbstract:Objective: Evaluate time to remission of Pseudobulbar Affect (PBA) episodes in a Phase III, placebo-controlled trial of dextromethorphan and quinidine. Background: PBA is a neurological condition characterized by frequent, uncontrollable episodes of laughing and/or crying that are incongruent to the patient’s emotional state. PBA is caused by brain diseases/injuries that damage neural pathways coordinating emotional expression. The condition is socially disabling and distressing to patients and others. PBA episode remission, defined as no episodes for 蠅14 days prior to endpoint, was a secondary outcome in a 12-week, double-blind, multicenter trial of dextromethorphan and quinidine vs. placebo. This post-hoc analysis assessed time to entering remission for the FDA-approved dose of dextromethorphan 20 mg/quinidine 10 mg (DMQ-20) given twice daily vs. placebo. Design/Methods: Patients were adults with clinically significant PBA secondary to amyotrophic lateral sclerosis or multiple sclerosis. DMQ-20 and placebo were dosed once daily for week 1 and twice daily thereafter. The percentage of patients entering remission, defined as no further PBA episodes in study + minimum 14 days without episodes prior to endpoint was assessed at each study week. Results: The trial randomized 107 patients to DMQ-20 and 109 to placebo. By Week 1, 18.7% of patients on DMQ-20 and 5.5% on placebo (P=.003; chi square) had entered remission (no further PBA episodes during the study). For Week 2 (first week of twice daily dosing) these percentages were 24.3% and 7.3%, respectively (P
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PRISM: A Novel Research Tool to Assess the Prevalence of Pseudobulbar Affect Symptoms across Neurological Conditions
PloS one, 2013Co-Authors: Benjamin Rix Brooks, David W. Crumpacker, Jonathan Fellus, Daniel Kantor, Randall E. KayeAbstract:Background Pseudobulbar Affect (PBA) is a neurological condition characterized by involuntary, sudden, and frequent episodes of laughing and/or crying, which can be socially disabling. Although PBA occurs secondary to many neurological conditions, with an estimated United States (US) prevalence of up to 2 million persons, it is thought to be under-recognized and undertreated. The PBA Registry Series (PRISM) was established to provide additional PBA symptom prevalence data in a large, representative US sample of patients with neurological conditions known to be associated with PBA. Methods Participating clinicians were asked to enroll ≥20 consenting patients with any of 6 conditions: Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson’s disease (PD), stroke, or traumatic brain injury (TBI). Patients (or their caregivers) completed the Center for Neurologic Study−Lability Scale (CNS-LS) and an 11-point scale measuring impact of the neurological condition on the patient’s quality of life (QOL). Presence of PBA symptoms was defined as a CNS−LS score ≥13. Demographic data and current use of antidepressant or antipsychotic medications were also recorded. Results PRISM enrolled 5290 patients. More than one third of patients (n = 1944; 36.7%) had a CNS-LS score ≥13, suggesting PBA symptoms. The mean (SD) score measuring impact of neurological condition on QOL was significantly higher (worse) in patients with CNS-LS ≥13 vs
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Pseudobulbar Affect in Stroke in Statesmen: The Peculiar Case of Winston Spencer Churchill (P04.003)
Neurology, 2012Co-Authors: Benjamin Rix BrooksAbstract:Objective: To review the evidence that Winston Spencer Churchill had Pseudobulbar Affect as a consequence of his stroke in 1953. Background Few statesmen have had as open a review of his medical condition as Winston Spencer Churchill who was Prime Minister of the United Kingdom. He had a possible stroke in 1949. The stroke that was associated with emotional lability occurred in 1953 with clinical details related in 1] W. Russell Brain, "Encounters with Winston Churchill," Medical History, vol. 44, 2000, 3-20, 2) Richard Gordon, An Alarming History of Famous and Difficult Patients. New York: St. Martin9s Press, 1997, 3) Richard Lovell, Churchill9s Doctor: A Biography of Lord Moran, New York: Parthenon, 1993 and 4) Lord Moran, Churchill: The Struggle for Survival 1945-60. Design/Methods: Churchill was examined 9 times by Lord Brain following his stroke in 1953. By one month after the stroke his dysarthria and dysphagia had improved but Churchill had loss of emotional control which had worsened as other deficits improved. Churchill noticed that he was "always rather blubbery". Multiple sources identified this clinical change and felt that Churchill could not attend upcoming government and political events lest the public learn of his stroke. The only treatment mentioned for this condition and Churchill9s fatigue was repeated doses of benzedrine. Results: Descriptions of emotionality and its potential political consequences were found 9 times in Lord Moran9s accounts and 4 times in Lord Brain9s account. Other sources alluded to these changes but only the neurologist and treating physician accounts gave appropriate descriptive elements to establish the diagnosis based on historical records. Conclusions: Churchill9s stroke related Pseudobulbar Affect was described in several medical and non-medical sources. It9s late onset post stroke and resolution remains the best studied example of Pseudobulbar Affect in a public statesman to date. Disclosure: Dr. Brooks has received personal compensation for activities with Avanir Pharmaceuticals, Bayer Healthcare Pharmaceuticals, Biogen Idec, Genentech, Inc., and Teva Neuroscience. Dr. Brooks has received research support from Avanir Pharmaceuticals, Biogen Idec, NINDS, Novartis, and Teva Neuroscience.
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Dextromethorphan Plus Ultra Low-Dose Quinidine Reduces Pseudobulbar Affect
Annals of neurology, 2010Co-Authors: Erik P. Pioro, Benjamin Rix Brooks, Ronald A. Thisted, Daniel Wynn, Randolph B. Schiffer, Jeffrey L. Cummings, Adrian Hepner, Randall E. KayeAbstract:Objective: To evaluate dextromethorphan combined with ultra low-dose quinidine (DMq) for treating Pseudobulbar Affect (PBA) in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). Methods: In a 12-week randomized, double-blind trial, ALS and MS patients with clinically significant PBA (a baseline score � 13 on the Center for Neurologic Studies–Lability Scale [CNS-LS]) were maintained, twice daily, on placebo, DMq at 30/10mg (DMq-30), or DMq at 20/10mg (DMq-20). Results: In 326 randomized patients (of whom 283, or 86.8%, completed the study), the PBA-episode daily rate was 46.9% (p < 0.0001) lower for DMq-30 than for placebo and 49.0% (p < 0.0001) lower for DMq-20 than for placebo by longitudinal negative binomial regression, the prespecified primary analysis. Mean CNS-LS scores decreased by 8.2 points for DMq-30 and 8.2 for DMq-20, vs 5.7 for placebo (p¼ 0.0002 and p¼ 0.0113, respectively). Other endpoints showing statistically significant DMq benefit included, for both dosage levels, the likelihood of PBA remission during the final 14 days and, for the higher dosage, improvement on measures of social functioning and mental health. Both dosages were safe and well tolerated. Interpretation: DMq markedly reduced PBA frequency and severity, decreasing the condition’s detrimental impact on a patient’s life, with satisfactory safety and high tolerability. The findings expand the clinical evidence that DMq may be an important treatment for patients suffering from the socially debilitating symptoms of PBA. ANN NEUROL 2010;00:000–000
Ariel Miller - One of the best experts on this subject based on the ideXlab platform.
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Pseudobulbar Affect: the spectrum of clinical presentations, etiologies and treatments
Expert review of neurotherapeutics, 2011Co-Authors: Ariel Miller, Hillel Pratt, Randolph B. SchifferAbstract:Pseudobulbar Affect (PBA) consists of uncontrollable outbursts of laughter or crying inappropriate to the patient's external circumstances and incongruent with the patient's internal emotional state. Recent data suggest disruption of cortico-pontine-cerebellar circuits, reducing the threshold for motor expression of emotion. Disruption of the microcircuitry of the cerebellum itself may likewise impair its ability to act as a gate-control for emotional expression. Current evidence also suggests that serotonergic and glutamatergic neurotransmission play key roles. Although antidepressants have shown benefit, the supportive clinical data have often derived from small numbers of patients and unvalidated measures of PBA severity. Dextromethorphan/quinidine, the first FDA-approved PBA medication, is a novel therapy with antiglutamatergic actions. As life expectancy lengthens and the neurologic settings of PBA become more common, the need for treatment can be expected to increase.
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Brain responses to verbal stimuli among multiple sclerosis patients with Pseudobulbar Affect.
Journal of the neurological sciences, 2008Co-Authors: Guy Haiman, Hillel Pratt, Ariel MillerAbstract:To characterize the brain activity and associated cortical structures involved in Pseudobulbar Affect (PBA), a condition characterized by uncontrollable episodes of emotional lability in patients with multiple sclerosis (MS). Behavioral responses and event related potentials (ERP) in response to subjectively significant and neutral verbal stimuli were recorded from 33 subjects in 3 groups: 1) MS patients with PBA (MS+PBA); 2) MS patients without PBA (MS); 3) Healthy control subjects (HC). Statistical non-parametric mapping comparisons of ERP source current density distributions between groups were conducted separately for subjectively significant and for neutral stimuli. Behavioral responses showed more impulsive performance in patients with PBA. As expected, almost all ERP waveform comparisons between the MS groups and controls were significant. Source analysis indicated significantly distinct activation in MS+PBA in the vicinity of the somatosensory and motor areas in response to neutral stimuli, and at pre-motor and supplementary motor areas in response to subjectively significant stimuli. Both subjectively significant and neutral stimuli evoked higher current density in MS+PBA compared to both other groups. PBA of MS patients involves cortical structures related to sensory-motor and emotional processing, in addition to overactive involvement of motor cortical areas in response to neutral stimuli. These results may suggest that a 'disinhibition' of a "gate control"-type mechanism for emotional expression may lead to the lower emotional expression threshold of Pseudobulbar Affect.
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Brain responses to verbal stimuli among multiple sclerosis patients with Pseudobulbar Affect.
Journal of the Neurological Sciences, 2008Co-Authors: Guy Haiman, Hillel Pratt, Ariel MillerAbstract:Abstract Purpose To characterize the brain activity and associated cortical structures involved in Pseudobulbar Affect (PBA), a condition characterized by uncontrollable episodes of emotional lability in patients with multiple sclerosis (MS). Methods Behavioral responses and event related potentials (ERP) in response to subjectively significant and neutral verbal stimuli were recorded from 33 subjects in 3 groups: 1) MS patients with PBA (MS + PBA); 2) MS patients without PBA (MS); 3) Healthy control subjects (HC). Statistical non-parametric mapping comparisons of ERP source current density distributions between groups were conducted separately for subjectively significant and for neutral stimuli. Results Behavioral responses showed more impulsive performance in patients with PBA. As expected, almost all ERP waveform comparisons between the MS groups and controls were significant. Source analysis indicated significantly distinct activation in MS + PBA in the vicinity of the somatosensory and motor areas in response to neutral stimuli, and at pre-motor and supplementary motor areas in response to subjectively significant stimuli. Both subjectively significant and neutral stimuli evoked higher current density in MS + PBA compared to both other groups. Conclusions PBA of MS patients involves cortical structures related to sensory-motor and emotional processing, in addition to overactive involvement of motor cortical areas in response to neutral stimuli. Significance These results may suggest that a ‘disinhibition’ of a “gate control”-type mechanism for emotional expression may lead to the lower emotional expression threshold of Pseudobulbar Affect.
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Therapeutic use of dextromethorphan: key learnings from treatment of Pseudobulbar Affect.
Journal of the neurological sciences, 2007Co-Authors: Ariel Miller, Hillel PanitchAbstract:A variety of neurological conditions and disease states are accompanied by Pseudobulbar Affect (PBA), an emotional disorder characterized by uncontrollable outbursts of laughing and crying. The causes of PBA are unclear but may involve lesions in neural circuits regulating the motor output of emotional expression. Several agents used in treating other psychiatric disorders have been applied in the treatment of PBA with some success but data are limited and these agents are associated with unpleasant side effects due to nonspecific activity in diffuse neural networks. Dextromethorphan (DM), a widely used cough suppressant, acts at receptors in the brainstem and cerebellum, brain regions implicated in the regulation of emotional output. The combination of DM and quinidine (Q), an enzyme inhibitor that blocks DM metabolism, has recently been tested in phase III clinical trials in patients with multiple sclerosis and amyotrophic lateral sclerosis and was both safe and effective in palliating PBA symptoms. In addition, clinical studies pertaining to the safety and efficacy of DM/Q in a variety of neurological disease states are ongoing.
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Pseudobulbar Affect in multiple sclerosis: toward the development of innovative therapeutic strategies.
Journal of the neurological sciences, 2006Co-Authors: Ariel MillerAbstract:Pseudobulbar Affect (PBA), a condition involving involuntary and uncontrollable episodes of crying and/or laughing, occurs frequently in patients with a variety of neurological disorders, including amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury, dementia including Alzheimer's disease, and multiple sclerosis (MS). Although PBA results in considerable distress for patients and caretakers, it is underrecognized and undertreated. Agents used to treat psychiatric disorders--particularly tricyclic antidepressants and selective serotonin reuptake inhibitors--are useful in alleviating PBA, but act on diffuse neural networks rather than targeting those involved in emotional motor expression. As a result of their nonspecific activity, these agents are associated with a range of unwanted effects that preclude many patients from using them. Dextromethorphan, a common cough suppressant, specifically targets sigma(1) receptors concentrated in the brainstem and cerebellum, thus providing the possibility of targeting regions implicated in emotional expression. When administered in a fixed combination with quinidine, dextromethorphan is effective in treating PBA in patients with ALS, and preliminary results suggest that this therapy also is effective in treating MS-related PBA.
Charles Yonan - One of the best experts on this subject based on the ideXlab platform.
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Identification of Pseudobulbar Affect symptoms in the nursing home setting: Development and assessment of a screening tool.
Geriatric nursing (New York N.Y.), 2017Co-Authors: Carrie Allen, Barbara J. Zarowitz, Terrence O'shea, Edward L. Peterson, Charles Yonan, Fanta WatermanAbstract:Abstract Pseudobulbar Affect (PBA) is a neurologic condition characterized by involuntary outbursts of crying and/or laughing disproportionate to patient mood or social context. Although an estimated 9% of nursing home residents have symptoms suggestive of PBA, they are not routinely screened. Our goal was to develop an electronic screening tool based upon characteristics common to nursing home residents with PBA identified through medical record data. Nursing home residents with PBA treated with dextromethorphan hydrobromide/quinidine sulfate (n = 140) were compared to age-, gender-, and dementia-diagnosis-matched controls without PBA or treatment (n = 140). Comparative categories included diagnoses, medication use and symptom documentation. Using a multivariable regression and best decision rule analysis, we found PBA in nursing home residents was associated with chart documentation of uncontrollable crying, presence of a neurologic disorder (e.g., Parkinson's disease), or by the documented presence of at least 2 of the following: stroke, severe cognitive impairment, and schizophrenia. Based on these risk factors, an electronic screening tool was created.
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an open label study to assess safety tolerability and effectiveness of dextromethorphan quinidine for Pseudobulbar Affect in dementia prism ii results
Cns Spectrums, 2016Co-Authors: Rachelle S. Doody, Charles Yonan, Paul Shin, Fred Ledon, Andrew J. Cutler, Charles S. Davis, Stephen Damico, Joao SiffertAbstract:Background Dextromethorphan (DM)/quinidine (Q) is an approved treatment for Pseudobulbar Affect (PBA) based on trials in amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness and tolerability for PBA secondary to dementia, stroke, or traumatic brain injury; dementia cohort results are reported. Methods This was an open-label, multicenter, 90 day trial; patients received DM/Q 20/10 mg twice daily. Primary outcome was change in Center for Neurologic Study–Lability Scale (CNS-LS) score. Secondary outcomes included PBA episode count and Clinical and Patient/Caregiver Global Impression of Change scores with respect to PBA (CGI-C/PGI-C). Results 134 patients were treated. CNS-LS improved by a mean (SD) of 7.2 (6.0) points at Day 90/Endpoint ( P P Conclusions DM/Q significantly reduced PBA symptoms in patients with dementia; reported adverse events were consistent with the known safety profile of DM/Q. Trial Registration clinicaltrials.gov identifier: NCT01799941.
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Abstract 107: Dextromethorphan/Quinidine for Treatment of Pseudobulbar Affect Secondary to Stroke: Results from the PRISM-II Study
Stroke, 2016Co-Authors: Richard D. Zorowitz, Charles Yonan, David Alexander, Paul Shin, Fred Ledon, Andrea E. Formella, Charles E. Davis, Joao SiffertAbstract:Introduction: Pseudobulbar Affect (PBA) is characterized by sudden, frequent, uncontrollable laughing/crying episodes that are out of proportion or disconnected from mood or social context. PRISM-I...
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abstract 107 dextromethorphan quinidine for treatment of Pseudobulbar Affect secondary to stroke results from the prism ii study
Stroke, 2016Co-Authors: Richard D. Zorowitz, Charles Yonan, David Alexander, Paul Shin, Fred Ledon, Andrea E. Formella, Charles E. Davis, Joao SiffertAbstract:Introduction: Pseudobulbar Affect (PBA) is characterized by sudden, frequent, uncontrollable laughing/crying episodes that are out of proportion or disconnected from mood or social context. PRISM-I...
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Prevalence of Pseudobulbar Affect symptoms and clinical correlates in nursing home residents.
International journal of geriatric psychiatry, 2015Co-Authors: Kevin T. Foley, R. Tamara Konetzka, Anthony Bunin, Charles YonanAbstract:Objective Pseudobulbar Affect (PBA) is a neurological disorder of emotional expression, characterized by uncontrollable episodes of crying or laughing in patients with certain neurological disorders Affecting the brain. The purposes of this study were to estimate the prevalence of PBA in US nursing home residents and examine the relationship between PBA symptoms and other clinical correlates, including the use of psychopharmacological medications. Methods A retrospective study was conducted between 2013 and 2014 with a convenience sample of residents from nine Michigan nursing homes. Chronic-care residents were included in the “predisposed population” if they had a neurological disorder Affecting the brain and no evidence of psychosis, delirium, or disruptive behavior (per chart review). Residents were screened for PBA symptoms by a geropsychologist using the Center for Neurologic Study-Lability Scale (CNS-LS). Additional clinical information was collected using a diagnostic evaluation checklist and the most recent Minimum Data Set 3.0 assessment. Results Of 811 residents screened, complete data were available for 804, and 412 (51%) met the criteria for the “predisposed population.” PBA symptom prevalence, based on having a CNS-LS score ≥13, was 17.5% in the predisposed population and 9.0% among all nursing home residents. Those with PBA symptoms were more likely to have a documented mood disorder and be using a psychopharmacological medication, including antipsychotics, than those without PBA symptoms. Conclusions Pseudobulbar Affect symptoms were present in 17.5% of nursing home residents with neurological conditions, and 9.0% of residents overall. Increasing awareness and improving diagnostic accuracy of PBA may help optimize treatment. Copyright © 2015 John Wiley & Sons, Ltd.
Walter G. Bradley - One of the best experts on this subject based on the ideXlab platform.
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Pseudobulbar Affect: burden of illness in the USA.
Advances in therapy, 2012Co-Authors: Jennifer Colamonico, Andrea Formella, Walter G. BradleyAbstract:Introduction Pseudobulbar Affect (PBA) is characterized by involuntary and uncontrollable laughing and/or crying episodes, occurring secondary to neurological disease or injury. The impact of PBA on social and occupational function, health status, quality of life (QOL), and quality of relationships (QOR) is not well studied.
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Pseudobulbar Affect: an under-recognized and under-treated neurological disorder
Advances in Therapy, 2011Co-Authors: Susan S. Work, Walter G. Bradley, Jennifer A. Colamonico, Randall E. KayeAbstract:Introduction Pseudobulbar Affect (PBA) is a neurologic syndrome of emotional Affect disinhibition, characterized by uncontrollable, exaggerated, and often inappropriate emotional outbursts, which may cause severe distress, embarrassment, and social dysfunction. However, the US prevalence of PBA remains unknown. Methods An online survey was conducted primarily to estimate the US prevalence of PBA in patients with the six most commonly associated conditions: Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson’s disease, stroke, and traumatic brain injury. Invitations to participate were randomly sent online to adults (aged ≥18 years) registered in the Harris Poll Online Panel who were patients or belonged to a household with a patient diagnosed with one of the six conditions (identified through previous screening by Harris Interactive). Participants were screened for PBA using the Pathological Laughing and Crying Scale (PLACS) and the Center for Neurologic Study-Lability Scale (CNS-LS). PBA estimates were made using a cut-off score of ≥13 on the PLACS and two different cut-off thresholds on the CNS-LS, a lower one of ≥13 and a more rigorous one of ≥21. Existing US prevalence data for the six underlying conditions were used to estimate US prevalence of PBA. Results Of 38,000 individuals invited to participate, 8876 responded (23%) and 2318 (26%) completed the questionnaire. Mean prevalence of PBA across all six conditions was 10.1%, 9.4%, and 37.5% with the PLACS ≥13, CNS-LS ≥21, and CNS-LS ≥13 thresholds, respectively. Using disease population estimates from government agencies and professional organizations, the estimated US population with PBA ranged from 1.8 to 7.1 million. Among patients who discussed their laughing and/or crying episodes with a physician, 41% were diagnosed, and about half received a medication for their episodes. Conclusions The overall prevalence of PBA was estimated to be about 10% across these commonly associated underlying neurological conditions and appears to be under-recognized.
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Pseudobulbar Affect: An under-recognized and under-treated neurological disorder
Advances in therapy, 2011Co-Authors: Susan S. Work, Jennifer Colamonico, Walter G. Bradley, Randall E. KayeAbstract:Introduction Pseudobulbar Affect (PBA) is a neurologic syndrome of emotional Affect disinhibition, characterized by uncontrollable, exaggerated, and often inappropriate emotional outbursts, which may cause severe distress, embarrassment, and social dysfunction. However, the US prevalence of PBA remains unknown.
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treatment of Pseudobulbar Affect in als with dextromethorphan quinidine a randomized trial
Neurology, 2004Co-Authors: Benjamin Rix Brooks, Walter G. Bradley, Ronald A. Thisted, Stanley H. Appel, Richard K. Olney, James Berg, Laura E. Pope, Richard A SmithAbstract:Background: Patients with ALS commonly exhibit Pseudobulbar Affect. Methods: The authors conducted a multicenter, randomized, double-blind, controlled, parallel, three-arm study to test a defined combination of dextromethorphan hydrobromide (DM) and quinidine sulfate (Q) (AVP-923) for the treatment of Pseudobulbar Affect in ALS. Q inhibits the rapid first-pass metabolism of DM. The effects of AVP-923 (30 mg of DM plus 30 mg of Q) given twice daily for 28 days were compared with those of its components. Patients were evaluated on days 1, 15, and 29. The primary efficacy variable was the change from baseline in the Center for Neurologic Study Lability Scale (CNS-LS) score. Secondary efficacy variables were laughing/crying episode rates and changes in Visual Analog Scales for Quality of Life (QOL) and Relationships (QOR). Efficacy was evaluated in intention-to-treat subjects who were not poor metabolizers of DM (n = 65 for AVP-923, n = 30 for DM, and n = 34 for Q). Safety was assessed in all randomized subjects (n = 140). Results: AVP-923 patients experienced 3.3-point greater improvements in CNS-LS than DM patients ( p = 0.001) and 3.7-point greater improvements than Q patients ( p p Conclusions: AVP-923 palliates Pseudobulbar Affect in ALS. Overall benefits of treatment are reflected in fewer episodes of crying and laughing and improvements in overall quality of life and quality of relationships.
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Treatment of Pseudobulbar Affect in ALS with dextromethorphan/quinidine: a randomized trial.
Neurology, 2004Co-Authors: Benjamin Rix Brooks, Walter G. Bradley, Ronald A. Thisted, Stanley H. Appel, Richard K. Olney, James Berg, Laura E. Pope, Richard A SmithAbstract:Background: Patients with ALS commonly exhibit Pseudobulbar Affect. Methods: The authors conducted a multicenter, randomized, double-blind, controlled, parallel, three-arm study to test a defined combination of dextromethorphan hydrobromide (DM) and quinidine sulfate (Q) (AVP-923) for the treatment of Pseudobulbar Affect in ALS. Q inhibits the rapid first-pass metabolism of DM. The effects of AVP-923 (30 mg of DM plus 30 mg of Q) given twice daily for 28 days were compared with those of its components. Patients were evaluated on days 1, 15, and 29. The primary efficacy variable was the change from baseline in the Center for Neurologic Study Lability Scale (CNS-LS) score. Secondary efficacy variables were laughing/crying episode rates and changes in Visual Analog Scales for Quality of Life (QOL) and Relationships (QOR). Efficacy was evaluated in intention-to-treat subjects who were not poor metabolizers of DM (n = 65 for AVP-923, n = 30 for DM, and n = 34 for Q). Safety was assessed in all randomized subjects (n = 140). Results: AVP-923 patients experienced 3.3-point greater improvements in CNS-LS than DM patients ( p = 0.001) and 3.7-point greater improvements than Q patients ( p p Conclusions: AVP-923 palliates Pseudobulbar Affect in ALS. Overall benefits of treatment are reflected in fewer episodes of crying and laughing and improvements in overall quality of life and quality of relationships.
Joao Siffert - One of the best experts on this subject based on the ideXlab platform.
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dextromethorphan quinidine for Pseudobulbar Affect following stroke safety and effectiveness in the prism ii trial
Pm&r, 2019Co-Authors: Richard D. Zorowitz, Fred Ledon, Andrea E. Formella, Charles E. Davis, David N. Alexander, Joao SiffertAbstract:Abstract Background Dextromethorphan (DM) / quinidine (Q) was approved for Pseudobulbar Affect (PBA) treatment based on efficacy and safety trials in patients with PBA caused by amyotrophic lateral sclerosis or multiple sclerosis. The PRISM II trial evaluated DM/Q as PBA treatment in patients with stroke, dementia, or traumatic brain injury. Objective To report results from the stroke cohort of PRISM II, including the Stroke Impact Scale (SIS). Design Open-label trial evaluating twice-daily DM/Q over 90 days. Study participants Adults (n = 113) with a clinical diagnosis of PBA secondary to stroke; stable psychiatric medications were allowed. Methods PRISM II was an open-label, 12-week trial enrolling adults with PBA caused by dementia, stroke (reported here), or TBI. All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at days 30 and 90. Setting 150 U.S. centers. Main Outcome Measurements Primary efficacy measure was changed from baseline to day 90 in Center for Neurologic Study–Lability Scale (CNS-LS) scores. Secondary outcomes included PBA episodes (estimated over 7 days), Clinical and Patient/Caregiver Global Impression of Change (CGI-C and PGI-C), Quality of Life–Visual Analog Scale (QOL-VAS), SIS, Patient Health Questionnaire (PHQ-9), and Mini-Mental State Examination (MMSE). Results Compared with baseline, CNS-LS scores (SD) improved by –6.2 (6.1, P Conclusions DM/Q effectively treated PBA and was associated with global and functional improvement; adverse events were consistent with the known safety profile of DM/Q.
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Dextromethorphan/Quinidine for Pseudobulbar Affect Following Stroke: Safety and Effectiveness in the PRISM II Trial.
PM & R : the journal of injury function and rehabilitation, 2018Co-Authors: Richard D. Zorowitz, Fred Ledon, Andrea E. Formella, Charles E. Davis, David N. Alexander, Joao SiffertAbstract:Abstract Background Dextromethorphan (DM) / quinidine (Q) was approved for Pseudobulbar Affect (PBA) treatment based on efficacy and safety trials in patients with PBA caused by amyotrophic lateral sclerosis or multiple sclerosis. The PRISM II trial evaluated DM/Q as PBA treatment in patients with stroke, dementia, or traumatic brain injury. Objective To report results from the stroke cohort of PRISM II, including the Stroke Impact Scale (SIS). Design Open-label trial evaluating twice-daily DM/Q over 90 days. Study participants Adults (n = 113) with a clinical diagnosis of PBA secondary to stroke; stable psychiatric medications were allowed. Methods PRISM II was an open-label, 12-week trial enrolling adults with PBA caused by dementia, stroke (reported here), or TBI. All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at days 30 and 90. Setting 150 U.S. centers. Main Outcome Measurements Primary efficacy measure was changed from baseline to day 90 in Center for Neurologic Study–Lability Scale (CNS-LS) scores. Secondary outcomes included PBA episodes (estimated over 7 days), Clinical and Patient/Caregiver Global Impression of Change (CGI-C and PGI-C), Quality of Life–Visual Analog Scale (QOL-VAS), SIS, Patient Health Questionnaire (PHQ-9), and Mini-Mental State Examination (MMSE). Results Compared with baseline, CNS-LS scores (SD) improved by –6.2 (6.1, P Conclusions DM/Q effectively treated PBA and was associated with global and functional improvement; adverse events were consistent with the known safety profile of DM/Q.
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an open label study to assess safety tolerability and effectiveness of dextromethorphan quinidine for Pseudobulbar Affect in dementia prism ii results
Cns Spectrums, 2016Co-Authors: Rachelle S. Doody, Charles Yonan, Paul Shin, Fred Ledon, Andrew J. Cutler, Charles S. Davis, Stephen Damico, Joao SiffertAbstract:Background Dextromethorphan (DM)/quinidine (Q) is an approved treatment for Pseudobulbar Affect (PBA) based on trials in amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness and tolerability for PBA secondary to dementia, stroke, or traumatic brain injury; dementia cohort results are reported. Methods This was an open-label, multicenter, 90 day trial; patients received DM/Q 20/10 mg twice daily. Primary outcome was change in Center for Neurologic Study–Lability Scale (CNS-LS) score. Secondary outcomes included PBA episode count and Clinical and Patient/Caregiver Global Impression of Change scores with respect to PBA (CGI-C/PGI-C). Results 134 patients were treated. CNS-LS improved by a mean (SD) of 7.2 (6.0) points at Day 90/Endpoint ( P P Conclusions DM/Q significantly reduced PBA symptoms in patients with dementia; reported adverse events were consistent with the known safety profile of DM/Q. Trial Registration clinicaltrials.gov identifier: NCT01799941.
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Abstract 107: Dextromethorphan/Quinidine for Treatment of Pseudobulbar Affect Secondary to Stroke: Results from the PRISM-II Study
Stroke, 2016Co-Authors: Richard D. Zorowitz, Charles Yonan, David Alexander, Paul Shin, Fred Ledon, Andrea E. Formella, Charles E. Davis, Joao SiffertAbstract:Introduction: Pseudobulbar Affect (PBA) is characterized by sudden, frequent, uncontrollable laughing/crying episodes that are out of proportion or disconnected from mood or social context. PRISM-I...
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abstract 107 dextromethorphan quinidine for treatment of Pseudobulbar Affect secondary to stroke results from the prism ii study
Stroke, 2016Co-Authors: Richard D. Zorowitz, Charles Yonan, David Alexander, Paul Shin, Fred Ledon, Andrea E. Formella, Charles E. Davis, Joao SiffertAbstract:Introduction: Pseudobulbar Affect (PBA) is characterized by sudden, frequent, uncontrollable laughing/crying episodes that are out of proportion or disconnected from mood or social context. PRISM-I...
