Dopamine Antagonist Prescribing Practices in Patients with Parkinson Disease
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Management of Side Effects of Antipsychotics
Management of side effects of antipsychotics Oliver Freudenreich, MD, FACLP Co-Director, MGH Schizophrenia Program www.mghcme.org Disclosures I have the following relevant financial relationship with a commercial interest to disclose (recipient SELF; content SCHIZOPHRENIA): • Alkermes – Consultant honoraria (Advisory Board) • Avanir – Research grant (to institution) • Janssen – Research grant (to institution), consultant honoraria (Advisory Board) • Neurocrine – Consultant honoraria (Advisory Board) • Novartis – Consultant honoraria • Otsuka – Research grant (to institution) • Roche – Consultant honoraria • Saladax – Research grant (to institution) • Elsevier – Honoraria (medical editing) • Global Medical Education – Honoraria (CME speaker and content developer) • Medscape – Honoraria (CME speaker) • Wolters-Kluwer – Royalties (content developer) • UpToDate – Royalties, honoraria (content developer and editor) • American Psychiatric Association – Consultant honoraria (SMI Adviser) www.mghcme.org Outline • Antipsychotic side effect summary • Critical side effect management – NMS – Cardiac side effects – Gastrointestinal side effects – Clozapine black box warnings • Routine side effect management – Metabolic side effects – Motor side effects – Prolactin elevation • The man-in-the-arena algorithm www.mghcme.org Receptor profile and side effects • Alpha-1 – Hypotension: slow titration • Dopamine-2 – Dystonia: prophylactic anticholinergic – Akathisia, parkinsonism, tardive dyskinesia – Hyperprolactinemia • Histamine-1 – Sedation – Weight gain -
Appendix 13C: Clinical Evidence Study Characteristics Tables
APPENDIX 13C: CLINICAL EVIDENCE STUDY CHARACTERISTICS TABLES: PHARMACOLOGICAL INTERVENTIONS Abbreviations ............................................................................................................ 3 APPENDIX 13C (I): INCLUDED STUDIES FOR INITIAL TREATMENT WITH ANTIPSYCHOTIC MEDICATION .................................. 4 ARANGO2009 .................................................................................................................................. 4 BERGER2008 .................................................................................................................................... 6 LIEBERMAN2003 ............................................................................................................................ 8 MCEVOY2007 ................................................................................................................................ 10 ROBINSON2006 ............................................................................................................................. 12 SCHOOLER2005 ............................................................................................................................ 14 SIKICH2008 .................................................................................................................................... 16 SWADI2010..................................................................................................................................... 19 VANBRUGGEN2003 .................................................................................................................... -
Yorkshire Palliative Medicine Clinical Guidelines Group Guidelines on the Use of Antiemetics Author(S): Dr Annette Edwards (Chai
Yorkshire Palliative Medicine Clinical Guidelines Group Guidelines on the use of Antiemetics Author(s): Dr Annette Edwards (Chair) and Deborah Royle on behalf of the Yorkshire Palliative Medicine Clinical Guidelines Group Overall objective : To provide guidance on the evidence for the use of antiemetics in specialist palliative care. Search Strategy: Search strategy: Medline, Embase and Cinahl databases were searched using the words nausea, vomit$, emesis, antiemetic and drug name. Review Date: March 2008 Competing interests: None declared Disclaimer: These guidelines are the property of the Yorkshire Palliative Medicine Clinical Guidelines Group. They are intended to be used by qualified, specialist palliative care professionals as an information resource. They should be used in the clinical context of each individual patient’s needs. The clinical guidelines group takes no responsibility for any consequences of any actions taken as a result of using these guidelines. Contact Details: Dr Annette Edwards, Macmillan Consultant in Palliative Medicine, Department of Palliative Medicine, Pinderfields General Hospital, Aberford Road, Wakefield, WF1 4DG Tel: 01924 212290 E-mail: [email protected] 1 Introduction: Nausea and vomiting are common symptoms in patients with advanced cancer. A careful history, examination and appropriate investigations may help to infer the pathophysiological mechanism involved. Where possible and clinically appropriate aetiological factors should be corrected. Antiemetics are chosen based on the likely mechanism and the neurotransmitters involved in the emetic pathway. However, a recent systematic review has highlighted that evidence for the management of nausea and vomiting in advanced cancer is sparse. (Glare 2004) The following drug and non-drug treatments were reviewed to assess the strength of evidence for their use as antiemetics with particular emphasis on their use in the palliative care population. -
Clinical Guideline Drug/Drug Class: Antipsychotics Prepared By
MassHealth Drug Utilization Review Program Commonwealth Medicine University of Massachusetts Medical School P.O. Box 2586 Worcester MA, 01613-2586 Clinical Guideline Drug/Drug Class: Antipsychotics Prepared by: Drug Utilization Review Program Prepared for: MassHealth Pharmacy Program Purpose: The purpose of this guideline is to clarify the procedures for approving and denying prior authorization (PA) requests for: Polypharmacy with two or more antipsychotics for members ≥ 18 years old (including first- generation [typical] and second-generation [atypical]) for greater than 60 days (excluding clozapine and injectable formulations) Orally disintegrating dosage forms and Versacloz® (clozapine) oral suspension Medication exceeding defined quantity limits Fanapt® (iloperidone), Invega® (paliperidone), Latuda® (lurasidone), Rexulti® (brexpiprazole), Saphris® (asenapine), and Vraylar® (cariprazine) for members of all ages and all quantities Abilify® (aripiprazole) and Seroquel XR® (quetiapine extended-release) for members 18 years of age and older and all quantities Background: Since 2003, MassHealth has determined that oral second-generation (atypical) antipsychotics (with the exception of clozapine and injectables) would require prior authorization for polypharmacy, defined as two or more second-generation (atypical) antipsychotics for greater than 60 days. Clozapine is excluded from the polypharmacy requirement because the guidelines for the treatment of schizophrenia recognize that combinations including clozapine have been reported. 1 In 2016, the adult antipsychotic polypharmacy criteria was updated and the PA restriction was expanded to include first-generation (typical), and second-generation (atypical) antipsychotics, excluding clozapine and injectable formulations. Orally disintegrating tablets (ODT) of aripiprazole, clozapine, olanzapine and risperidone, as well as Versacloz® (clozapine) oral suspension also require PA since there are more cost-effective alternatives available. -
Heat Related Illness in Psychotropic Medication Users
Common psychotropic medications which Prevention of Heat can impair your response to heat Related Illness Trade Name Generic Name Abilify aripiprazole During periods of high temperature (85º Asendin amoxapine and above) and humidity, there are things Artane trihexyphenidyl everyone, particularly people at high risk, Aventil, Pamelor nortriptyline should do to lessen the chances of heat Clozaril clozapine illness. Cogentin benztropine Compazine prochlorperazine ¾ Try to stay cool. Desyrel trazodone • Stay in air conditioned areas if Elavil, Limbitrol, possible. If you do not have air Triavil amitriptyline conditioning at home, go to a Eskalith, Lithobid, shopping mall or public library. Lithonate lithium • Keep windows shut and draperies, Geodon ziprasidone shades, or blinds drawn during the Haldol haloperidol heat of the day. Loxitane loxapine • Open windows in the evening or Ludiomil maprotiline night hours when the air outside is Mellaril thioridazine Heat Related Illness cooler. Moban molindone • Move to cooler rooms during the Navane thiothixene in heat of the day. Norpramin desipramine Psychotropic ¾ Avoid overexertion and outdoor Phenergan promethazine activity, particularly during warmer Prolixin fluphenazine Medication Users periods of the day. Risperdal risperidone ¾ Apply sunscreen and lotion as needed. Serentil mesoridazine Seroquel quetiapine ¾ Drink plenty of fluids (avoid coffee, tea, and alcohol). Sinequan doxepin ¾ Dress in loose fitting, light colored Stelazine trifluoperazine clothing. Wear a hat, sunglasses, and Thorazine chlorpromazine other protective clothing. Tofranil imipramine ¾ Take a cool shower or bath. Trilafon perphenazine ¾ Lose weight if you are overweight. Wellbutrin buproprion ¾ Eat regular meals to ensure that you Zyprexa olanzapine Ohio Department of Mental Health have adequate salt and fluids. *Note: This is not an all inclusive list. -
S1 Table. List of Medications Analyzed in Present Study Drug
S1 Table. List of medications analyzed in present study Drug class Drugs Propofol, ketamine, etomidate, Barbiturate (1) (thiopental) Benzodiazepines (28) (midazolam, lorazepam, clonazepam, diazepam, chlordiazepoxide, oxazepam, potassium Sedatives clorazepate, bromazepam, clobazam, alprazolam, pinazepam, (32 drugs) nordazepam, fludiazepam, ethyl loflazepate, etizolam, clotiazepam, tofisopam, flurazepam, flunitrazepam, estazolam, triazolam, lormetazepam, temazepam, brotizolam, quazepam, loprazolam, zopiclone, zolpidem) Fentanyl, alfentanil, sufentanil, remifentanil, morphine, Opioid analgesics hydromorphone, nicomorphine, oxycodone, tramadol, (10 drugs) pethidine Acetaminophen, Non-steroidal anti-inflammatory drugs (36) (celecoxib, polmacoxib, etoricoxib, nimesulide, aceclofenac, acemetacin, amfenac, cinnoxicam, dexibuprofen, diclofenac, emorfazone, Non-opioid analgesics etodolac, fenoprofen, flufenamic acid, flurbiprofen, ibuprofen, (44 drugs) ketoprofen, ketorolac, lornoxicam, loxoprofen, mefenamiate, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, pranoprofen, proglumetacin, sulindac, talniflumate, tenoxicam, tiaprofenic acid, zaltoprofen, morniflumate, pelubiprofen, indomethacin), Anticonvulsants (7) (gabapentin, pregabalin, lamotrigine, levetiracetam, carbamazepine, valproic acid, lacosamide) Vecuronium, rocuronium bromide, cisatracurium, atracurium, Neuromuscular hexafluronium, pipecuronium bromide, doxacurium chloride, blocking agents fazadinium bromide, mivacurium chloride, (12 drugs) pancuronium, gallamine, succinylcholine -
Action of LSD on Supersensitive Mesolimbic Dopamine Receptors
PROCEEDINGS OF THE B.P.S., 15th-17th SEPTEMBER, 1975 291P Action of LSD on supersensitive The rotation produced by LSD is therefore mesolimbic dopamine receptors probably due to an action on striatal dopamine receptors. P.H. KELLY To investigate whether LSD can act as an agonist at mesolimbic dopamine receptors we Psychological Laboratory, Downing St., Cambridge and recorded its effect in rats with bilateral 6-OHDA M. R. C Unit of Neurochemical Pharmacology, Medical lesions of the nucleus accumbens. These animals School, Hills Road, Cambridge show a greatly enhanced stimulation of locomotor activity when injected with dopamine agonists Since Ungerstedt & Arbuthnott (1970) described such as apomorphine (Kelly, Seviour & Iversen, the amphetamine-induced rotation of rats with 1975) or N-n-propylnorapomorphine (Kelly, Miller unilateral 6-hydroxydopamine (6-OHDA) lesions of & Neumeyer, 1975) compared to sham-operated the substantia nigra this in vivo preparation has animals, which may be due to supersensitivity of been widely used to study the effects of drugs on the denervated mesolimbic DA receptors. LSD dopaminergic mechanism in the brain. Recently it (1.0 mg/kg i.p.), like apomorphine (1.0 mg/kg has been shown that LSD, like the dopamine i.p.), produced a marked stimulation of locomotor agonist apomorphine, produces rotation towards activity in these animals although this dose did not the unlesioned side (Pieri, Pieri & Haefely, 1974) increase the locomotor activity of control rats. and it was suggested that LSD can act as a The non-hallucinogen (+)-bromo-lysergic acid dopamine agonist. Since 6-OHDA lesions of the diethylamide (2.0 mg/kg i.p.) did not stimulate substantia nigra which destroy the nigrostriatal locomotor activity in 6-OHDA treated rats. -
Evidence for Effective Acute Attack Treatment in Migraine
Turkish Journal of Medical Sciences Turk J Med Sci (2017) 47: 343-347 http://journals.tubitak.gov.tr/medical/ © TÜBİTAK Research Article doi:10.3906/sag-1601-195 Metoclopramide inhibits trigeminovascular activation: evidence for effective acute attack treatment in migraine 1,2,3 1,3 3,4 1,3, Hacer DOĞANAY AYDIN , Doğa VURALLI , Didem Tuba AKÇALI , Hayrunnisa BOLAY * 1 Department of Neurology, Faculty of Medicine, Gazi University, Ankara, Turkey 2 Department of Neurology, Konya Training and Research Hospital, Konya, Turkey 3 Neuropsychiatry Center, Faculty of Medicine, Gazi University, Ankara, Turkey 4 Department of Anesthesiology and Reanimation, Faculty of Medicine, Gazi University, Ankara, Turkey Received: 01.02.2016 Accepted/Published Online: 08.05.2016 Final Version: 27.02.2017 Background/aim: Metoclopramide is an effective and commonly used medication in acute migraine treatment but an experimental evidence base is lacking. We aimed to investigate the antimigraine effect of metoclopramide in a migraine model and whether the analgesic effect of metoclopramide was likely to be 2D receptor-mediated. Materials and methods: Cortical spreading depression (CSD) was used to model migraine in adult male Wistar rats. Five CSDs were induced by pinprick. Metoclopramide (two different doses), raclopride, or 0.9% saline were administered 30 min before CSD induction. Two hours after the experiments, brain tissues were examined for c-fos activation. Results: In metoclopramide groups brain stem c-fos expression was significantly lower than in the CSD side of the saline group (P = 0.002). In the raclopride group, ipsilateral brain stem c-fos expression was also lower than in the saline group (P = 0.002). -
Weight Gain Associated with Antipsychotic Drugs
Rohan Ganguli Weight Gain Associated With Antipsychotic Drugs Rohan Ganguli, M.D. © CopyrightWeight gain has been 2000 reported Physicians with nearly every antipsychotic Postgraduate drug on the market Press, (molindone Inc.is an exception). Weight gain occurs no matter what the patient’s age, sex, or race and is seen with both oral and depot drug formulations. Numerous studies have found that patients gain weight when treated with a conventional antipsychotic, such as chlorpromazine, fluphenazine, and haloperidol. The newer, novel antipsychotics offer advantages over conventional antipsychotics, especially a relative lack of extrapyramidal symptoms, but some still have the disadvantage of causing weight gain. Clozapine and olanzapine in particular appear to cause substantial weight gain, much more so than do most conven- tional neuroleptics and novel agents such as risperidone. Given the risks to health and treatment com- pliance associated with weight gain and obesity, clinicians should monitor weight during the course of antipsychotic therapy and consider switching agents if excessive weight gain occurs. (J Clin Psychiatry 1999;60[suppl 21]:20–24) One personal copy may be printed e have known for some time that treatment with CONVENTIONAL NEUROLEPTICS Wantipsychotic drugs is associated with weight gain. A few years after the first neuroleptic medications One of the earliest studies to examine weight gain asso- were introduced, researchers were reporting clinically sig- ciated with antipsychotic drugs in a large number of pa- nificant -
Sex Differences in Serotonergic and Dopaminergic Mediation of LSD Discrimination in Rats
Western Michigan University ScholarWorks at WMU Dissertations Graduate College 8-2017 Sex Differences in Serotonergic and Dopaminergic Mediation of LSD Discrimination in Rats Keli A. Herr Western Michigan University, [email protected] Follow this and additional works at: https://scholarworks.wmich.edu/dissertations Part of the Psychology Commons Recommended Citation Herr, Keli A., "Sex Differences in Serotonergic and Dopaminergic Mediation of LSD Discrimination in Rats" (2017). Dissertations. 3170. https://scholarworks.wmich.edu/dissertations/3170 This Dissertation-Open Access is brought to you for free and open access by the Graduate College at ScholarWorks at WMU. It has been accepted for inclusion in Dissertations by an authorized administrator of ScholarWorks at WMU. For more information, please contact [email protected]. SEX DIFFERENCES IN SEROTONERGIC AND DOPAMINERGIC MEDIATION OF LSD DISCRIMINATION IN RATS by Keli A Herr A dissertation submitted to the Graduate College in partial fulfillment of the requirements for the degree of Doctor of Philosophy Psychology Western Michigan University August 2017 Doctoral Committee: Lisa Baker, Ph.D., Chair Cynthia Pietras, Ph.D. Heather McGee, Ph.D. Missy Peet, Ph.D. SEX DIFFERENCES IN SEROTONERGIC AND DOPAMINERGIC MEDIATION OF LSD DISCRIMINATION IN RATS Keli A. Herr, Ph.D. Western Michigan University After decades of opposition, a resurgence of interest in the psychotherapeutic potential of LSD is gaining acceptance in the medical community. Future acceptance of LSD as a psychotherapeutic adjuvant may be predicated on knowledge about its neural mechanisms of action. Preclinical drug discrimination assay offers an invaluable model to determine the neural mechanisms underlying LSD’s interoceptive stimulus effects. -
Drugs for Parkinson's Disease
Australian Prescriber Vol. 24 No. 4 2001 Drugs for Parkinson’s disease V.S.C. Fung, M.A. Hely, Department of Neurology, G. De Moore, Department of Psychiatry and J.G.L. Morris, Department of Neurology, Westmead Hospital, Westmead, New South Wales SYNOPSIS Levodopa commonly causes nausea, especially when treatment Levodopa is the most effective drug available for treating begins. This nausea results from the conversion of levodopa to the motor symptoms of idiopathic Parkinson’s disease. It dopamine which stimulates the dopamine receptors in the area is usually combined with a peripheral dopa decarboxylase postrema (‘vomiting centre’) in the brainstem, a structure which inhibitor. Early treatment with dopamine agonists can lies outside the blood-brain barrier. The nausea is minimised by reduce the risk of developing dyskinesia. Dopamine agonists introducing levodopa slowly, starting with a low dose, taking it and catechol-O-methyltransferase inhibitors can with food and giving it in combination with a peripheral dopa significantly reduce motor fluctuations. Amantadine decarboxylase inhibitor such as carbidopa or benserazide. A reduces the severity of dyskinesia in some patients. No minimum daily dose of 75 mg is necessary to adequately inhibit treatment has been proven to delay disease progression. the production of dopamine outside the blood-brain barrier. Metoclopramide and prochlorperazine should be avoided as Index words: amantadine, dopamine, entacapone, they are dopamine antagonists and make parkinsonism worse. levodopa, selegiline. If an antiemetic is required, domperidone 10–20 mg three times (Aust Prescr 2001;24:92–5) daily is the drug of choice as it is a dopamine antagonist which does not cross the blood-brain barrier. -
Sustained Administration of Pramipexole Modifies the Spontaneous Firing of Dopamine, Norepinephrine, and Serotonin Neurons in the Rat Brain
Neuropsychopharmacology (2009) 34, 651–661 & 2009 Nature Publishing Group All rights reserved 0893-133X/09 $32.00 www.neuropsychopharmacology.org Sustained Administration of Pramipexole Modifies the Spontaneous Firing of Dopamine, Norepinephrine, and Serotonin Neurons in the Rat Brain ,1 1 1,2 O Chernoloz* , M El Mansari and P Blier 1 2 Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, Canada Pramipexole (PPX) is a D2/D3 receptor agonist that has been shown to be effective in the treatment of depression. Serotonin (5-HT), norepinephrine (NE) and dopamine (DA) systems are known to be involved in the pathophysiology and treatment of depression. Due to reciprocal interactions between these neuronal systems, drugs selectively targeting one system-specific receptor can indirectly modify the firing activity of neurons that contribute to firing patterns in systems that operate via different neurotransmitters. It was thus hypothesized that PPX would alter the firing rate of DA, NE and 5-HT neurons. To test this hypothesis, electrophysiological experiments were carried out in anesthetized rats. Subcutaneously implanted osmotic minipumps delivered PPX at a dose of 1 mg/kg per day for 2 or 14 days. After a 2-day treatment with PPX the spontaneous neuronal firing of DA neurons was decreased by 40%, NE neuronal firing by 33% and the firing rate of 5-HT neurons remained unaltered. After 14 days of PPX treatment, the firing rate of DA had recovered as well as that of NE, whereas the firing rate of 5-HT neurons was increased by 38%.