Clozapine for Treating Schizophrenia
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Modern Antipsychotic Drugs: a Critical Overview
Review Synthèse Modern antipsychotic drugs: a critical overview David M. Gardner, Ross J. Baldessarini, Paul Waraich Abstract mine was based primarily on the finding that dopamine ago- nists produced or worsened psychosis and that antagonists CONVENTIONAL ANTIPSYCHOTIC DRUGS, used for a half century to treat were clinically effective against psychotic and manic symp- a range of major psychiatric disorders, are being replaced in clini- 5 toms. Blocking dopamine D2 receptors may be a critical or cal practice by modern “atypical” antipsychotics, including ari- even sufficient neuropharmacologic action of most clinically piprazole, clozapine, olanzapine, quetiapine, risperidone and effective antipsychotic drugs, especially against hallucina- ziprasidone among others. As a class, the newer drugs have been promoted as being broadly clinically superior, but the evidence for tions and delusions, but it is not necessarily the only mecha- this is problematic. In this brief critical overview, we consider the nism for antipsychotic activity. Moreover, this activity, and pharmacology, therapeutic effectiveness, tolerability, adverse ef- subsequent pharmacocentric and circular speculations about fects and costs of individual modern agents versus older antipsy- altered dopaminergic function, have not led to a better un- chotic drugs. Because of typically minor differences between derstanding of the pathophysiology or causes of the several agents in clinical effectiveness and tolerability, and because of still idiopathic psychotic disorders, nor have they provided a growing concerns about potential adverse long-term health conse- non-empirical, theoretical basis for the design or discovery quences of some modern agents, it is reasonable to consider both of improved treatments for psychotic disorders. older and newer drugs for clinical use, and it is important to inform The neuropharmacodynamics of specific modern anti- patients of relative benefits, risks and costs of specific choices. -
Schizophrenia Care Guide
August 2015 CCHCS/DHCS Care Guide: Schizophrenia SUMMARY DECISION SUPPORT PATIENT EDUCATION/SELF MANAGEMENT GOALS ALERTS Minimize frequency and severity of psychotic episodes Suicidal ideation or gestures Encourage medication adherence Abnormal movements Manage medication side effects Delusions Monitor as clinically appropriate Neuroleptic Malignant Syndrome Danger to self or others DIAGNOSTIC CRITERIA/EVALUATION (PER DSM V) 1. Rule out delirium or other medical illnesses mimicking schizophrenia (see page 5), medications or drugs of abuse causing psychosis (see page 6), other mental illness causes of psychosis, e.g., Bipolar Mania or Depression, Major Depression, PTSD, borderline personality disorder (see page 4). Ideas in patients (even odd ideas) that we disagree with can be learned and are therefore not necessarily signs of schizophrenia. Schizophrenia is a world-wide phenomenon that can occur in cultures with widely differing ideas. 2. Diagnosis is made based on the following: (Criteria A and B must be met) A. Two of the following symptoms/signs must be present over much of at least one month (unless treated), with a significant impact on social or occupational functioning, over at least a 6-month period of time: Delusions, Hallucinations, Disorganized Speech, Negative symptoms (social withdrawal, poverty of thought, etc.), severely disorganized or catatonic behavior. B. At least one of the symptoms/signs should be Delusions, Hallucinations, or Disorganized Speech. TREATMENT OPTIONS MEDICATIONS Informed consent for psychotropic -
Current P SYCHIATRY
Current p SYCHIATRY N ew Investigators Tips to manage and prevent discontinuation syndromes Informed tapering can protect patients when you stop a medication Sriram Ramaswamy, MD Shruti Malik, MBBS, MHSA Vijay Dewan, MD Instructor, department of psychiatry Foreign medical graduate Assistant professor Creighton University Department of psychiatry Omaha, NE University of Nebraska Medical Center Omaha, NE bruptly stopping common psychotropics New insights on psychotropic A —particularly antidepressants, benzodi- drug safety and side effects azepines, or atypical antipsychotics—can trigger a discontinuation syndrome, with: This paper was among those entered in the 2005 • rebound or relapse of original symptoms Promising New Investigators competition sponsored • uncomfortable new physical and psycho- by the Neuroleptic Malignant Syndrome Information Service (NMSIS). The theme of this year’s competition logical symptoms was “New insights on psychotropic drug safety and • physiologic withdrawal at times. side effects.” To increase health professionals’ awareness of URRENT SYCHIATRY 1 C P is honored to publish this peer- the risk of these adverse effects, this article reviewed, evidence-based article on a clinically describes discontinuation syndromes associated important topic for practicing psychiatrists. with various psychotropics and offers strategies to NMSIS is dedicated to reducing morbidity and anticipate, recognize, and manage them. mortality of NMS by improving medical and psychiatric care of patients with heat-related disorders; providing -
Guidance on Strategies to Promote Best Practice in Antipsychotic Prescribing for Children and Adolescents
Acknowledgments This report was prepared for the Substance Abuse and Mental Health Services Administration (SAMHSA) under contract number HHSS2832017000751/HHSS28342001T with SAMHSA, U.S. Department of Health and Human Services (HHS), in consultation with Thomas I. Mackie, Ph.D., M.P.H. Nadine Benton served as contracting officer representative with Stacey Lee as the task lead. Disclaimer The views, opinions, and content of this publication are those of the author and do not necessarily reflect the views, opinions, or policies of SAMHSA or HHS. Nothing in this document constitutes a direct or indirect endorsement by SAMHSA or HHS of any non‐Federal entity’s products, services, or policies, and any reference to non‐Federal entity’s products, services, or policies should not be construed as such. Public Domain Notice All material appearing in this publication is in the public domain and may be reproduced or copied without permission from SAMHSA. Citation of the source is appreciated. However, this publication may not be reproduced or distributed for a fee without the specific, written authorization of the Office of Communications, SAMHSA, HHS. Electronic Access This publication may be downloaded from http://store.samhsa.gov. Recommended Citation Substance Abuse and Mental Health Services Administration: Guidance on Strategies to Promote Best Practice in Antipsychotic Prescribing for Children and Adolescents. HHS Publication No. PEP19‐ ANTIPSYCHOTIC‐BP. Rockville, MD: Office of Chief Medical Officer. Substance Abuse and Mental Health Services Administration, 2019. Originating Office Office of Behavioral Health Equity and Office of Chief Medical Officer, Substance Abuse and Mental Health Services Administration, 5600 Fishers Lane, Rockville, MD 20857, HHS Publication No. -
Another View of the History of Antipsychotic Drug Discovery and Development
Molecular Psychiatry (2012) 17, 1168–1173 & 2012 Macmillan Publishers Limited All rights reserved 1359-4184/12 www.nature.com/mp PERSPECTIVE Another view of the history of antipsychotic drug discovery and development WT Carpenter Jr1 and JM Davis2 Chlorpromazine initiated effective pharmacotherapy for schizophrenia 60 years ago. This discovery initiated or stimulated key developments in the field of psychiatry. Nonetheless, advances in pharmacotherapy of schizophrenia have been modest. Psychosis remains the primary aspect of psychopathology addressed, and core pathologies such as cognition and negative symptom remain unmet therapeutic challenges. New clinical and basic neuroscience paradigms may guide the near future and provide a more heuristic construct for novel and innovative discovery. Molecular Psychiatry (2012) 17, 1168–1173; doi:10.1038/mp.2012.121; published online 14 August 2012 Keywords: antipsychotic drugs; chlorpromazine; history; psychopharmacology; schizophrenia Efficacious therapy for persons suffering with schizophrenia and hindered the development of practical case management and related psychotic disorders was not established before the dis- supportive therapies, and created a flawed psychotherapy versus covery of the antipsychotic properties of chlorpromazine reported medication polemic. Society was sometimes viewed as causative in 1952.1 Following the remarkable success in treating and pre- of schizophrenia leading to legal efforts to impede treatment. The venting tertiary syphilis with antibiotic therapy, there was -
Antipsychotic Combinations
Graylands Hospital DRUG BULLETIN Pharmacy Department Brockway Road Mount Claremont WA 6010 Telephone (08) 9347 6400 Email [email protected] Fax (08) 9384 4586 Antipsychotic Combinations Graylands Hospital Drug Bulletin 2008 Vol. 15 No. 3 February ISSN 1323-1251 Antipsychotic combinations Reasons for antipsychotic combinations Despite the development of efficacious medications for the treatment of schizophrenia, many people do There are a number of theoretical benefits and not respond adequately. To address this problem, reasons cited for antipsychotic combination the use of two or more antipsychotics simultaneously prescribing, these include: is a commonly employed treatment strategy. Although the use of combination antipsychotics is Complementary mechanisms of action4 (e.g. common in clinical practice, the risks and benefits adding an antipsychotic with strong dopamine have not been systematically evaluated to date. As a D2 blockade to a weak D2 blocker) result, current Australian treatment algorithms Partial replacement of antipsychotic action for including the Royal Australian and New Zealand drugs with intolerable adverse effects at higher College of Psychiatry Schizophrenia Guidelines and 5 doses (e.g. adding quetiapine to clozapine to the Western Australian Therapeutic Advisory Group minimise metabolic adverse effects) Antipsychotic Guidelines advise against the use of combined antipsychotics, except for short periods of Alternative where clozapine cannot be used6 changeover1,2. Most data on antipsychotic -
Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice
pharmaceuticals Article Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice Geng-Ruei Chang 1,* , Po-Hsun Hou 2,3, Wei-Cheng Yang 4, Chao-Min Wang 1 , Pei-Shan Fan 1, Huei-Jyuan Liao 1 and To-Pang Chen 5,* 1 Department of Veterinary Medicine, National Chiayi University, 580 Xinmin Road, Chiayi 60054, Taiwan; [email protected] (C.-M.W.); [email protected] (P.-S.F.); [email protected] (H.-J.L.) 2 Department of Psychiatry, Taichung Veterans General Hospital, 1650 Taiwan Boulevard (Section 4), Taichung 40705, Taiwan; [email protected] 3 Faculty of Medicine, National Yang-Ming University, 155 Linong Street (Section 2), Taipei 11221, Taiwan 4 School of Veterinary Medicine, National Taiwan University, 1 Roosevelt Road (Section 4), Taipei 10617, Taiwan; [email protected] 5 Division of Endocrinology and Metabolism, Show Chwan Memorial Hospital, 542 Chung-Shan Road (Section 1), Changhua 50008, Taiwan * Correspondence: [email protected] (G.-R.C.); [email protected] (T.-P.C.); Tel.: +886-5-2732946 (G.-R.C.); +886-4-7256166 (T.-P.C.) Abstract: Doxepin is commonly prescribed for depression and anxiety treatment. Doxepin-related disruptions to metabolism and renal/hepatic adverse effects remain unclear; thus, the underlying mechanism of action warrants further research. Here, we investigated how doxepin affects lipid Citation: Chang, G.-R.; Hou, P.-H.; change, glucose homeostasis, chromium (Cr) distribution, renal impairment, liver damage, and fatty Yang, W.-C.; Wang, C.-M.; Fan, P.-S.; liver scores in C57BL6/J mice subjected to a high-fat diet and 5 mg/kg/day doxepin treatment for Liao, H.-J.; Chen, T.-P. -
Treatment Options for Clozapine-Induced Enuresis: a Review of Clinical Effectiveness
TITLE: Treatment Options for Clozapine-Induced Enuresis: A Review of Clinical Effectiveness DATE: 27 September 2010 CONTEXT AND POLICY ISSUES: Clozapine is an atypical antipsychotic indicated in the management of treatment-resistant schizophrenia.1 Clozapine binds dopamine receptors as well as exerting potent anticholinergic, adrenolytic, antihistaminic, and antiserotoninergic activity.1 It has been shown to be efficacious in treating both the positive (e.g., hallucinations) and negative symptoms (e.g., social withdrawal) associated with schizophrenia. Patients treated with clozapine may experience adverse effects ranging in severity from relatively benign to serious and potentially life-threatening conditions such as seizures and agranulocytosis.1,2 One potential adverse effect is enuresis, or an inability to control urination, which can cause emotional stress and poor compliance among the affected patients.3 The true prevalence of clozapine-induced enuresis has yet to be determined as published estimates range from 0.23% to 44%.4,5 The reasons for this lack of consistency is are unclear and may be related to differences in dosage,6 ethnicity,7 and treatment setting.3 The mechanism for clozapine-induced enuresis has not been fully elucidated; however, a leading hypothesis involves blockade of the α-adrenergic receptors resulting in a decrease in internal bladder sphincter tone.7 A number of treatments are available for the management of enuresis including desmopressin,8 tricyclic antidepressants,9 anticholinergics,10 and alarms.11 However, there is currently no universally accepted approach to addressing clozapine-induced enuresis.2,6 This report reviews the safety and effectiveness of the various treatment strategies for clozapine- induced enuresis. -
Clozapine and Gastrointestinal Adverse Effects – a Pain in the Gut? Graylands Hospital Drug Bulletin 2004 Vol
Clozapine and Gastrointestinal Adverse Effects – A Pain in the Gut? Graylands Hospital Drug Bulletin 2004 Vol. 12 No. 3 September ISSN 1323-1251 Gastrointestinal adverse effects of clozapine impaction5. The patient died three weeks after are very common and include nausea, presentation from refractory shock and vomiting and constipation. Other troublesome progressive multi-system organ failure, unwanted effects include dry mouth and despite maximal care. hypersalivation, which involve the autonomic nervous system. A further case involved a 29 year old man who had only been taking clozapine for 36 Constipation is a particularly common days2. He died after aspiration of vomitus adverse effect that has been reported to occur secondary to bowel obstruction. in 14-60% of patients1,2. The management of clozapine-induced constipation has been the Intestinal Obstruction/Occlusion subject of a past Drug Bulletin3. Clozapine’s association with constipation could be There is a French report of three cases of intestinal occlusion in clozapine treated explained by its potent anticholinergic 6 properties. patients, one of which was fatal . Another report describes two cases of Rarely, clozapine-induced constipation has 7 lead to serious complications including ileus, clozapine-induced intestinal obstruction . bowel obstruction and necrotising colitis. A One of these involved a 51 year old man with review was conducted to determine what no past history of constipation, who had been serious gastrointestinal adverse effects have taking clozapine for two months. He suffered been reported in the literature and these are from an intestinal obstruction, from which he discussed below. fully recovered and clozapine was recommenced. The other case involved a 35 Faecal Impaction year old woman who had been taking clozapine for four months when she There are three reported cases of death developed abdominal symptoms. -
Activities of the Antipsychotic Drugs Haloperidol and Risperidone on Behavioural Effects Induced by Ketamine in Mice
Sci Pharm www.scipharm.at Research article Open Access Activities of the Antipsychotic Drugs Haloperidol and Risperidone on Behavioural Effects Induced by Ketamine in Mice 1 1 Marta de Oliveira Viana ARRUDA , Paula Matias SOARES , José Eduardo 1 1 Ribeiro HONÓRIO Jr. , Raquel Cristina de Sousa LIMA , Edna Maria 2 2 Camelo CHAVES , Rodrigo de Freitas Guimarães LOBATO , Ana Luíza de 2 2 Aguiar Rocha MARTIN , Gabriel Teixeira Montesuma SALES , 1 1 Krishnamurti de Moraes CARVALHO , Ana Maria Sampaio ASSREUY , 2 2 Eliane Magalhães de BRITO , Silvânia Maria Mendes VASCONCELOS * 1 Superior Institute of Biomedical Sciences, Academic Master in Physiological Sciences, State University of Ceará, Fortaleza, Ceará, Brazil. 2 Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil. * Corresponding author. E-mails: [email protected] or [email protected] (S. M. M. Vasconcelos) Sci Pharm. 2008; 76: 673–687 doi:10.3797/scipharm.0810-11 Published: November 28th 2008 Received: October 17th 2008 Accepted: November 27th 2008 This article is available from: http://dx.doi.org/10.3797/scipharm.0810-11 © Arruda et al; licensee Österreichische Apotheker-Verlagsgesellschaft m. b. H., Vienna, Austria. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract This study presents the actions of risperidone (Risp) and haloperidol (Hal) on the behavioral effects elicited by ketamine (Ket) on open-field (OF), rota rod (RR) and tail suspension (TS) tests in mice. -
HALDOL Brand of Haloperidol Injection
HALDOL® brand of haloperidol injection (For Immediate Release) WARNING Increased Mortality in Elderly Patients with Dementia-Related Psychosis: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10 week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. HALDOL Injection is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS). DESCRIPTION Haloperidol is the first of the butyrophenone series of major antipsychotics. The chemical designation is 4-[4-(p-chlorophenyl)-4-hydroxypiperidino] 4’-fluorobutyrophenone and it has the following structural formula: HALDOL (haloperidol) is available as a sterile parenteral form for intramuscular injection. The injection provides 5 mg haloperidol (as the lactate) and lactic acid for pH adjustment between 3.0 – 3.6. -
Atypical Antipsychotics
Caring for Residents with Dementia: A Guide for Behavior Management and Evidence-Based Medication Use A Toolkit This project is funded by the Agency for Healthcare Research and Quality (AHRQ). This toolkit was created by researchers at the University of Massachusetts Medical School, in partnership with Qualidigm. Introduction This toolkit contains information, tools, and resources that can help you and others in your nursing home care for people with dementia. Patients with dementia are sometimes prescribed medications, called atypical antipsychotics. One important goal of this toolkit is to increase awareness of the issues surrounding the use of these medications for behavior management. The tabs mark sections specifically designed to meet the needs of the different people who work in nursing Too often we homes. underestimate the power of a touch, a For example, direct care staff will find the materials in smile, a kind word, a Section 3 helpful, as they include resources and tools for listening ear, an honest managing challenging behaviors. Many of the pages in compliment, or the this toolkit are intended to be copied and shared with smallest act of caring, others in your nursing home. all of which have the potential to turn a life There is no tool to help with one of the most important around. Leo Buscaglia things to remember when caring for your residents with ~ dementia: the ability to “walk a mile in the shoes” of these residents. Imagine how it would feel to have difficulty remembering things or to be unable to think clearly. How would you behave if you could not communicate your needs or problems with others? What if you could no longer take care of yourself and were dependent on strangers to feed, bathe, and help you in the bathroom? How would you like to be treated? There are a number of links to additional tools and materials included in this toolkit.