Antipsychotics
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Clinical Experience in Schizophrenia: a Neuromedicine New Option to Address Unmet Needs
Bhat L, Cantillon M, Ings R. Brilaroxazine (RP5063) Clinical Experience in Schizophrenia: A Neuromedicine New Option to Address Unmet Needs. J Neurol Neuromedicine (2018) 3(5): 39-50 www.jneurology.com www.jneurology.com Journal of Neurology && NeuromedicineNeuromedicine Review Article Open Access Brilaroxazine (RP5063) Clinical Experience in Schizophrenia: A New Option to Address Unmet Needs Laxminarayan Bhat*, Marc Cantillon, and Robert Ings Reviva Pharmaceuticals, Inc., Sunnyvale, CA, USA Article Info ABSTRACT Article Notes Schizophrenia is a condition comprising of both treatment and comorbidity Received: September 18, 2018 factors that both complicate its management and present multiple unmet needs. Accepted: October 22, 2018 Brilaroxazine (RP5063), a dopamine (D)/serotonin (5-HT) modulator, possesses in vitro *Correspondence: a broad pharmacology profile against D2/3/4 and 5-HT1A/2A/2B/6/7 receptors, Dr. Laxminarayan Bhat, 1250 Oakmead Parkway, Suite 210, nicotinic acetylcholine (α4β2) receptors, and the serotonin transporter. In Phase 1 Sunnyvale, CA 94085, USA; Telephone No. +1 (408) 816 1454; and 2 clinical experience in healthy volunteers, patients with schizophrenia and Fax No. +1 (408) 904 6270; ORCID Number: 0000-0003-0503- schizoaffective disorder, brilaroxazine was well tolerated, with the repeated 100 mg 8537; Email: [email protected]. oral dose as the maximum tolerated dose. Investigators observed no cardiometabolic, cardiovascular, prolactin, or neurologic complications. Adherence in Phase 2 was © 2018 Bhat L. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License good with discontinuation rates generally less than placebo. In a Phase 2 evaluation of patients with acute exacerbations in schizophrenia and schizoaffective disorders, brilaroxazine met its primary endpoint of significance versus placebo for Total Positive and Negative Symptom Scale (PANSS) Score at Day 28 as compared to baseline. -
2D6 Substrates 2D6 Inhibitors 2D6 Inducers
Physician Guidelines: Drugs Metabolized by Cytochrome P450’s 1 2D6 Substrates Acetaminophen Captopril Dextroamphetamine Fluphenazine Methoxyphenamine Paroxetine Tacrine Ajmaline Carteolol Dextromethorphan Fluvoxamine Metoclopramide Perhexiline Tamoxifen Alprenolol Carvedilol Diazinon Galantamine Metoprolol Perphenazine Tamsulosin Amiflamine Cevimeline Dihydrocodeine Guanoxan Mexiletine Phenacetin Thioridazine Amitriptyline Chloropromazine Diltiazem Haloperidol Mianserin Phenformin Timolol Amphetamine Chlorpheniramine Diprafenone Hydrocodone Minaprine Procainamide Tolterodine Amprenavir Chlorpyrifos Dolasetron Ibogaine Mirtazapine Promethazine Tradodone Aprindine Cinnarizine Donepezil Iloperidone Nefazodone Propafenone Tramadol Aripiprazole Citalopram Doxepin Imipramine Nifedipine Propranolol Trimipramine Atomoxetine Clomipramine Encainide Indoramin Nisoldipine Quanoxan Tropisetron Benztropine Clozapine Ethylmorphine Lidocaine Norcodeine Quetiapine Venlafaxine Bisoprolol Codeine Ezlopitant Loratidine Nortriptyline Ranitidine Verapamil Brofaramine Debrisoquine Flecainide Maprotline olanzapine Remoxipride Zotepine Bufuralol Delavirdine Flunarizine Mequitazine Ondansetron Risperidone Zuclopenthixol Bunitrolol Desipramine Fluoxetine Methadone Oxycodone Sertraline Butylamphetamine Dexfenfluramine Fluperlapine Methamphetamine Parathion Sparteine 2D6 Inhibitors Ajmaline Chlorpromazine Diphenhydramine Indinavir Mibefradil Pimozide Terfenadine Amiodarone Cimetidine Doxorubicin Lasoprazole Moclobemide Quinidine Thioridazine Amitriptyline Cisapride -
Chronic Olanzapine Or Sertindole Treatment Results in Reduced Oral Chewing Movements in Rats Compared to Haloperidol Xue-Min Gao, M.D., Kazuo Sakai, M.D., and Carol A
Chronic Olanzapine or Sertindole Treatment Results in Reduced Oral Chewing Movements in Rats Compared to Haloperidol Xue-Min Gao, M.D., Kazuo Sakai, M.D., and Carol A. Tamminga, M.D. Chronic haloperidol treatment typically produces late-onset, haloperidol-like chewing in rats, nor did movement ratings purposeless oral chewing movements in laboratory rats with after their chronic administration differ from placebo; a prevalence of 40 to 60%. Chronic clozapine does not whereas, haloperidol produced a 60% prevalence of produce these movements. Based on the phenomenologic purposeless chewing and a prevalence significantly and pharmacologic similarities between these rat chewing increased from placebo. This low rate of oral dyskinesias in movements and human tardive dyskinesia (TD), the animal rats is consistent with several of the preclinical movements are often used as a model of tardive dyskinesia characteristics of the drugs and correlates with their low (TD). Here we report results of the association of oral acute motor side effects in clinical trials. We propose, chewing movements in rats with chronic administration of although have not yet tested in humans, that these animal two new antipsychotic drugs, olanzapine and sertindole. results will predict low TD liability of these drugs. Because each of these antipsychotic drugs has a very low [Neuropsychopharmacology 19:428–433, 1998] incidence of acute Parkinsonism in human studies, they are © 1998 American College of Neuropsychopharmacology. candidates for showing a low tardive dyskinesia risk. Published by Elsevier Science Inc. Neither new drug produced a significant incidence of KEY WORDS: Dyskinesia; Olanzapine; Sertindole; movements parallel certain features (although not all) Haloperidol; Tardive dyskinesia; Chronic neuroleptic of the human neuroleptic-induced dyskinetic syndrome treatment tardive dyskinesia (TD), they are often used in its study. -
Amisulpride Tablets I.P. SOLIAN® THERAPEUTIC CATEGORY Anti-Psychotic COMPOSITION Solian® 50 /100 /200 /400 Each Uncoated Tablet Contains Amisulpride IP
For the use only of a Registered Medical Practitioner (Psychiatrist) or a Hospital or a Laboratory Abridged Prescribing Information Amisulpride tablets I.P. SOLIAN® THERAPEUTIC CATEGORY Anti-psychotic COMPOSITION Solian® 50 /100 /200 /400 Each uncoated tablet contains Amisulpride IP. 50mg / 100mg / 200mg Each film coated tablet contains Amisulpride IP 400mg. THERAPEUTIC INDICATIONS Treatment of acute and chronic schizophrenic disorders, in which positive symptoms (such as delusions, hallucinations, and thought disorders) and/or negative symptoms (such as blunted affect, emotional and social withdrawal) are prominent, including patients characterised by predominant negative symptoms. DOSAGE AND ADMINISTRATION For acute psychotic episodes, oral doses between 400 and 800 mg/d are recommended. Doses above 1200 mg/d should not be used. For patients with mixed positive and negative symptoms, doses should be adjusted to obtain optimal control of positive symptoms. Maintenance treatment should be established individually with the minimally effective dose. For patients characterised by predominant negative symptoms, oral doses between 50 mg/d and 300 mg/d are recommended. Doses should be adjusted individually. Solian® can be administered once daily at oral doses up to 300 mg, higher doses should be administered bid. The Minimum effective dose should be used. Caution in elderly. Renal & Hepatic insufficiency: Dose should be reduced. Use of amisulpride from puberty to 18 years is not recommended. SAFETY-RELATED INFORMATION Contraindications: Hypersensitivity to amisulpride or to other ingredients of the product; concomitant prolactin- dependent tumours e.g. pituitary gland prolactinomas and breast cancer; phaeochromocytoma; children up to puberty; lactation; combinations with drugs which could induce torsades de pointes and levodopa. -
The Effects of Antipsychotic Treatment on Metabolic Function: a Systematic Review and Network Meta-Analysis
The effects of antipsychotic treatment on metabolic function: a systematic review and network meta-analysis Toby Pillinger, Robert McCutcheon, Luke Vano, Katherine Beck, Guy Hindley, Atheeshaan Arumuham, Yuya Mizuno, Sridhar Natesan, Orestis Efthimiou, Andrea Cipriani, Oliver Howes ****PROTOCOL**** Review questions 1. What is the magnitude of metabolic dysregulation (defined as alterations in fasting glucose, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride levels) and alterations in body weight and body mass index associated with short-term (‘acute’) antipsychotic treatment in individuals with schizophrenia? 2. Does baseline physiology (e.g. body weight) and demographics (e.g. age) of patients predict magnitude of antipsychotic-associated metabolic dysregulation? 3. Are alterations in metabolic parameters over time associated with alterations in degree of psychopathology? 1 Searches We plan to search EMBASE, PsycINFO, and MEDLINE from inception using the following terms: 1 (Acepromazine or Acetophenazine or Amisulpride or Aripiprazole or Asenapine or Benperidol or Blonanserin or Bromperidol or Butaperazine or Carpipramine or Chlorproethazine or Chlorpromazine or Chlorprothixene or Clocapramine or Clopenthixol or Clopentixol or Clothiapine or Clotiapine or Clozapine or Cyamemazine or Cyamepromazine or Dixyrazine or Droperidol or Fluanisone or Flupehenazine or Flupenthixol or Flupentixol or Fluphenazine or Fluspirilen or Fluspirilene or Haloperidol or Iloperidone -
Aripiprazole Augmentation of Clomipramine Therapy In
Dusunen Adam The Journal of Psychiatry and Neurological Sciences 2016;29:167-172 Case Report / Olgu Sunumu DOI: 10.5350/DAJPN2016290209 Aripiprazole Augmentation Filiz Izci1, Murat Yalcin2, Sumeyye Yasemin Kurtulus Calli2, of Clomipramine Therapy in Yagmur Sever3, Rabia Bilici3 1Istanbul Bilim University, Faculty of Medicine, Treatment-Resistant Department of Psychiatry, Istanbul - Turkey 2Kocaeli Derince Training and Research Hospital, Department of Psychiatry, Kocaeli - Turkey Obsessive-Compulsive 3Erenkoy Training and Research Hospital for Psychiatric and Neurological Disorders, Istanbul - Turkey Disorder: Case Series ABSTRACT Aripiprazole augmentation of clomipramine therapy in treatment-resistant obsessive-compulsive disorder: case series Obsessive-compulsive disorder (OCD) is a chronic disorder characterized by recurrent intrusive thoughts and repetitive rituals, causing significant distress and functional loss. Studies show evidence about serotonergic and dopaminergic mechanisms in neuropathogenesis of OCD. Selective serotonin re-uptake inhibitors (SSRI) are considered as first-line treatment in OCDs, but treatment resistance may occur in 40-60% of cases treated with SSRIs. Augmentation of antidepressants with atypical antipsychotics is an important treatment option in treatment-resistant patients with OCD. In this article, we aimed to present five OCD cases with treatment-resistance in which we obtained good outcomes, with addition of aripiprazole 10-30mg per day to clomipramine therapy. Address reprint requests to / Yazışma adresi: -
PRODUCT MONOGRAPH ELAVIL® Amitriptyline Hydrochloride Tablets
PRODUCT MONOGRAPH ELAVIL® amitriptyline hydrochloride tablets USP 10, 25, 50 and 75 mg Antidepressant AA PHARMA INC. DATE OF PREPARATION: 1165 Creditstone Road Unit #1 August 29, 2018 Vaughan, ON L4K 4N7 Control No.: 217626 1 PRODUCT MONOGRAPH ELAVIL® amitriptyline hydrochloride tablets USP 10, 25, 50, 75 mg THERAPEUTIC CLASSIFICATION Antidepressant ACTIONS AND CLINICAL PHARMACOLOGY Amitriptyline hydrochloride is a tricyclic antidepressant with sedative properties. Its mechanism of action in man is not known. Amitriptyline inhibits the membrane pump mechanism responsible for the re-uptake of transmitter amines, such as norepinephrine and serotonin, thereby increasing their concentration at the synaptic clefts of the brain. Amitriptyline has pronounced anticholinergic properties and produces EKG changes and quinidine-like effects on the heart (See ADVERSE REACTIONS). It also lowers the convulsive threshold and causes alterations in EEG and sleep patterns. Orally administered amitriptyline is readily absorbed and rapidly metabolized. Steady-state plasma concentrations vary widely and this variation may be genetically determined. Amitriptyline is primarily excreted in the urine, mostly in the form of metabolites, with some excretion also occurring in the feces. INDICATIONS AND CLINICAL USE ELAVIL® (amitriptyline hydrochloride) is indicated in the drug management of depressive illness. ELAVIL® may be used in depressive illness of psychotic or endogenous nature and in selected patients with neurotic depression. Endogenous depression is more likely to be alleviated than are other depressive states. ELAVIL® ®, because of its sedative action, is also of value in alleviating the anxiety component of depression. As with other tricyclic antidepressants, ELAVIL® may precipitate hypomanic episodes in patients with bipolar depression. These drugs are not indicated in mild depressive states and depressive reactions. -
Reference 8 Huang Repurposing Psychiatric Drugs for Cancer 18
Cancer Letters 419 (2018) 257e265 Contents lists available at ScienceDirect Cancer Letters journal homepage: www.elsevier.com/locate/canlet Mini-review Repurposing psychiatric drugs as anti-cancer agents * Jing Huang a, b, c, d, Danwei Zhao e, Zhixiong Liu a, Fangkun Liu a, a Department of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha, China b Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China c Mental Health Institute of the Second Xiangya Hospital, Central South University, Chinese National Clinical Research Center for Mental Disorders (Xiangya), Changsha, Hunan, 410011, China d Chinese National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, 410011, China e Xiangya Medical School, Central South University, Changsha, Hunan, China article info abstract Article history: Cancer is a major public health problem and one of the leading contributors to the global disease burden. Received 10 November 2017 The high cost of development of new drugs and the increasingly severe burden of cancer globally have Received in revised form led to increased interest in the search and development of novel, affordable anti-neoplastic medications. 17 January 2018 Antipsychotic drugs have a long history of clinical use and tolerable safety; they have been used as good Accepted 19 January 2018 targets for drug repurposing. Being used for various psychiatric diseases for decades, antipsychotic drugs are now reported to have potent anti-cancer properties against a wide variety of malignancies in addition Keywords: to their antipsychotic effects. In this review, an overview of repurposing various psychiatric drugs for Antipsychotic drugs Drug repurposing cancer treatment is presented, and the putative mechanisms for the anti-neoplastic actions of these Cancer treatment antipsychotic drugs are reviewed. -
Drug Class Review on Atypical Antipsychotic Drugs
Drug Class Review on Atypical Antipsychotic Drugs Final Report April 2006 The purpose of this report is to make available information regarding the comparative effectiveness and safety profiles of different drugs within pharmaceutical classes. Reports are not usage guidelines, nor should they be read as an endorsement of, or recommendation for, any particular drug, use or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports. Marian S. McDonagh, PharmD Kim Peterson, MS Susan Carson, MPH Oregon Evidence-based Practice Center Oregon Health & Science University Mark Helfand, MD, MPH, Director Copyright © 2006 by Oregon Health & Science University Portland, Oregon 97201. All rights reserved. Final Report Update 1 Drug Effectiveness Review Project TABLE OF CONTENTS INTRODUCTION............................................................................................................. 5 Scope and Key Questions ......................................................................................................13 METHODS .................................................................................................................... 15 Literature Search ....................................................................................................................15 Study Selection .......................................................................................................................15 Data Abstraction .....................................................................................................................15 -
Download Product Insert (PDF)
PRODUCT INFORMATION Chlorprothixene (hydrochloride) Item No. 20772 CAS Registry No.: 6469-93-8 Formal Name: (3Z)-3-(2-chloro-9H-thioxanthen-9-ylidene)-N,N- N dimethyl-1-propanamine, monohydrochloride Synonyms: cis-Chlorprothixene, NSC 169899 MF: C18H18ClNS • HCl Cl FW: 352.3 Purity: ≥98% UV/Vis.: λmax: 230, 270, 329 nm S Supplied as: A crystalline solid • HCl Storage: -20°C Stability: As supplied, 2 years from the QC date provided on the Certificate of Analysis, when stored properly Laboratory Procedures Chlorprothixene (hydrochloride) is supplied as a crystalline solid. A stock solution may be made by dissolving the chlorprothixene (hydrochloride) in the solvent of choice. Chlorprothixene (hydrochloride) is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide, which should be purged with an inert gas. The solubility of chlorprothixene (hydrochloride) in these solvents is approximately 30 mg/ml. Further dilutions of the stock solution into aqueous buffers or isotonic saline should be made prior to performing biological experiments. Ensure that the residual amount of organic solvent is insignificant, since organic solvents may have physiological effects at low concentrations. Organic solvent-free aqueous solutions of chlorprothixene (hydrochloride) can be prepared by directly dissolving the crystalline solid in aqueous buffers. The solubility of chlorprothixene (hydrochloride) in PBS, pH 7.2, is approximately 10 mg/ml. We do not recommend storing the aqueous solution for more than one day. Description 1 Chlorprothixene is a thioxanthine antipsychotic that functions by antagonizing dopamine D2 receptors. It 2 can block a subset of GABAA receptors in rat cortex that is also blocked by clozapine (Item No. -
SAFETY of the ELECTROCONVULSIVE THERAPY and AMISULPRIDE COMBINATION Rozália Takács1, Zsolt Iványi2, Gabor S
Psychiatria Danubina, 2013; Vol. 25, No. 1, pp 76-79 Brief report © Medicinska naklada - Zagreb, Croatia SAFETY OF THE ELECTROCONVULSIVE THERAPY AND AMISULPRIDE COMBINATION Rozália Takács1, Zsolt Iványi2, Gabor S. Ungvari3, 4 & Gábor Gazdag1,5 1Department of Psychiatry and Psychotherapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary 2 Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary 3University of Notre Dame, Australia 4Marian Centre, Perth, Australia 5Consultation–Liaison Psychiatric Service, Szent István and Szent László Hospitals, Budapest, Hungary received: 21.10.2011; revised: 16.1.2012; accepted: 2.12.2012 SUMMARY Background: Electroconvulsive therapy is frequently considered when pharmacotherapy is ineffective. In such cases the combination of the two treatment modalities are commonly used. Amisulpiride, a second generation antipsychotic drug is used in the treatment of schizophrenia and psychotic depression. When amisulpiride is ineffective as a monotherapy, combination with ECT could be an option to enhance its efficacy. To the best of our knowledge, to date there have been no data about the safety of this combination. Subjects and methods: Medical notes of all patients who were given ECT while on amisulpiride were selected from the archives of the Department of Psychiatry, Semmelweis University Medical School, Budapest, covering a 10-year period. A randomly selected matched control group was formed from patients who underwent ECT but were not taking amisulpiride. Patients in both groups also received a variety of psychotropic drugs other than amisulpide. Side effects were compared between the two groups of patients. Results: Twenty patients received amisulpride with ECT. The most common side effects were headache, hypertension, tachycardia, nausea, dizziness, confusion, psychomotor agitation, sialorrhea, and prolonged seizure activity. -
Drug Screening: Actual Status, Pitfalls and Suggestions for Improvement Drogenscreening: Gegenwa¨ Rtiger Stand, Fehlermo¨ Glichkeiten Und Verbesserungsvorschla¨Ge
J Lab Med 2004;28(4):317–325 ᮊ 2004 by Walter de Gruyter • Berlin • New York 2004/03304 Drug Monitoring und Toxikologie Redaktion: V. W. Armstrong Drug screening: Actual status, pitfalls and suggestions for improvement Drogenscreening: Gegenwa¨ rtiger Stand, Fehlermo¨ glichkeiten und Verbesserungsvorschla¨ge Wolf R. Ku¨ lpmann* pretierbar. In Wirklichkeit mu¨ ssen viele Aspekte beru¨ ck- sichtigt werden, um einen aussagekra¨ ftigen Befund zu Klinische Chemie, Medizinische Hochschule Hannover, erhalten, z.B. Pra¨ analytik, Spezifita¨ t und Empfindlichkeit Hannover, Germany des Verfahrens oder Qualita¨ tssicherung. Obwohl die Abstract mechanisierten Meßverfahren naturgema¨ ß quantitative Ergebnisse liefern, wird aufgezeigt, daß es sich in der Immunoassays for drug screening are often regarded as Regel empfiehlt, qualitative Befunde zu erstellen. Die procedures which are easily performed and interpreted. Verfahren erlauben aber im Gegensatz zu den auch fu¨r But in fact, many aspects have to be considered to diese Zwecke verwendeten Teststreifen die Entschei- obtain a meaningful result. Among these are sampling, dungsgrenze (cut-off) der jeweiligen Fragestellung anzu- specificity and sensitivity of assays, and quality assess- passen, z.B. bei akuter Intoxikation, chronischem Abusus ment. Although the mechanised procedures yield quan- oder U¨ berwachung des Drogenentzugs. titative results, there are good reasons to generally report Ein schwerwiegender Nachteil von Immunoassays zum qualitative findings. The mechanised procedures allow Nachweis von Amphetamin und a¨ hnlichen Substanzen, the adjustment of the cut-off concentration to the clinical Barbituraten, Benzodiazepinen und Opiaten besteht dar- setting, e.g. in the case of acute intoxication, chronic in, daß eine starke Kreuzreaktivita¨ t des Antiko¨ rpers abuse or drug withdrawal, an important advantage as gegenu¨ ber pharmakologisch wenig wirksamen Verbin- compared to test strips.