DOCSLIB.ORG

PHG0702REV Lexa 11 19Hcsc 2/12/08 1:56 PM Page 1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
PHG0702REV Lexa 11 19Hcsc 2/12/08 1:56 PM Page 1 PHG0702REV Lexa 11_19hcsc 2/12/08 1:56 PM Page 1 R 200 BE 7 M E C E D ® PRODUCT INFORMATION GUIDE JOHN BAVOSI / PHOTO RESEARCHERS, INC LEXAPRO® (escitalopram oxalate) in the Treatment of Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) SPECIAL ADVERTISING SECTION This Product Information Guide is supported by a grant from Forest Pharmaceuticals, Inc. PHG0702 PHG0702REV Lexa 11_19hcsc 2/12/08 1:56 PM Page 2 LEXAPRO® (escitalopram oxalate) in the Treatment of Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) JOHN BAVOSI / PHOTO RESEARCHERS, INC Major Depressive Disorder sible risk factors for the development of MDD are an Major Depressive Disorder (MDD) is a serious illness increased susceptibility to develop a major depressive with significant morbidity and mortality risks, char- episode due to genetic factors and/or triggers such as acterized by disabling feelings of sadness and worth- a death or other significant loss5,6. The importance of lessness. The lifetime prevalence of MDD is more than the role of genetics, biological factors, and environ- 16% in the US adult population1. The DSM-IV-TR mental triggers may be different for each patient and criteria for diagnosis includes a depressed mood or have yet to be completely understood. loss of interest or pleasure in daily activities for at least a two-week period, representing a change from a Generalized Anxiety Disorder (GAD) person’s normal mood. The depressive symptoms must Generalized Anxiety Disorder (GAD) is a chronic, debil- have a negative impact on daily functioning. A itating condition characterized by overwhelming and patient with MDD must exhibit at least five of the uncontrollable anxiety. Lifetime prevalence of GAD in following symptoms most of the day, nearly every the U.S. is approximately 5%7. The DSM-IV-TR crite- day: depressed or irritable mood, loss of interest or plea- ria for diagnosis includes excessive anxiety and worry for sure in activities, sudden change in weight or appetite, more than six months with at least three additional symp- sleeping difficulties, agitation, fatigue, feelings of worth- toms, including restlessness, fatigue, difficulty in con- lessness or inappropriate guilt, difficulty concentrating centrating, irritability, muscle tension, and impaired sleep or making decisions, or frequent thoughts of death or cycle2. suicide2. In addition, up to 90% of depressed patients As in MDD, the exact cause of GAD is unclear. also experience symptoms of anxiety3. Researchers speculate the symptoms of GAD are a result Although the exact cause of MDD is unknown, of a combination of genetic, biochemical, and/or envi- researchers continue to study the biochemical basis ronmental triggers. Neurotransmitters most likely involved for changes in mood by examining neurotransmitters in anxiety-based disorders are gamma-aminobutyric acid and the neural communications they control4. Theo- (GABA), serotonin, dopamine, and epinephrine. Sero- ries of the cause of brain-chemical imbalances center tonin deficiencies appear to play a significant role in on the abnormal regulation of serotonergic (5-HT) the etiology of anxiety as well as depression. neurotransmission. Abnormal transmission of cholin- MDD and GAD are often coexisting conditions. If ergic and catecholaminergic neurotransmitters may also patients do not meet the criteria for a dual diagnosis, be part of the puzzle, as well as biochemical abnor- they are likely to have overlapping symptoms of depres- malities within the neuroendocrine system. sion and anxiety. As a result, serotonin reuptake inhibitors In addition to biochemical abnormalities, other pos- are ideal agents for the effective treatment of these patients. PHG0702 U.S. PHARMACIST DECEMBER 2007 2 PHG0702REV Lexa 11_19hcsc 2/12/08 1:56 PM Page 3 LEXAPRO® (ESCITALOPRAM OXALATE) Treatment serotonin transport8. Current treatment for both MDD and GAD includes Therefore, isolating the S-enantiomer produces a behavioral as well as drug therapy. In general, non- more potent antidepressant than that of the racemate drug treatment (psychotherapy) for both MDD and citalopram, since the removal of the R-enantiomer GAD includes psychotherapy techniques such as cog- removes more than merely an inactive ingredient9. nitive-behavioral therapy and interpersonal therapy. Cognitive-behavioral therapy helps change the think- Pharmacokinetics ing patterns that support mood disturbances; behav- The pharmacokinetic studies of Lexapro are linear ioral therapy gives people choices as to how they can and dose-proportional in the dosage range of 10 to 20 react to environmental triggers that produce depres- mg/day. Biotransformation is primarily hepatic, and sion or anxiety. the terminal half-life is approximately 27-32 hours, Drug treatment for MDD includes the use of tricyclic allowing for once daily dosing. Elderly patients and antidepressants (TCAs), monoamine oxidase inhibitors those with hepatic impairment should begin with the (MAOIs), and the newest class of antidepressants known 10 mg daily dose. No dosage adjustment is required as the serotonin reuptake inhibitors (SRIs). There are in patients with mild to moderate renal impairment10. two types of SRIs: selective serotonin reuptake inhibitors, Absorption is not affected by food. Binding to plasma or SSRIs, including escitalopram (Lexapro), citalopram protein is low (approximately 56%), allowing for use (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), parox- with highly protein-bound drugs12. etine (Paxil), and sertraline (Zoloft); and selective sero- tonin-norepinephrine reuptake inhibitors, or SNRIs, Efficacy in Clinical Trials including duloxetine (Cymbalta) and venlafaxine (Effexor). In patients who met the DSM-IV-TR criteria for a diag- The mechanism of action of these “second generation” nosis of either MDD or GAD, the safety and efficacy SRIs is not well understood. They are most likely to effect of a short term, eight-week course of Lexapro has serotonin, norepinephrine or dopamine activity in the been proven in multiple placebo-controlled studies, central nervous system. Serotonin reuptake inhibitors using the Montgomery-Asberg Depression Rating Scale have been shown to inhibit serotonin reuptake into the (MADRS) to measure efficacy in MDD and the Hamil- presynaptic cell, resulting in increased concentrations in ton Anxiety Scale (HAM-A) to measure efficacy in the synaptic cleft. The SSRI class is considered first line GAD10. in the treatment of depression due to the superior In general, Lexapro was well tolerated in clinical tri- safety profile of these agents compared to older com- als for safety and efficacy in both indications, MDD pounds, although their efficacy is comparable1. Gener- and GAD. ally speaking, the agents within in the SSRI class The most common adverse effects observed in the appear to be similar in average comparative efficacy 715 patients with MDD treated with Lexapro in placebo- and comparative effectiveness1. controlled trials were insomnia, ejaculation disorder, In addition to the use of approved SRIs, TCAs, and nausea, sweating, increased fatigue, and somnolence10.* MAOIs, drug treatment options for GAD include the The most common adverse effects observed in the use of benzodiazepines, azapirones, and beta-blockers 1. 429 patients with GAD treated with Lexapro in placebo- controlled trials were nausea, ejaculation disorder, insom- Focus on Lexapro (escitalopram) nia, fatigue, decreased libido, and anorgasmia10.* Lexapro is indicated for the treatment of major depres- * The incidence of these adverse effects was 5% or sive disorder and generalized anxiety disorder in adult greater, and approximately twice that observed in patients (age 18 years or older). the patients receiving placebo. Pharmacology Comparison to Citalopram Escitalopram (Lexapro), the pure S-enantiomer of In a meta-analysis of five clinical studies (1,545 patients) the racemic compound citalopram (Celexa), is the phar- comparing the effects of citalopram with Lexapro on macologically active enantiomer of the racemate. In MADRS scores at week eight of treatment, Lexapro studies in rats, the R-enantiomer of citalopram has provided an additional treatment effect of a 1.25 point been shown to inhibit the effect of escitalopram on reduction on the MADRS score compared with patients U.S. PHARMACIST DECEMBER 2007 3 PHG0702REV Lexa 11_19hcsc 2/12/08 1:56 PM Page 4 LEXAPRO® (ESCITALOPRAM OXALATE) on citalopram1. In one prospective head-to-head ing serotonin reuptake inhibitor drugs, it is advised that comparison trial, Lexapro 20 mg/day also led to sig- patients be monitored for adverse symptoms. When- nificantly greater response and remission rates than ever possible, the dose of these agents should be grad- citalopram 40 mg/day9. ually reduced10. A clinical trial by Zimbroff and colleagues studied depressed patients who were randomized to receive eight Drug Interactions weeks of lead-in treatment with citalopram, fluoxetine, Pharmacokinetic studies of the metabolism of Lexapro paroxetine or sertraline11. Patients who were consid- and its metabolites have shown these are unlikely to ered non-responders (MARDS >12) at the end of eight have significant inhibitory effects on the human weeks (N=139) were then treated with open label Lexapro cytochrome P450 enzyme system. As a result, there is therapy (10-20 mg/day) for an additional eight little likelihood of clinically significant interactions weeks. Of the 136 patients who were evaluated for effi- between Lexapro and other
Load more

Recommended publications
  • Efficacy of Treatments for Patients with Obsessive-Compulsive Disorder: a Systematic Review
    REVIEW Efficacy of treatments for patients with obsessive-compulsive disorder: A systematic review Yun-Jung Choi, PhD, RN, PMHNP (Lecturer) Keywords Abstract Systematic review; obsessive-compulsive disorder; efficacy of medication. Purpose: This systematic review examines the efficacy of pharmacological therapy for obsessive-compulsive disorder (OCD), addressing two major issues: Correspondence which treatment is most effective in treating the patient’s symptoms and which Yun-Jung Choi, PhD, RN, PMHNP, Red Cross is beneficial for maintaining remission. College of Nursing, 98 Saemoonan-Gil, Data sources: Seven databases were used to acquire articles. The key words Jongno-Gu, Seoul 110-102, Korea; used to search for the relative topics published from 1996 to 2007 were Tel: +82-2-3700-3676; fax: +82-2-3700-3400; ‘‘obsessive-compulsive disorder’’ and ‘‘Yale-Brown obsession-compulsion E-mail: [email protected] scale.’’ Based on the inclusion and exclusion criteria, 25 studies were selected Received: August 2007; from 57 potentially relevant studies. accepted: March 2008 Conclusions: The effects of treatment with clomipramine and selective sero- tonin reuptake inhibitors (SSRIs: fluvoxamine, sertraline, fluoxetine, citalo- doi:10.1111/j.1745-7599.2009.00408.x pram, and escitalopram) proved to be similar, except for the lower adherence rate in case of clomipramine because of its side effects. An adequate drug trial involves administering an effective daily dose for a minimum of 8 weeks. An augmentation strategy proven effective for individuals refractory to monother- apy with SSRI treatment alone is the use of atypical antipsychotics (risperidone, olanzapine, and quetiapine). Implications for practice: Administration of fluvoxamine or sertraline to patients for an adequate duration is recommended as the first-line prescription for OCD, and augmentation therapy with risperidone, olanzapine, or quetiapine is recommended for refractory OCD.
    [Show full text]
  • Antinociceptive Effects of Monoamine Reuptake Inhibitors in Assays of Pain-Stimulated and Pain-Depressed Behaviors
    Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2012 Antinociceptive Effects of Monoamine Reuptake Inhibitors in Assays of Pain-Stimulated and Pain-Depressed Behaviors Marisa Rosenberg Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Medical Pharmacology Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2715 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. ANTINOCICEPTIVE EFFECTS OF MONOAMINE REUPTAKE INHIBITORS IN ASSAYS OF PAIN-STIMULATED AND PAIN-DEPRESSED BEHAVIOR A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University By Marisa B. Rosenberg Bachelor of Science, Temple University, 2008 Advisor: Sidney Stevens Negus, Ph.D. Professor, Department of Pharmacology/Toxicology Virginia Commonwealth University Richmond, VA May, 2012 Acknowledgement First and foremost, I’d like to thank my advisor Dr. Steven Negus, whose unwavering support, guidance and patience throughout my graduate career has helped me become the scientist I am today. His dedication to education, learning and the scientific process has instilled in me a quest for knowledge that I will continue to pursue in life. His thoroughness, attention to detail and understanding of pharmacology has been exemplary to a young person like me just starting out in the field of science. I’d also like to thank all of my committee members (Drs.
    [Show full text]
  • Cipramil® 20 Mg Film-Coated Tablets
    NEW ZEALAND DATA SHEET 1 NAME OF THE MEDICINE Cipramil® 20 mg Film-coated Tablets 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Cipramil 20 mg Film-coated tablets contain 24.98 mg citalopram hydrobromide, corresponding to 20 mg citalopram base. Excipients with known effect: lactose For the full list of excipients, see Section 6.1 List of excipients. 3 PHARMACEUTICAL FORM Cipramil tablets are oval, white, film-coated tablets, 8 mm × 5.5 mm, marked “C” and “N” symmetrically around the score-line. 4 CLINICAL PARTICULARS 4.1 Therapeutic indications Treatment of depressive illness in the initial phase and as maintenance against potential relapse/ recurrence. 4.2 Dose and method of administration The dose may be taken in the morning or evening without regard for food. As the treatment result in general can be evaluated only after 2-3 weeks’ treatment, a possible dose increase in increments of 10 mg should take place with intervals of 2-3 weeks. Adults Cipramil should be administered as a single oral dose of 20 mg daily. Dependent on individual patient response and severity of depression the dose may be increased to a maximum of 40 mg daily. The maximum daily dose should not be exceeded as doses above 40mg/day are associated with an increased risk of QT prolongation. Elderly patients The starting dose is 10mg/day. The dose can be increased by 10mg to a maximum of 20mg/day. Use in children and adolescents (under 18 years of age) Safety and efficacy have not been established in this population. Consequently, citalopram should not be used in children and adolescents under 18 years of age (see Section 4.4 Special warnings and precautions or use).
    [Show full text]
  • Drug Class Review on Second Generation Antidepressants
    Drug Class Review on Second Generation Antidepressants FINAL REPORT November 2004 The Agency for Healthcare Research and Quality has not yet seen or approved this report Gerald Gartlehner, M.D., M.P.H. Richard A. Hansen, Ph.D. Leila Kahwati, M.D., M.P.H. Kathleen N. Lohr, Ph.D. Bradley Gaynes, M.D., M.P.H Tim Carey, M.D., M.P.H. Produced by RTI-UNC Evidence-based Practice Center Cecil G. Sheps Center for Health Services Research University of North Carolina at Chapel Hill 725 Airport Road, CB# 7590 Chapel Hill, NC 27599-7590 Tim Carey, M.D., M.P.H., Director Final Report Drug Effectiveness Review Project Table of Contents Introduction........................................................................................................................ 4 Overview................................................................................................................. 4 Scope and Key Questions ....................................................................................... 7 Methods............................................................................................................................. 10 Literature Search................................................................................................... 10 Study Selection ..................................................................................................... 10 Data Abstraction ................................................................................................... 12 Quality Assessment..............................................................................................
    [Show full text]
  • Emerging Drug List CANADIAN COORDINATING OFFICE for HEALTH ESCITALOPRAM TECHNOLOGY ASSESSMENT
    Emerging Drug List CANADIAN COORDINATING OFFICE FOR HEALTH ESCITALOPRAM TECHNOLOGY ASSESSMENT NO. 35 JANUARY 2003 Generic (Trade Name): Escitalopram (LexaproTM) Manufacturer: Forest Laboratories, Inc. Indication: For the treatment of major depressive disorders in adults.1 Current Regulatory Escitalopram was approved by the US FDA for the above indication in August 2002.2 It Status: was just recently launched in the US, according to the company's web site.3 It was launched in June 2002 in the UK under the trade name Cipralex by Lundbeck for both the treatment of depression and panic disorder.4 In Canada, escitalopram has been sub- mitted for review; no planned marketing date is available (Drug Information, Lundbeck Canada, Montreal: personal communication, 2002 Sep 30). Description: Escitalopram is the S(+) enantiomer of the chiral compound citalopram. It is a selective serotonin reuptake inhibitor that exerts activity in both depressive and anxiety disorders. After oral administration of a single dose, maximal concentrations are reached within three to four hours. It is extensively metabolized via the liver, with eight percent excreted unchanged by the kidneys. After a 20 mg dose, the elimination half-life (of the parent compound) ranges from 22 to 27 hours.5 Current Treatment: Options for the treatment of depressive disorders are vast and include selective serotonin norepinephrine reuptake inhibitors (SNRI), norepinephrine dopamine reuptake inhibitors (NDRI), serotonin-2 antagonists/reuptake inhibitors (SARI), noradrenergic/specific
    [Show full text]
  • TAYSIDE PRESCRIBER Issue No
    TAYSIDE PRESCRIBER Issue No. 122 – May 2012 Produced by the NS Tayside Medicines Governance Unit in conjunction with Mental Health Citalopram & escitalopram:QT interval prolongation New maximum daily dose restrictions, contraindications, and warnings Information has been issued via Drug Safety Update, Volume 5, Issue 5, December 2011 and ‘Dear Healthcare Professional Letters’ for both citalopram and escitalopram regarding new restrictions on the maximum daily doses, contraindications, and warnings. This is as a result of an assessment of a QT study that revealed dose-dependent increase in the QT interval observed with ECG monitoring for both citalopram and escitalopram. Maximum licensed daily doses for citalopram and escitalopram Adults Adults > 65 years Adults with hepatic impairment Citalopram 40 mg 20 mg 20 mg Escitalopram (non-formulary) 20 mg 10 mg 10mg The guidance in NHS Tayside is: ⇒ to review all patients on high dose* citalopram or escitalopram with aim of reducing to new maximum licensed doses ( * above new maximum licensed daily doses as stated in the table above) ⇒ not to prescribe citalopram or escitalopram with other medication known to prolong the QT interval ⇒ not to prescribe citalopram and escitalopram in patients with known QT prolongation or congenital long QT syndrome ⇒ to consider alternative antidepressant in patients with cardiac disease ( e.g. patients with significant bradycardia; recent myocardial infarction or decompensated heart failure) See flow diagram on page 3 for further guidance and table below on medicines known to prolong the QT interval. Medicines known to increase plasma levels of citalopram or escitalopram, e.g. omeprazole & some antivirals may require dose reduction of citalopram or escitalopram and should be used with caution.
    [Show full text]
  • Antidepressants for Functional Gastrointestinal Disorders
    Antidepressants for the treatment of Functional Gastrointestinal Disorders Commonly IBS, constipation, diarrhea, functional abdominal pain and esophageal hypersensitivity Document adapted from literature available from the UNC Center for Functional GI & Motility Disorders What are Functional Gastrointestinal Disorders (FGIDs)? There are many different FGIDs (over 20), but among them, IBS is the most common. FGIDs are characterized by abnormal changes in the movement of muscles throughout the intestines (motility abnormality), an increase in the sensations produced by digestive tract activity (visceral hypersensitivity), and brain-gut dysfunction, especially in the brain’s ability to regulate painful signals from the GI tract. People with IBS have an increased awareness and interpretation of these activities as being abnormal. Motility Abnormality Visceral Hypersensitivity Brain-Gut Dysfunction Instead of normal muscular People with IBS, and other When nerve impulses from the gut reach activity (motility) during digestion, FGIDs, may experience an the brain, they may be experienced as people with IBS may experience increased sensitivity in the more severe or less severe based on the painful spasms and cramping. If nerves of the GI tract. This can regulatory activity of the brain-gut axis. motility is too fast it may produce happen after a GI infection or Signals of pain or discomfort travel from diarrhea and if it is too slow it operation which causes injury the intestines back to the brain. The may result in constipation. Motility to the nerves. This produces a brain usually has the ability to “turn abnormalities may be associated lower pain threshold for normal down” the pain by sending signals that with: cramping, belching, digestive sensations, leading to block nerve impulses produced in the GI urgency, and abdominal pain and discomfort.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,893,053 B2 Seed Et Al
    US0078.93053B2 (12) United States Patent (10) Patent No.: US 7,893,053 B2 Seed et al. (45) Date of Patent: Feb. 22, 2011 (54) TREATING PSYCHOLOGICAL CONDITIONS WO WO 2006/127418 11, 2006 USING MUSCARINIC RECEPTORM ANTAGONSTS (75) Inventors: Brian Seed, Boston, MA (US); Jordan OTHER PUBLICATIONS Mechanic, Sunnyvale, CA (US) Chau et al. (Nucleus accumbens muscarinic receptors in the control of behavioral depression : Antidepressant-like effects of local M1 (73) Assignee: Theracos, Inc., Sunnyvale, CA (US) antagonist in the porSolt Swim test Neuroscience vol. 104, No. 3, pp. 791-798, 2001).* (*) Notice: Subject to any disclaimer, the term of this Lind et al. (Muscarinic acetylcholine receptor antagonists inhibit patent is extended or adjusted under 35 chick Scleral chondrocytes Investigative Ophthalmology & Visual U.S.C. 154(b) by 726 days. Science, vol.39, 2217-2231.* Chau D., et al., “Nucleus Accumbens Muscarinic Receptors in the (21) Appl. No.: 11/763,145 Control of Behavioral Depression: Antidepressant-like Effects of Local M1 Antagonists in the Porsolt Swin Test.” Neuroscience, vol. (22) Filed: Jun. 14, 2007 104, No. 3, Jun. 14, 2001, pp. 791-798. Bechtel, W.D., et al., “Biochemical pharmacology of pirenzepine. (65) Prior Publication Data Similarities with tricyclic antidepressants in antimuscarinic effects only.” Arzneimittelforschung, vol. 36(5), pp. 793-796 (May 1986). US 2007/O293480 A1 Dec. 20, 2007 Chau, D.T. et al., “Nucleus accumbens muscarinic receptors in the control of behavioral depression: antidepressant-like effects of local Related U.S. Application Data Mantagonist in the Porsolt Swim test.” Neuroscience, vol. 104(3), (60) Provisional application No.
    [Show full text]
  • Arrhythmias Caused by Ondansetron: Case Report
    CorSalud 2019 Apr-Jun;11(2):171-174 Cuban Society of Cardiology ________________________ Case Report Arrhythmias caused by ondansetron: Case report Juan M. Chala Tandrón1, MD; Liset Jiménez Fernández2, MD, MSc; Zoila Armada Esmores2, MD, MSc; Yudileidy Brito Ferrer2, MD, MSc; Melba Zayas González2, MD, MSc; and Maiyen García Arcia2, MD 1 Department of Anesthesiology and Resuscitation, Hospital Oncológico Universitario “Dr. Celestino Hernández Robau”. Santa Clara, Villa Clara, Cuba. 2 Department of Pharmacology, Universidad de Ciencias Médicas de Villa Clara. Santa Clara, Villa Clara, Cuba, Cuba. Este artículo también está disponible en español ARTICLE INFORMATION ABSTRACT The ondansetron is used to prevent nausea and vomiting caused by chemothera- Received: April 4, 2019 py, radiotherapy and surgery, belonging to the serotonin 5-HT3 receptor antago- Accepted: May 21, 2019 nists, a natural substance that can cause nausea and vomiting, and it blocks its action. The ondansetron is packaged in the form of rapid disintegration tablets, as Competing interests a solution to be taken orally and in ampules, for parenteral use. The case of a 67- The authors declare no competing year-old female patient is presented, with a diagnosis of breast carcinoma, who interests underwent radical mastectomy with axillary dissection was performed, and who received chemotherapy with adriamycin, cyclophosphamide and paclitaxel; as well as ondansetron to treat nausea and vomiting. The patient presented a wide QRS complex tachycardia after taking the drug. Keywords: Ondansetron, Cardiac arrhythmias, Wide QRS complex tachycardia Arritmias provocadas por ondansetrón: Presentación de un caso RESUMEN El ondansetrón se usa para prevenir las náuseas y los vómitos causados por la quimioterapia, radioterapia y cirugías, pertenece a los antagonistas de receptores de serotonina 5-HT3, una sustancia natural que puede causar náuseas y vómitos, y bloquea su acción.
    [Show full text]
  • Impact of Citalopram and Fluvoxamine on Platelet Response To
    S24_5 Impact of Citalopram and Fluvoxamine on Platelet Response to Clopidogrel, a Randomized, Double-blind, Crossover Trial Bruria Hirsh Racch1, Galia Spectre2, Ella Shai2, Amit Ritter3, David Varon2, Ronny Alcalai3 1School of Pharmacy, Hadassah Hebrew University Medical Center, Israel 2Coagulation Unit, Hematology, Hadassah Hebrew University Medical Center, Israel 3Heart Institute, Hadassah Hebrew University Medical Center, Israel Background: Selective serotonin reuptake inhibitors (SSRI) are widely used antidepressant agents. Studies have shown that use of SSRI in combination with aspirin or warfarin is associated with an increased risk bleeding, while little information is known about the interaction of SSRIs and clopidogrel. Fluvoxamine and citalopram are both SSRIs and while fluvoxamine is an inhibitor of CYP2C19 and thus might reduce the efficacy of clopidogrel, the effect of citalopram on liver metabolism is unknown. Aim: The aim was to assess the effect these two different SSRIs on platelet aggregation and on the laboratory response to clopidogrel. Methods: A randomized, double-blind, crossover study in 15 healthy volunteers comparing the antiplatelet effect of clopidogrel with and without fluvoxamine or citalopram .The response to clopidogrel was assessed by Light Transmittance Aggregometry with10µmol/L ADP and by vasodilator-stimulated phosphoprotein (VASP) phosphorylation, a measure of P2Y12 receptor reactivity. Results: Mean baseline platelet aggregation was 80.1%±3.4 and reduced to 23.5% after treatment with clopidogrel. Both fluvoxamine and citalopram had modest effect on platelet reactivity (65.8%±6.4, p=0.06 vs. baseline and 67.3%±6.3, p=0.07 vs. baseline respectively). Laboratory response to clopidogrel was significantly better in the presence of citalopram as compared to fluvoxamine both in aggregometry (23.4%±3 vs.
    [Show full text]
  • Adverse Effects of First-Line Pharmacologic Treatments of Major Depression in Older Adults
    Draft Comparative Effectiveness Review Number xx Adverse Effects of First-line Pharmacologic Treatments of Major Depression in Older Adults Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 5600 Fishers Lane Rockville, MD 20857 www.ahrq.gov This information is distributed solely for the purposes of predissemination peer review. It has not been formally disseminated by the Agency for Healthcare Research and Quality. The findings are subject to change based on the literature identified in the interim and peer-review/public comments and should not be referenced as definitive. It does not represent and should not be construed to represent an Agency for Healthcare Research and Quality or Department of Health and Human Services (AHRQ) determination or policy. Contract No. 290-2015-00012I Prepared by: Will be included in the final report Investigators: Will be included in the final report AHRQ Publication No. xx-EHCxxx <Month, Year> ii Purpose of the Review To assess adverse events of first-line antidepressants in the treatment of major depressive disorder in adults 65 years or older. Key Messages • Acute treatment (<12 weeks) with o Serotonin norepinephrine reuptake inhibitors (SNRIs) (duloxetine, venlafaxine), but not selective serotonin reuptake inhibitors (SSRIs) (escitalopram, fluoxetine) led to a greater number of adverse events compared with placebo. o SSRIs (citalopram, escitalopram and fluoxetine) and SNRIs (duloxetine and venlafaxine) led to a greater number of patients withdrawing from studies due to adverse events compared with placebo o Details of the contributing adverse events in RCTs were rarely reported to more clearly characterize what adverse events to expect.
    [Show full text]
  • Acute Inhibitory Effects of Antidepressants on Lacrimal Gland Secretion in the Anesthetized Rat
    Physiology and Pharmacology Acute Inhibitory Effects of Antidepressants on Lacrimal Gland Secretion in the Anesthetized Rat Martin Dankis, Ozgu Aydogdu, Gunnar Tobin, and Michael Winder Department of Pharmacology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Correspondence: Michael Winder, PURPOSE. Patients that medicate with antidepressants commonly report dryness of eyes. Department of Pharmacology, The cause is often attributed to the anticholinergic properties of the drugs. However, regu- Institute of Neuroscience and lation of tear production includes a substantial reflex-evoked component and is regulated Physiology, the Sahlgrenska via distinct centers in the brain. Further, the anticholinergic component varies greatly Academy, University of Gothenburg, among antidepressants with different mechanisms of action. In the current study it was Medicinaregatan 13 413 90, Gothenburg, Sweden; wondered if acute administration of antidepressants can disturb production of tears by [email protected]. affecting the afferent and/or central pathway. Received: November 9, 2020 METHODS. Tear production was examined in vivo in anesthetized rats in the presence Accepted: May 10, 2021 or absence of the tricyclic antidepressant (TCA) clomipramine or the selective sero- Published: June 7, 2021 tonin reuptake inhibitor (SSRI) escitalopram. The reflex-evoked production of tears was Citation: Dankis M, Aydogdu O, measured by challenging the surface of the eye with menthol (0.1 mM) and choliner- Tobin G, Winder M. Acute inhibitory gic regulation was examined by intravenous injection with the nonselective muscarinic effects of antidepressants on agonist methacholine (1–5 μg/kg). lacrimal gland secretion in the RESULTS. Acute administration of clomipramine significantly attenuated both reflex- anesthetized rat.
    [Show full text]