DOCSLIB.ORG

Wo 2008/097924 A2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Wo 2008/097924 A2 (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date (10) International Publication Number 14 August 2008 (14.08.2008) PCT WO 2008/097924 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 31/473 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY,BZ, CA, (21) International Application Number: CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, PCT/US2008/052949 EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, (22) International Filing Date: 4 February 2008 (04.02.2008) LK, LR, LS, LT, LU, LY,MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, (25) Filing Language: English PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, (26) Publication Language: English ZA, ZM, ZW (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 60/899,472 5 February 2007 (05.02.2007) US kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): AVANIR GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, PHARMACEUTICALS [US/US]; 101 Enterprise, Suite ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), 300, Aliso Viejo, CA 92656 (US). European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT,LU, LV,MC, MT, NL, (72) Inventors; and NO, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, (75) Inventors/Applicants (for US only): SIRCAR, Jagadish CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). [US/US]; 4832 Riding Ridge Road, San Diego, CA 92130 (US). KUMAR, KC, Sunil [NP/US] ; 10504 Clasico Court, Declaration under Rule 4.17: San Diego, CA 27127 (US). — of inventorship (Rule 4.17(iv)) (74) Agent: DELANEY, Karoline, A.; Knobbe, Martens, Ol- Published: son & Bear, LLP, 2040 Main Street, 14th Floor, Irvine, CA — without international search report and to be republished 92614 (US). upon receipt of that report (54) Title: PHARMACEUTICAL COMPOSITIONS COMPRISING DEXTROMETHORPHAN ANALOGS FOR THE TREAT- MENT OF NEUROLOGICAL DISORDERS (57) Abstract: Pharmaceutical compositions and methods for treating neurological disorders by administering same are provided. The compositions comprise dextromethorphan analogs. PHARMACEUTICAL COMPOSITIONS COMPRISING DEXTROMETHORPHAN ANALOGS FOR THE TREATMENT OF NEUROLOGICAL DISORDERS FIELD OF THE INVENTION [0001] Pharmaceutical compositions and methods for treating neurological disorders are provided. The compositions comprise dextromethorphan analogs. BACKGROUND OF THE INVENTION [0002] Dementia is a neurological disease that results in loss of mental capacity and is associated with widespread reduction in the number of nerve cells and brain tissue shrinkage. Memory is the mental capacity most often affected by dementia. The memory loss may first manifest itself in simple absentmindedness, a tendency to forget or misplace things, or to repeat oneself in conversation. As the dementia progresses, the loss of memory broadens in scope until the patient can no longer remember basic social and survival skills and function independently. Dementia can also result in a decline in the patient's language skills, spatial or temporal orientation, judgment, or other cognitive capacities. Dementia tends to run an insidious and progressive course. [0003] Alzheimer's disease (AD) is a degenerative brain disorder presented clinically by progressive loss of memory, cognition, reasoning, judgment, and emotional stability that gradually leads to profound mental deterioration and ultimately death. Individuals with AD exhibit characteristic beta amyloid deposits in the brain (beta amyloid plaques) and in cerebral blood vessels (beta amyloid angiopathy) as well as neurofibrillary tangles. On autopsy of AD patients, large numbers of these lesions, which are believed to be a causative precursor or factor in the development of disease, are generally found in areas of the human brain important for memory and cognitive function. Smaller numbers are found in the brains of most aged humans not showing clinical symptoms of AD. Beta amyloid plaques and beta amyloid angiopathy also characterize the brains of individuals with Down's syndrome (Trisomy 21) and Hereditary Cerebral Hemorrhage with Beta amyloidosis of the Dutch-Type, and other such disorders. [0004] Vascular Dementia (VaD) is defined as the loss of cognitive function resulting from ischemic, ischemic-hypoxic, or hemorrhagic brain lesions as a result of cardiovascular diseases and cardiovascular pathologic changes. VaD is a chronic disorder and the symptoms of VaD include cognitive loss, headaches, insomnia and memory loss. VaD may be caused by multiple strokes (MID or post-stroke dementia) but also by single strategic strokes, multiple lacunes, and hypoperfusive lesions such as border zone infarcts and ischemic periventricular leukoencephalopathy (Binswanger's disease). [0005] Patients suffering from neurodegenerative diseases, brain damage caused by stroke, dementia, Alzheimer's disease, or head injury often are afflicted with emotional problems associated with the disease or injury. The terms Involuntary Emotional Expression Disorder (IEED), emotional lability, and pseudobulbar affect are used by psychiatrists and neurologists to refer to a set of symptoms that are often observed in patients who have suffered a brain insult such as a head injury, stroke, brain tumor, or encephalitis, or who are suffering from a progressive neurodegenerative disease such as Amyotrophic Lateral Sclerosis (ALS, also called motor neuron disease or Lou Gehrig's disease), Parkinson's disease, Alzheimer's disease, or multiple sclerosis (MS). In the great majority of such cases, emotional lability occurs in patients who have bilateral damage (damage which affects both hemispheres of the brain) involving subcortical forebrain structures. [0006] IEED is distinct from clinical forms of reactive or endogenous depression, and is characterized by intermittent spasmodic outbursts of emotion, such as anger, or expressions of irritability or frustration at inappropriate times or in the absence of any particular provocation. The feelings that accompany emotional lability are often described in words such as "disconnectedness," since patients are fully aware that an outburst is not appropriate in a particular situation, but they do not have control over their emotional displays. IEED is also referred to by the terms emotionalism, emotional incontinence, emotional discontrol, excessive emotionalism, and pathological laughing and crying. [0007] Emotional lability or pseudobulbar affect becomes a clinical problem when the inability to control emotional outbursts interferes in a substantial way with the ability to engage in family, personal, or business affairs. For example, a businessman suffering from early-stage ALS or Parkinson's disease might become unable to sit through business meetings, or a patient might become unable to go out in public, such as to a restaurant or movie, due to transient but intense inability to keep from crying or laughing at inappropriate times in front of other people. These symptoms can occur even though the patient still has more than enough energy and stamina to do the physical tasks necessary to interact with other people. Such outbursts, along with the feelings of annoyance, inadequacy, and confusion that they usually generate and the visible effects they have on other people, can severely aggravate the other symptoms of the disease; they lead to feelings of ostracism, alienation, and isolation, and they can render it very difficult for friends and family members to provide tolerant and caring emotional support for the patient. [0008] People with diseases such as Alzheimer's also often have behavior problems in the late afternoon and evening. They may become demanding, suspicious, upset or disoriented, see or hear things that are not there and believe things that aren't true. Or they may pace or wander around the house when others are sleeping. While experts are unsure how or why this behavior occurs, they suspect that the problem of late afternoon confusion, which is sometimes called "sundowning," or "sundown syndrome," may be due to these factors: the person with Alzheimer's can't see well in dim light and becomes confused; the impaired person may have a hormone imbalance or a disturbance in his/her "biological clock"; the person with Alzheimer's gets tired at the end of the day and is less able to cope with stress; the person is involved in activities all day long and grows restless if there's nothing to do in the late afternoon or evening; the caregiver communicates fatigue and stress to the person with Alzheimer's and the person becomes anxious. [0009] Recent estimates indicate that more than 19 million Americans over the age of 18 years experience a depressive illness each year. The American Psychiatric Association recognizes several types of clinical depression, including Mild Depression (Dysthymia), Major Depression, and Bipolar Disorder (Manic-Depression). Depression is defined by a constellation of chronic symptoms that include sleep problems, appetite problems, anhedonia or lack of energy, feelings of worthlessness or hopelessness, difficulty concentrating, suicidal thoughts, mood swings (feelings of sadness, abandonment,
Load more

Recommended publications
  • Create a Healing Environment for Patients with Pseudobulbar Affect by Maude Mcgill, Phd, RN-BC, and Marzell Mcgill, BA, LPN
    Strictly Clinical Create a healing environment for patients with pseudobulbar affect By Maude McGill, PhD, RN-BC, and Marzell McGill, BA, LPN tact their provider for prompt appropriate treatment. • Signs and symptoms include: Teach patients how to manage PBA • emotional responses (such as crying or laughing) for optimal quality of life. that don’t fit the situation • emotional episodes lasting longer than expected • sudden emotional outbursts (these outbursts can I just don’t understand why Mom is crying. When I include frustration, anger, laughter, or crying) walked in the room, she was happy and calm. Then, • moments of intense emotions that are out of the when I asked her about her day, her smile turned into patient’s control a frown and she started crying uncontrollably. I’ve nev - • facial expressions that don’t match the emotional er seen her cry like that. I’m concerned. response. EMOTIONS ARE NATURAL . We’ve all heard the cliché, “Emotions make us human.” People cry when they’re hurt and laugh when things are funny. However, mil - lions of people find that controlling their emotions is hard because of pseudobul - bar affect (PBA). PBA refers to inappropriate, involun - tary, or uncontrollable laughing or crying caused by the residual effects of a nervous system disorder. Al - though PBA is closely asso - ciated with post-stroke pa - tients, it can occur with any nervous system condition, including Alzheimer’s dis - ease, traumatic brain injury, and multiple sclerosis. Sci - entists have labeled PBA a disorder of emotional incon - tinence (patients can’t control their emotional respons - Navigating the new normal of PBA es).
    [Show full text]
  • IHH Notification Form Guide
    Integrated Health Home Health Home Notification Form Guide Introduction This is to assist in providing the Health Home with information on criteria and how to enroll the member into an Integrated Health Home (IHH). Enrollment Criteria Member needs to 1. Be eligible for Medicaid. 2. Have 1 or more Serious Mental Illness (SMI) or Serious Emotional Disturbance (SED). 3. Meet the Functional Impairment (FI) as determined by a Licensed Mental Health Professional. SMI & SED Definitions Diagnosis must be determined by use the Diagnostic and Statistical Manual (DSM) of Mental Disorders published by the American Psychiatric Association or its most recent International Classification of Diseases (ICD). SMI is defined as an Adult that has a persistent or chronic mental illness, a behavioral, or emotional disorder that causes serious functional impairment and substantially interferes with or limits one or more major life activities including functioning in the family, school, employment or community. SMI may co-occur with substance use disorder, developmental, neurodevelopmental or intellectual disabilities but those diagnoses may not be the clinical focus for health home services. SED is defined by a Child having a diagnosable mental, behavioral or emotional disorder which results in a functional impairment that substantially interferes with or limits the child’s role or functioning in family, school, or community activities. SED may co-occur with substance use disorder, developmental, neurodevelopmental or intellectual disabilities but those diagnoses may not be the clinical focus for health home services. Mental Health Professional Definition Mental health professional meets all of the following conditions: 1. Holds at least a master’s degree in a mental health field including, but not limited to, psychology, counseling and guidance, psychiatric nursing and social work; or is a doctor of medicine or osteopathic medicine; and 2.
    [Show full text]
  • Nuedexta, INN-Dextromethorphan/Quinidine
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT NUEDEXTA 15 mg/9 mg hard capsules 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each capsule contains dextromethorphan hydrobromide monohydrate, equivalent to 15.41 mg dextromethorphan and quinidine sulfate dihydrate, equivalent to 8.69 mg quinidine. Excipient with known effect: Each hard capsule contains 119.1 mg of lactose (as monohydrate). For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Hard capsule Brick red gelatin capsule, size 1, with “DMQ / 20-10” printed in white ink on the capsule. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications NUEDEXTA is indicated for the symptomatic treatment of pseudobulbar affect (PBA) in adults (see section 4.4). Efficacy has only been studied in patients with underlying Amyotrophic Lateral Sclerosis or Multiple Sclerosis (see section 5.1). 4.2 Posology and method of administration Posology The recommended starting dose is NUEDEXTA 15 mg/9 mg once daily. The recommended dose titration schedule is outlined below: Week 1 (day 1-7): The patient should take one NUEDEXTA 15 mg/9 mg capsule once daily, in the morning, for the initial 7 days. Weeks 2-4 (day 8-28): The patient should take one NUEDEXTA 15 mg/9 mg capsule, two times per day, one in the morning and one in the evening, 12-hours apart, for 21 days. From Week 4 on: If the clinical response with NUEDEXTA 15 mg/9 mg is adequate, the dose taken in weeks 2-4 should be continued. 2 If the clinical response with NUEDEXTA 15 mg/9 mg is inadequate, NUEDEXTA 23 mg/9 mg should be prescribed, taken two times per day, one in the morning and one in the evening, 12 hours apart.
    [Show full text]
  • What's New in Psychopharmacology
    Wednesday, 3:00 – 4:30, F2 What's New in Psychopharmacology Joel M. Sanchez, MD [email protected] Objectives: Identify advances in clinical assessment and management of selected healthcare issues related to persons with developmental disabilities Notes: 4/7/2016 What’s New in Nuedexta Psychopharmacology • A new medication for pseudobulbar affect (PBA) • Pseudobulbar Affect: Joel M. Sanchez, M.D. • Frequent, uncontrollable outbursts of crying or laughing in people with certain neurologic conditions or brain injuries Diplomate of the American Board of Psychiatry and Neurology, Psychiatry • Episodes may occur several times per day and can last seconds to minutes Diplomate of the American Board of Psychiatry and Neurology, Child/Adolescent Psychiatry • “emotional incontinence” • “pathological laughing and crying” The Right Door for Hope, Recovery and Wellness Wedgwood Christian Services Turning Leaf Behavioral Health Services Community Mental Health Authority - CEI ADHD Medications Antidepressants • Stimulants • SSRIs • Adzenys XR-ODT (amphetamine extended release oral dissolving tablet) • Brintellix (vortioxetine) • Quillivant XR (methylphenidate extended release liquid) • Viibryd (vilazodone) • Daytrana (methylphenidate transdermal) • SNRIs • Non-Stimulants • Fetzima (levomilnacipran) • Clonidine (Catapres / Kapvay) • Pristiq (desvenlafaxine) • Guanfacine (Tenex / Intuniv) • Strattera (atomoxetine) Antipsychotics Blood Pressure Medications • Abilify Maintena & Aristada (aripiprazole) • What’s Old is New • Every 4 weeks or Every 4-6
    [Show full text]
  • Pathological Laughter and Crying in Patients with Multiple System Atrophy-Cerebellar Type
    Movement Disorders Vol. 22, No. 6, 2007, pp. 798–803 © 2007 Movement Disorder Society Pathological Laughter and Crying in Patients with Multiple System Atrophy-Cerebellar Type Josef Parvizi, MD, PhD,1* Jeffrey Joseph, MD, PhD,1 Daniel Z. Press, MD,1 and Jeremy D. Schmahmann, MD2 1Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA 2Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA Abstract: In the cerebellar type of multiple system atrophy or crying, or both in 9 more patients. Our finding of about (MSA-C), the burden of pathological changes involves the 36% occurrence suggests that the problem of dysregulation cerebellum and its associated brainstem structures in the of emotional expression is more prevalent in MSA-C basis pontis and the inferior olivary nucleus, and as a result, than the paucity of reports in the literature suggests. Our the clinical phenotype is dominated early on by the cerebel- findings are consistent with the view that the cerebellum and lar dysfunction. We report our clinical and post mor- its interconnected structures may be involved in the regula- tem findings in a patient with MSA-C who exhibited patho- tion of emotional expression. © 2007 Movement Disorder logical laughter in the absence of any congruent changes of Society mood. A review of the clinical notes of 27 other patients Key words: olivopontocerebellar atrophy; disinhibition; with MSA-C revealed a problem with pathological laughter, emotion; behavior; pseudobulbar affect Pathological laughter and crying (PLC) is a condition Numerous terms have been introduced to describe the in which a patient with an underlying neurological dis- problem of inappropriate or exaggerated laughing and order exhibits episodes of laughter or crying or both, crying.
    [Show full text]
  • Nuedexta, INN-Dextromethorphan/Quinidine
    authorised longer no product Medicinal SUMMARY OF PRODUCT CHARACTERISTICS ANNEX I 1 1. NAME OF THE MEDICINAL PRODUCT NUEDEXTA 15 mg/9 mg hard capsules 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each capsule contains dextromethorphan hydrobromide monohydrate, equivalent to 15.41 mg dextromethorphan and quinidine sulfate dihydrate, equivalent to 8.69 mg quinidine. Excipient with known effect: Each hard capsule contains 119.1 mg of lactose (as monohydrate). For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Hard capsule Brick red gelatin capsule, size 1, with “DMQ / 20-10” printed in white inkauthorised on the capsule. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications longer NUEDEXTA is indicated for the symptomatic treatmentno of pseudobulbar affect (PBA) in adults (see section 4.4). Efficacy has only been studied in patients with underlying Amyotrophic Lateral Sclerosis or Multiple Sclerosis (see section 5.1). 4.2 Posology and method of administration product Posology The recommended starting dose is NUEDEXTA 15 mg/9 mg once daily. The recommended dose titration schedule is outlined below: Week 1 (day 1-7): The patientMedicinal should take one NUEDEXTA 15 mg/9 mg capsule once daily, in the morning, for the initial 7 days. Weeks 2-4 (day 8-28): The patient should take one NUEDEXTA 15 mg/9 mg capsule, two times per day, one in the morning and one in the evening, 12-hours apart, for 21 days. From Week 4 on: If the clinical response with NUEDEXTA 15 mg/9 mg is adequate, the dose taken in weeks 2-4 should be continued.
    [Show full text]
  • Clinical Guidelines/Recommendations
    Volume 1, Issue Number 12; July 8, 2005 News Highlights from June 20 – July 1, 2005 Coming in August … TrendsRx® Drug Pipeline and News will be getting a new look! Look for the same up-to-date information with a fresh new format! PIPELINE Generic Medicines for the Treatment of HIV Tentatively Approved Under the Government’s Emergency Plan for AIDS Relief On June 20, 2005, the United States Food and Drug Administration (FDA) announced tentative approval of two applications for nevirapine tablets, manufactured by Ranbaxy Laboratories Limited (Guragon, India) and Aurobindo Pharma Limited (Hyderabad, India).1 These products will be the first generic versions of Viramune® tablets, manufactured by Boehringer Ingelheim. Generic nevirapine will be available for purchase under the President’s Emergency Plan for AIDS Relief (PEPFAR).1 This plan allows for the availability of safe and effective AIDS treatments quicker and at a lower cost as part of worldwide HIV/AIDS relief.1-3 It is designed to prevent new HIV infections, treat HIV-infected people, and care for HIV-affected individuals.1-3 Tentative approval under PEPFAR means that although existing patents and/or exclusivity prevent marketing of these products in the United States, they meet the FDA standards for quality, safety and efficacy.1-3 On June 24 and July 1, 2005, respectively, the FDA also announced tentative approval of efavirenz tablets and stavudine capsules manufactured by Aurbindo Pharma LTD. (Hyderabad, India).2 These are the first generic versions of Sustiva® and Zerit®, respectively, manufactured by Bristol-Myers Squibb. Both generic products will also be considered for purchase under the PEPFAR.2 Nevirapine and efavirenz are non-nucleoside reverse transcriptase inhibitors (NNRTIs) used in combination with other medicines for the treatment of HIV-1 infection.1-2 Stavudine is a nucleoside reverse transcriptase inhibitor (NRTI) also used in combination with other medicines for the treatment of HIV-1 infection.3 © Copyright 2005 Caremark.
    [Show full text]
  • Pseudobulbar Affect: When Patients Laugh Or Cry, but Don’T Know Why
    Pseudobulbar affect: When patients laugh or cry, but don’t know why Disruption of neural circuitry undermines voluntary control of affect seudobulbar affect (PBA) is a disorder of affective expression that manifests as stereotyped and frequent Poutbursts of crying (not limited to lacrimation) or laugh- ter. Symptoms are involuntary, uncontrolled, and exaggerated or incongruent with current mood. Episodes, lasting a few seconds to several minutes, may be unprovoked or occur in response to a mild stimulus, and patients typically display a normal affect between episodes.1 PBA is estimated to affect 1 to 2 million people in the United States, although some studies suggest as many as 7 million,1,2 depending on the evaluation method and threshold criteria used.3 Many terms have been used to describe aspects of PBA (Table 14 and Box, page 585-10). This abundance of often con- flicting terminology is thought to have impeded efforts to © SIMONE GOLOB/CORBIS categorize emotional expression disorders, determine their Benjamin Frock, MD prevalence, and evaluate clinical evidence of potential ther- PGY-1 Resident apeutic options.11 Vanderbilt University School of Medicine Nashville, Tennessee Andrew Williams, MD Where to look for pseudobulbar affect PGY-1 Resident Oregon Health & Science University PBA has been most commonly described in 6 major neuro- Portland, Oregon logic disorders: Jason P. Caplan, MD • Alzheimer’s disease Professor and Chair of Psychiatry • amyotrophic lateral sclerosis (ALS) Creighton University School of Medicine • multiple sclerosis (MS) Phoenix Regional Campus Phoenix, Arizona • Parkinson’s disease • stroke • traumatic brain injury (TBI). Disclosures Dr. Caplan has served as a consultant to Avanir Pharmaceuticals, an independent subsidiary of Otsuka America, Inc., manufacturer of the formulation of dextromethorphan/quinidine discussed Current Psychiatry in this article.
    [Show full text]
  • Your Guide to Understanding PBA
    I cry (or sometimes “laugh) out of nowhere, all the time. I can’t seem to control it, and it’s not the way I feel.” Your Guide to Understanding PBA If this sounds like you, and you have a neurologic condition or brain injury, you might have PseudoBulbar Affect (PBA). Learning about PBA is your first step in discovering how to manage the condition. Take a look through this guide to find out more about PBA and what to ask your doctor. Learn more about PBA You’ve taken a great first step in finding out more about PBA This kit is full of information to help you learn about the symptoms of PBA, assess your own symptoms more closely, and have a productive and honest discussion with your doctor. Be sure to fill out your information, and then print or email it to yourself so you can show it to your doctor. Contents of the kit: Your Guide to Understanding PseudoBulbar Affect (PBA) • What does PBA feel like? • What exactly is PBA? • Sometimes PBA can be mistaken for other conditions • What’s the difference between PBA and Depression? • Living with the symptoms of PBA • Reminders for my next doctor’s appointment Your short PBA quiz • Instructions • Take the quiz—print and take to your doctor Preparing for Your Doctor’s Visit • Tips for your visit • Track your episodes • Describe your episodes • 5 questions for you and your doctor What does PBA feel like? These are real quotes from people who have PBA, and they’re not alone. While there are almost 2 million people in the US with neurologic conditions or traumatic brain injury who have PBA, over 7 million people in the US have symptoms that suggest PBA.* PBA episodes can be confusing, frustrating, and draw unwanted attention.
    [Show full text]
  • Pseudobulbar Affect
    Pseudobulbar Affect Identifying Pseudobulbar Affect in Alzheimer’s Disease and Dementia David W Crumpacker, MD1 and William A Engelman, MD2 1. Psychiatrist and Neurologist, Private Practice, Plano, Texas, US; 2. Clinical Scientist and Senior Research Associate, Evidera, Lexington, Massachusetts, US Abstract Pseudobulbar affect (PBA) can be challenging to differentiate from the symptoms of various neurological diseases with which it is associated. In patients with Alzheimer’s disease (AD) and dementia such a diagnosis can be particularly difficult as illustrated by a case of an elderly male with sudden tearful outbursts, which is reported and discussed here. PBA attacks are often incorrectly attributed to emotion or distress in response to memory loss or a result of depression or dementia. PBA is common, affecting between 10–40 % of people with AD but is frequently not detected or is misdiagnosed. Multiple authors have published clinical criteria for identifying PBA; in sum, it is described as a condition affecting the brain with episodes of laughing or crying that are sudden and unpredictable, occur without warning and are excessive, exaggerated, or not appropriate to the stimuli and are involuntary and difficult to control. Differentiating PBA from depression and other behavioral disturbances in AD and dementia is helpful to patients by identifying a specific cause of their symptoms and enabling appropriate management. Various different approaches have been taken in the treatment of PBA. A combination of dextromethorphan and quinidine has been shown in well-controlled trials and in clinical use to control the symptoms of PBA associated with several neurological diseases including AD and to reduce the burden on patients and their caregivers.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,973,049 B2 Tung (45) Date of Patent: Jul
    US007973 049B2 (12) United States Patent (10) Patent No.: US 7,973,049 B2 Tung (45) Date of Patent: Jul. 5, 2011 (54) MORPHINAN COMPOUNDS 2005/0129783 A1 6/2005 McCleary et al. 2005/0203125 A1 9, 2005 Yakatan et al. 2006, OO795O2 A1 4/2006 Lang (75) Inventor: Roger Tung, Lexington, MA (US) 2006/0094744 A1 5/2006 Maryanoff et al. 2007/0O82929 A1 4/2007 Gant et al. (73) Assignee: Concert Pharmaceuticals Inc., 2007,0191411 A1 8, 2007 Smith Lexington, MA (US) 2007/O197695 A1 8/2007 Potyen et al. 2008. O103122 A1 5, 2008 Veltri (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 FOREIGN PATENT DOCUMENTS WO WO95/26325 10, 1995 U.S.C. 154(b) by 712 days. WO WO 2007.118651 10/2007 (21) Appl. No.: 12/112,936 OTHER PUBLICATIONS (22) Filed: Apr. 30, 2008 Authorized officer Lee W. Young, International Search Report/Writ ten Opinion in PCT/US 10/27990 mailed Mar. 19, 2010, 11 pages. (65) Prior Publication Data “Combination of dextromethorphan and quinidine Sulphate” online). Prous Science Integrity, retrieved on Apr. 23, 2007). US 2008/O280936A1 Nov. 13, 2008 Retrieved from the Internet: <URL: http://integrity prous.com/integ rity servlet/xmlx.sl/pk prodlist.xml . D. Related U.S. Application Data Anastasia et al., “Simple and selective one-pot replacement of the N-methyl group of tertiary amines by quaternization and demethyla (60) Provisional application No. 60/915,130, filed on May tion with sodium sulfide or potassium thioacetate: an application to 1, 2007, provisional application No.
    [Show full text]
  • Calming Emotional Outbursts from Pseudobulbar AEct
    DECEMBER 2014/JANUARY 2015 BY DEBRA GORDON, MS Calming Emotional Outbursts from Pseudobulbar Aoect Research points to an eoective treatment for pseudobulbar aoect (PBA), a disorder that accompanies a number of dioerent neurological conditions. It's no laughing matter. A growing number of people with neurological disorders are complaining of embarrassing guttural laughs or too many unexplained tears, emotions that surface with no apparent rhyme or reason. While they may be perplexed, their doctors aren't. They attribute the emotional outbursts to a condition called pseudobulbar affect (PBA) that leaves people uncontrollably and inappropriately laughing or crying. Laughing and crying. iSTOCKPHOTO/RYANJLANE; iSTOCKPHOTO/DIANE39 PBA has been observed in patients with amyotrophic lateral sclerosis (ALS), Parkinson's disease, multiple sclerosis (MS), Alzheimer's disease, stroke, and traumatic brain injury (TBI). These patients often describe their loss of emotional control, including expressing inappropriate anger and frustration, as more debilitating than the underlying disease. "It's very disabling and embarrassing," says Andrew Tarulli, MD, an assistant professor of neurology at Harvard Medical School who is also a member of the American Academy of Neurology (AAN). "The very interesting thing to me about PBA is that patients are expressing emotion we can observe but they are not feeling it to the extent that it would seem they should," says Mary Kay Floeter, MD, PhD, a senior clinician with the Human Spinal Physiology Unit of the National Institute of Musculoskeletal Disorders and Stroke, which is part of the National Institutes of Health. Nonetheless, she says, her studies find that there is always a specific trigger for the outburst, such as seeing something on TV that is sad.
    [Show full text]