Fluvoxamine to Augment Olfactory Recovery For Long COVID-19 Parosmia

Summary

This study will investigate the efficacy of oral fluvoxamine in olfactory improvement following Covid-19- associated parosmia. This is a randomized, double-blinded, placebo-controlled trial.

Timeline

Start

2021-12-14

Primary completion

2022-02-22

Completion

2022-02-22

Publications

• Background Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C, Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, Ris L, Lovato A, De Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020 Aug;277(8):2251-2261. doi: 10.1007/s00405-020-05965-1. Epub 2020 Apr 6.
• Background Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.
• Background Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
• Background Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
• Background Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.
• Background Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
• Background Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.
• Background Jafek BW, Murrow B, Michaels R, Restrepo D, Linschoten M. Biopsies of human olfactory epithelium. Chem Senses. 2002 Sep;27(7):623-8. doi: 10.1093/chemse/27.7.623.
• Background Gudziol V, Buschhuter D, Abolmaali N, Gerber J, Rombaux P, Hummel T. Increasing olfactory bulb volume due to treatment of chronic rhinosinusitis--a longitudinal study. Brain. 2009 Nov;132(Pt 11):3096-101. doi: 10.1093/brain/awp243. Epub 2009 Sep 22.
• Background Schwob JE. Neural regeneration and the peripheral olfactory system. Anat Rec. 2002 Feb 15;269(1):33-49. doi: 10.1002/ar.10047.
• Background Brann JH, Firestein SJ. A lifetime of neurogenesis in the olfactory system. Front Neurosci. 2014 Jun 26;8:182. doi: 10.3389/fnins.2014.00182. eCollection 2014.
• Background Hoffman HJ, Rawal S, Li CM, Duffy VB. New chemosensory component in the U.S. National Health and Nutrition Examination Survey (NHANES): first-year results for measured olfactory dysfunction. Rev Endocr Metab Disord. 2016 Jun;17(2):221-40. doi: 10.1007/s11154-016-9364-1.
• Background Liu B, Luo Z, Pinto JM, Shiroma EJ, Tranah GJ, Wirdefeldt K, Fang F, Harris TB, Chen H. Relationship Between Poor Olfaction and Mortality Among Community-Dwelling Older Adults: A Cohort Study. Ann Intern Med. 2019 May 21;170(10):673-681. doi: 10.7326/M18-0775. Epub 2019 Apr 30.
• Background Pinto JM, Wroblewski KE, Kern DW, Schumm LP, McClintock MK. Olfactory dysfunction predicts 5-year mortality in older adults. PLoS One. 2014 Oct 1;9(10):e107541. doi: 10.1371/journal.pone.0107541. eCollection 2014.
• Background Van Regemorter V, Hummel T, Rosenzweig F, Mouraux A, Rombaux P, Huart C. Mechanisms Linking Olfactory Impairment and Risk of Mortality. Front Neurosci. 2020 Feb 21;14:140. doi: 10.3389/fnins.2020.00140. eCollection 2020.
• Background Soler ZM, Patel ZM, Turner JH, Holbrook EH. A primer on viral-associated olfactory loss in the era of COVID-19. Int Forum Allergy Rhinol. 2020 Jul;10(7):814-820. doi: 10.1002/alr.22578. Epub 2020 Jun 1.
• Background Bitter T, Gudziol H, Burmeister HP, Mentzel HJ, Guntinas-Lichius O, Gaser C. Anosmia leads to a loss of gray matter in cortical brain areas. Chem Senses. 2010 Jun;35(5):407-15. doi: 10.1093/chemse/bjq028. Epub 2010 Mar 15.
• Background Pekala K, Chandra RK, Turner JH. Efficacy of olfactory training in patients with olfactory loss: a systematic review and meta-analysis. Int Forum Allergy Rhinol. 2016 Mar;6(3):299-307. doi: 10.1002/alr.21669. Epub 2015 Dec 1.
• Background Murphy MP, Fishman P, Short SO, Sullivan SD, Yueh B, Weymuller EA Jr. Health care utilization and cost among adults with chronic rhinosinusitis enrolled in a health maintenance organization. Otolaryngol Head Neck Surg. 2002 Nov;127(5):367-76. doi: 10.1067/mhn.2002.129815.
• Background Schiffman SS, Warwick ZS. Flavor enhancement of foods for the elderly can reverse anorexia. Neurobiol Aging. 1988 Jan-Feb;9(1):24-6. doi: 10.1016/s0197-4580(88)80009-5.
• Background Sungnak W, Huang N, Becavin C, Berg M, Queen R, Litvinukova M, Talavera-Lopez C, Maatz H, Reichart D, Sampaziotis F, Worlock KB, Yoshida M, Barnes JL; HCA Lung Biological Network. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020 May;26(5):681-687. doi: 10.1038/s41591-020-0868-6. Epub 2020 Apr 23.
• Background Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM, Oude Munnink BB, de Meulder D, van Amerongen G, van den Brand J, Okba NMA, Schipper D, van Run P, Leijten L, Sikkema R, Verschoor E, Verstrepen B, Bogers W, Langermans J, Drosten C, Fentener van Vlissingen M, Fouchier R, de Swart R, Koopmans M, Haagmans BL. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science. 2020 May 29;368(6494):1012-1015. doi: 10.1126/science.abb7314. Epub 2020 Apr 17.
• Background Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, Yu J, Kang M, Song Y, Xia J, Guo Q, Song T, He J, Yen HL, Peiris M, Wu J. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med. 2020 Mar 19;382(12):1177-1179. doi: 10.1056/NEJMc2001737. Epub 2020 Feb 19. No abstract available.
• Background Meng X, Deng Y, Dai Z, Meng Z. COVID-19 and anosmia: A review based on up-to-date knowledge. Am J Otolaryngol. 2020 Sep-Oct;41(5):102581. doi: 10.1016/j.amjoto.2020.102581. Epub 2020 Jun 2.
• Background Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci. 2020 Apr 1;11(7):995-998. doi: 10.1021/acschemneuro.0c00122. Epub 2020 Mar 13.
• Background Brann DH, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K, Gong B, Chance R, Macaulay IC, Chou HJ, Fletcher RB, Das D, Street K, de Bezieux HR, Choi YG, Risso D, Dudoit S, Purdom E, Mill J, Hachem RA, Matsunami H, Logan DW, Goldstein BJ, Grubb MS, Ngai J, Datta SR. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci Adv. 2020 Jul 31;6(31):eabc5801. doi: 10.1126/sciadv.abc5801. Epub 2020 Jul 24.
• Background Morbini P, Benazzo M, Verga L, Pagella FG, Mojoli F, Bruno R, Marena C. Ultrastructural Evidence of Direct Viral Damage to the Olfactory Complex in Patients Testing Positive for SARS-CoV-2. JAMA Otolaryngol Head Neck Surg. 2020 Oct 1;146(10):972-973. doi: 10.1001/jamaoto.2020.2366. No abstract available.
• Background Politi LS, Salsano E, Grimaldi M. Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia. JAMA Neurol. 2020 Aug 1;77(8):1028-1029. doi: 10.1001/jamaneurol.2020.2125. No abstract available.
• Background Wilson DA, Best AR, Sullivan RM. Plasticity in the olfactory system: lessons for the neurobiology of memory. Neuroscientist. 2004 Dec;10(6):513-24. doi: 10.1177/1073858404267048.
• Background Kollndorfer K, Kowalczyk K, Hoche E, Mueller CA, Pollak M, Trattnig S, Schopf V. Recovery of olfactory function induces neuroplasticity effects in patients with smell loss. Neural Plast. 2014;2014:140419. doi: 10.1155/2014/140419. Epub 2014 Dec 3.
• Background Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, Rusconi S, Gervasoni C, Ridolfo AL, Rizzardini G, Antinori S, Galli M. Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study. Clin Infect Dis. 2020 Jul 28;71(15):889-890. doi: 10.1093/cid/ciaa330. No abstract available.
• Background Lechien JR, Barillari MR, Jouffe L, Saussez S. Anosmia Is a Key Symptom of COVID-19 Infection and Should Be Used as a Diagnostic Tool. Ear Nose Throat J. 2020 Nov;99(9):577-578. doi: 10.1177/0145561320925191. Epub 2020 May 21.
• Background Moein ST, Hashemian SM, Mansourafshar B, Khorram-Tousi A, Tabarsi P, Doty RL. Smell dysfunction: a biomarker for COVID-19. Int Forum Allergy Rhinol. 2020 Aug;10(8):944-950. doi: 10.1002/alr.22587. Epub 2020 Jun 18.
• Background Spinato G, Fabbris C, Polesel J, Cazzador D, Borsetto D, Hopkins C, Boscolo-Rizzo P. Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection. JAMA. 2020 May 26;323(20):2089-2090. doi: 10.1001/jama.2020.6771.
• Background Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, Ganesh S, Varsavsky T, Cardoso MJ, El-Sayed Moustafa JS, Visconti A, Hysi P, Bowyer RCE, Mangino M, Falchi M, Wolf J, Ourselin S, Chan AT, Steves CJ, Spector TD. Real-time tracking of self-reported symptoms to predict potential COVID-19. Nat Med. 2020 Jul;26(7):1037-1040. doi: 10.1038/s41591-020-0916-2. Epub 2020 May 11.
• Background Boscolo-Rizzo P, Borsetto D, Fabbris C, Spinato G, Frezza D, Menegaldo A, Mularoni F, Gaudioso P, Cazzador D, Marciani S, Frasconi S, Ferraro M, Berro C, Varago C, Nicolai P, Tirelli G, Da Mosto MC, Obholzer R, Rigoli R, Polesel J, Hopkins C. Evolution of Altered Sense of Smell or Taste in Patients With Mildly Symptomatic COVID-19. JAMA Otolaryngol Head Neck Surg. 2020 Aug 1;146(8):729-732. doi: 10.1001/jamaoto.2020.1379.
• Background Hendriks AP. Olfactory dysfunction. Rhinology. 1988 Dec;26(4):229-51.
• Background Reden J, Mueller A, Mueller C, Konstantinidis I, Frasnelli J, Landis BN, Hummel T. Recovery of olfactory function following closed head injury or infections of the upper respiratory tract. Arch Otolaryngol Head Neck Surg. 2006 Mar;132(3):265-9. doi: 10.1001/archotol.132.3.265.
• Background Lechien JR, Chiesa-Estomba CM, Beckers E, Mustin V, Ducarme M, Journe F, Marchant A, Jouffe L, Barillari MR, Cammaroto G, Circiu MP, Hans S, Saussez S. Prevalence and 6-month recovery of olfactory dysfunction: a multicentre study of 1363 COVID-19 patients. J Intern Med. 2021 Aug;290(2):451-461. doi: 10.1111/joim.13209. Epub 2021 Jan 5.
• Background Renaud M, Thibault C, Le Normand F, Mcdonald EG, Gallix B, Debry C, Venkatasamy A. Clinical Outcomes for Patients With Anosmia 1 Year After COVID-19 Diagnosis. JAMA Netw Open. 2021 Jun 1;4(6):e2115352. doi: 10.1001/jamanetworkopen.2021.15352.
• Background Whitcroft KL, Hummel T. Olfactory Dysfunction in COVID-19: Diagnosis and Management. JAMA. 2020 Jun 23;323(24):2512-2514. doi: 10.1001/jama.2020.8391. No abstract available.
• Background Rawal S, Hoffman HJ, Bainbridge KE, Huedo-Medina TB, Duffy VB. Prevalence and Risk Factors of Self-Reported Smell and Taste Alterations: Results from the 2011-2012 US National Health and Nutrition Examination Survey (NHANES). Chem Senses. 2016 Jan;41(1):69-76. doi: 10.1093/chemse/bjv057. Epub 2015 Oct 20.
• Background Reden J, Maroldt H, Fritz A, Zahnert T, Hummel T. A study on the prognostic significance of qualitative olfactory dysfunction. Eur Arch Otorhinolaryngol. 2007 Feb;264(2):139-44. doi: 10.1007/s00405-006-0157-0. Epub 2006 Sep 28.
• Background Graziadei PP, Levine RR, Monti Graziadei GA. Plasticity of connections of the olfactory sensory neuron: regeneration into the forebrain following bulbectomy in the neonatal mouse. Neuroscience. 1979;4(6):713-27. doi: 10.1016/0306-4522(79)90002-2. No abstract available.
• Background Seiden AM, Duncan HJ. The diagnosis of a conductive olfactory loss. Laryngoscope. 2001 Jan;111(1):9-14. doi: 10.1097/00005537-200101000-00002.
• Background Saniasiaya J, Narayanan P. Parosmia post COVID-19: an unpleasant manifestation of long COVID syndrome. Postgrad Med J. 2021 Mar 31:postgradmedj-2021-139855. doi: 10.1136/postgradmedj-2021-139855. Online ahead of print. No abstract available.
• Background Cavazzana A, Larsson M, Munch M, Hahner A, Hummel T. Postinfectious olfactory loss: A retrospective study on 791 patients. Laryngoscope. 2018 Jan;128(1):10-15. doi: 10.1002/lary.26606. Epub 2017 May 29.
• Background Kim DH, Kim SW, Hwang SH, Kim BG, Kang JM, Cho JH, Park YJ, Kim SW. Prognosis of Olfactory Dysfunction according to Etiology and Timing of Treatment. Otolaryngol Head Neck Surg. 2017 Feb;156(2):371-377. doi: 10.1177/0194599816679952. Epub 2016 Dec 20.
• Background Schriever VA, Merkonidis C, Gupta N, Hummel C, Hummel T. Treatment of smell loss with systemic methylprednisolone. Rhinology. 2012 Sep;50(3):284-9. doi: 10.4193/Rhino.11.207.
• Background Seo BS, Lee HJ, Mo JH, Lee CH, Rhee CS, Kim JW. Treatment of postviral olfactory loss with glucocorticoids, Ginkgo biloba, and mometasone nasal spray. Arch Otolaryngol Head Neck Surg. 2009 Oct;135(10):1000-4. doi: 10.1001/archoto.2009.141.
• Background Blomqvist EH, Lundblad L, Bergstedt H, Stjarne P. Placebo-controlled, randomized, double-blind study evaluating the efficacy of fluticasone propionate nasal spray for the treatment of patients with hyposmia/anosmia. Acta Otolaryngol. 2003 Sep;123(7):862-8. doi: 10.1080/00016480310002140.
• Background Friedman M, Hamilton C, Samuelson CG, Maley A, Wilson MN, Venkatesan TK, Joseph NJ. Dead Sea salt irrigations vs saline irrigations with nasal steroids for symptomatic treatment of chronic rhinosinusitis: a randomized, prospective double-blind study. Int Forum Allergy Rhinol. 2012 May-Jun;2(3):252-7. doi: 10.1002/alr.21003. Epub 2012 Feb 15.
• Background Yan CH, Overdevest JB, Patel ZM. Therapeutic use of steroids in non-chronic rhinosinusitis olfactory dysfunction: a systematic evidence-based review with recommendations. Int Forum Allergy Rhinol. 2019 Feb;9(2):165-176. doi: 10.1002/alr.22240. Epub 2018 Nov 24.
• Background Nguyen TP, Patel ZM. Budesonide irrigation with olfactory training improves outcomes compared with olfactory training alone in patients with olfactory loss. Int Forum Allergy Rhinol. 2018 Sep;8(9):977-981. doi: 10.1002/alr.22140. Epub 2018 Jun 14.
• Background Barnes PJ. Theophylline. Pharmaceuticals (Basel). 2010 Mar 18;3(3):725-747. doi: 10.3390/ph3030725.
• Background Tomita K, Chikumi H, Tokuyasu H, Yajima H, Hitsuda Y, Matsumoto Y, Sasaki T. Functional assay of NF-kappaB translocation into nuclei by laser scanning cytometry: inhibitory effect by dexamethasone or theophylline. Naunyn Schmiedebergs Arch Pharmacol. 1999 Apr;359(4):249-55. doi: 10.1007/pl00005349.
• Background Henkin RI, Schultz M, Minnick-Poppe L. Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study. Arch Otolaryngol Head Neck Surg. 2012 Nov;138(11):1064-70. doi: 10.1001/2013.jamaoto.342.
• Background Moon C, Simpson PJ, Tu Y, Cho H, Ronnett GV. Regulation of intracellular cyclic GMP levels in olfactory sensory neurons. J Neurochem. 2005 Oct;95(1):200-9. doi: 10.1111/j.1471-4159.2005.03356.x.
• Background Pace U, Hanski E, Salomon Y, Lancet D. Odorant-sensitive adenylate cyclase may mediate olfactory reception. Nature. 1985 Jul 18-24;316(6025):255-8. doi: 10.1038/316255a0.
• Background Ronnett GV, Parfitt DJ, Hester LD, Snyder SH. Odorant-sensitive adenylate cyclase: rapid, potent activation and desensitization in primary olfactory neuronal cultures. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2366-9. doi: 10.1073/pnas.88.6.2366.
• Background Anholt RR. Molecular neurobiology of olfaction. Crit Rev Neurobiol. 1993;7(1):1-22.
• Background Neumann S, Bradke F, Tessier-Lavigne M, Basbaum AI. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron. 2002 Jun 13;34(6):885-93. doi: 10.1016/s0896-6273(02)00702-x.
• Background Henkin RI, Velicu I. cAMP and cGMP in nasal mucus: relationships to taste and smell dysfunction, gender and age. Clin Invest Med. 2008;31(2):E71-7. doi: 10.25011/cim.v31i2.3366.
• Background Henkin RI, Velicu I. cAMP and cGMP in nasal mucus related to severity of smell loss in patients with smell dysfunction. Clin Invest Med. 2008;31(2):E78-84. doi: 10.25011/cim.v31i2.3367.
• Background Henkin RI, Velicu I, Schmidt L. An open-label controlled trial of theophylline for treatment of patients with hyposmia. Am J Med Sci. 2009 Jun;337(6):396-406. doi: 10.1097/MAJ.0b013e3181914a97.
• Background Levy LM, Henkin RI, Lin CS, Hutter A, Schellinger D. Increased brain activation in response to odors in patients with hyposmia after theophylline treatment demonstrated by fMRI. J Comput Assist Tomogr. 1998 Sep-Oct;22(5):760-70. doi: 10.1097/00004728-199809000-00019.
• Background Balmer JE, Blomhoff R. Gene expression regulation by retinoic acid. J Lipid Res. 2002 Nov;43(11):1773-808. doi: 10.1194/jlr.r100015-jlr200.
• Background Rawson NE, LaMantia AS. A speculative essay on retinoic acid regulation of neural stem cells in the developing and aging olfactory system. Exp Gerontol. 2007 Jan-Feb;42(1-2):46-53. doi: 10.1016/j.exger.2006.05.021. Epub 2006 Jul 24.
• Background Hummel T, Whitcroft KL, Rueter G, Haehner A. Intranasal vitamin A is beneficial in post-infectious olfactory loss. Eur Arch Otorhinolaryngol. 2017 Jul;274(7):2819-2825. doi: 10.1007/s00405-017-4576-x. Epub 2017 Apr 22.
• Background Carrie I, Abellan Van Kan G, Rolland Y, Gillette-Guyonnet S, Vellas B. PUFA for prevention and treatment of dementia? Curr Pharm Des. 2009;15(36):4173-85. doi: 10.2174/138161209789909764.
• Background Calder PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans. 2017 Oct 15;45(5):1105-1115. doi: 10.1042/BST20160474. Epub 2017 Sep 12.
• Background Gopinath B, Sue CM, Flood VM, Burlutsky G, Mitchell P. Dietary intakes of fats, fish and nuts and olfactory impairment in older adults. Br J Nutr. 2015 Jul;114(2):240-7. doi: 10.1017/S0007114515001257. Epub 2015 Jun 16.
• Background Yan CH, Rathor A, Krook K, Ma Y, Rotella MR, Dodd RL, Hwang PH, Nayak JV, Oyesiku NM, DelGaudio JM, Levy JM, Wise J, Wise SK, Patel ZM. Effect of Omega-3 Supplementation in Patients With Smell Dysfunction Following Endoscopic Sellar and Parasellar Tumor Resection: A Multicenter Prospective Randomized Controlled Trial. Neurosurgery. 2020 Aug 1;87(2):E91-E98. doi: 10.1093/neuros/nyz559.
• Background Rondanelli M, Opizzi A, Faliva M, Mozzoni M, Antoniello N, Cazzola R, Savare R, Cerutti R, Grossi E, Cestaro B. Effects of a diet integration with an oily emulsion of DHA-phospholipids containing melatonin and tryptophan in elderly patients suffering from mild cognitive impairment. Nutr Neurosci. 2012 Mar;15(2):46-54. doi: 10.1179/1476830511Y.0000000032. Epub 2011 Dec 20.
• Background Jiang X, Finucane HK, Schumacher FR, Schmit SL, Tyrer JP, Han Y, Michailidou K, Lesseur C, Kuchenbaecker KB, Dennis J, Conti DV, Casey G, Gaudet MM, Huyghe JR, Albanes D, Aldrich MC, Andrew AS, Andrulis IL, Anton-Culver H, Antoniou AC, Antonenkova NN, Arnold SM, Aronson KJ, Arun BK, Bandera EV, Barkardottir RB, Barnes DR, Batra J, Beckmann MW, Benitez J, Benlloch S, Berchuck A, Berndt SI, Bickeboller H, Bien SA, Blomqvist C, Boccia S, Bogdanova NV, Bojesen SE, Bolla MK, Brauch H, Brenner H, Brenton JD, Brook MN, Brunet J, Brunnstrom H, Buchanan DD, Burwinkel B, Butzow R, Cadoni G, Caldes T, Caligo MA, Campbell I, Campbell PT, Cancel-Tassin G, Cannon-Albright L, Campa D, Caporaso N, Carvalho AL, Chan AT, Chang-Claude J, Chanock SJ, Chen C, Christiani DC, Claes KBM, Claessens F, Clements J, Collee JM, Correa MC, Couch FJ, Cox A, Cunningham JM, Cybulski C, Czene K, Daly MB, deFazio A, Devilee P, Diez O, Gago-Dominguez M, Donovan JL, Dork T, Duell EJ, Dunning AM, Dwek M, Eccles DM, Edlund CK, Edwards DRV, Ellberg C, Evans DG, Fasching PA, Ferris RL, Liloglou T, Figueiredo JC, Fletcher O, Fortner RT, Fostira F, Franceschi S, Friedman E, Gallinger SJ, Ganz PA, Garber J, Garcia-Saenz JA, Gayther SA, Giles GG, Godwin AK, Goldberg MS, Goldgar DE, Goode EL, Goodman MT, Goodman G, Grankvist K, Greene MH, Gronberg H, Gronwald J, Guenel P, Hakansson N, Hall P, Hamann U, Hamdy FC, Hamilton RJ, Hampe J, Haugen A, Heitz F, Herrero R, Hillemanns P, Hoffmeister M, Hogdall E, Hong YC, Hopper JL, Houlston R, Hulick PJ, Hunter DJ, Huntsman DG, Idos G, Imyanitov EN, Ingles SA, Isaacs C, Jakubowska A, James P, Jenkins MA, Johansson M, Johansson M, John EM, Joshi AD, Kaneva R, Karlan BY, Kelemen LE, Kuhl T, Khaw KT, Khusnutdinova E, Kibel AS, Kiemeney LA, Kim J, Kjaer SK, Knight JA, Kogevinas M, Kote-Jarai Z, Koutros S, Kristensen VN, Kupryjanczyk J, Lacko M, Lam S, Lambrechts D, Landi MT, Lazarus P, Le ND, Lee E, Lejbkowicz F, Lenz HJ, Leslie G, Lessel D, Lester J, Levine DA, Li L, Li CI, Lindblom A, Lindor NM, Liu G, Loupakis F, Lubinski J, Maehle L, Maier C, Mannermaa A, Marchand LL, Margolin S, May T, McGuffog L, Meindl A, Middha P, Miller A, Milne RL, MacInnis RJ, Modugno F, Montagna M, Moreno V, Moysich KB, Mucci L, Muir K, Mulligan AM, Nathanson KL, Neal DE, Ness AR, Neuhausen SL, Nevanlinna H, Newcomb PA, Newcomb LF, Nielsen FC, Nikitina-Zake L, Nordestgaard BG, Nussbaum RL, Offit K, Olah E, Olama AAA, Olopade OI, Olshan AF, Olsson H, Osorio A, Pandha H, Park JY, Pashayan N, Parsons MT, Pejovic T, Penney KL, Peters WHM, Phelan CM, Phipps AI, Plaseska-Karanfilska D, Pring M, Prokofyeva D, Radice P, Stefansson K, Ramus SJ, Raskin L, Rennert G, Rennert HS, van Rensburg EJ, Riggan MJ, Risch HA, Risch A, Roobol MJ, Rosenstein BS, Rossing MA, De Ruyck K, Saloustros E, Sandler DP, Sawyer EJ, Schabath MB, Schleutker J, Schmidt MK, Setiawan VW, Shen H, Siegel EM, Sieh W, Singer CF, Slattery ML, Sorensen KD, Southey MC, Spurdle AB, Stanford JL, Stevens VL, Stintzing S, Stone J, Sundfeldt K, Sutphen R, Swerdlow AJ, Tajara EH, Tangen CM, Tardon A, Taylor JA, Teare MD, Teixeira MR, Terry MB, Terry KL, Thibodeau SN, Thomassen M, Bjorge L, Tischkowitz M, Toland AE, Torres D, Townsend PA, Travis RC, Tung N, Tworoger SS, Ulrich CM, Usmani N, Vachon CM, Van Nieuwenhuysen E, Vega A, Aguado-Barrera ME, Wang Q, Webb PM, Weinberg CR, Weinstein S, Weissler MC, Weitzel JN, West CML, White E, Whittemore AS, Wichmann HE, Wiklund F, Winqvist R, Wolk A, Woll P, Woods M, Wu AH, Wu X, Yannoukakos D, Zheng W, Zienolddiny S, Ziogas A, Zorn KK, Lane JM, Saxena R, Thomas D, Hung RJ, Diergaarde B, McKay J, Peters U, Hsu L, Garcia-Closas M, Eeles RA, Chenevix-Trench G, Brennan PJ, Haiman CA, Simard J, Easton DF, Gruber SB, Pharoah PDP, Price AL, Pasaniuc B, Amos CI, Kraft P, Lindstrom S. Shared heritability and functional enrichment across six solid cancers. Nat Commun. 2019 Jan 25;10(1):431. doi: 10.1038/s41467-018-08054-4.
• Background Bourrie B, Bribes E, Derocq JM, Vidal H, Casellas P. Sigma receptor ligands: applications in inflammation and oncology. Curr Opin Investig Drugs. 2004 Nov;5(11):1158-63.
• Background Lewis R, Li J, McCormick PJ, L-H Huang C, Jeevaratnam K. Is the sigma-1 receptor a potential pharmacological target for cardiac pathologies? A systematic review. Int J Cardiol Heart Vasc. 2019 Dec 28;26:100449. doi: 10.1016/j.ijcha.2019.100449. eCollection 2020 Feb.
• Background Oxombre B, Lee-Chang C, Duhamel A, Toussaint M, Giroux M, Donnier-Marechal M, Carato P, Lefranc D, Zephir H, Prin L, Melnyk P, Vermersch P. High-affinity sigma1 protein agonist reduces clinical and pathological signs of experimental autoimmune encephalomyelitis. Br J Pharmacol. 2015 Apr;172(7):1769-82. doi: 10.1111/bph.13037. Epub 2015 Feb 10.
• Background Nishimura T, Ishima T, Iyo M, Hashimoto K. Potentiation of nerve growth factor-induced neurite outgrowth by fluvoxamine: role of sigma-1 receptors, IP3 receptors and cellular signaling pathways. PLoS One. 2008 Jul 2;3(7):e2558. doi: 10.1371/journal.pone.0002558.
• Background Hashimoto K. Sigma-1 receptor chaperone and brain-derived neurotrophic factor: emerging links between cardiovascular disease and depression. Prog Neurobiol. 2013 Jan;100:15-29. doi: 10.1016/j.pneurobio.2012.09.001. Epub 2012 Oct 5.
• Background Ishima T, Fujita Y, Hashimoto K. Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells. Eur J Pharmacol. 2014 Mar 15;727:167-73. doi: 10.1016/j.ejphar.2014.01.064. Epub 2014 Feb 5.
• Background Hashimoto K. Activation of sigma-1 receptor chaperone in the treatment of neuropsychiatric diseases and its clinical implication. J Pharmacol Sci. 2015 Jan;127(1):6-9. doi: 10.1016/j.jphs.2014.11.010. Epub 2014 Dec 4.
• Background Cobos EJ, Entrena JM, Nieto FR, Cendan CM, Del Pozo E. Pharmacology and therapeutic potential of sigma(1) receptor ligands. Curr Neuropharmacol. 2008 Dec;6(4):344-66. doi: 10.2174/157015908787386113.
• Background Hallifax D, Houston JB. Saturable uptake of lipophilic amine drugs into isolated hepatocytes: mechanisms and consequences for quantitative clearance prediction. Drug Metab Dispos. 2007 Aug;35(8):1325-32. doi: 10.1124/dmd.107.015131. Epub 2007 Apr 30.
• Background Sukhatme VP, Reiersen AM, Vayttaden SJ, Sukhatme VV. Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19. Front Pharmacol. 2021 Apr 20;12:652688. doi: 10.3389/fphar.2021.652688. eCollection 2021.
• Background Lenze EJ, Mattar C, Zorumski CF, Stevens A, Schweiger J, Nicol GE, Miller JP, Yang L, Yingling M, Avidan MS, Reiersen AM. Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial. JAMA. 2020 Dec 8;324(22):2292-2300. doi: 10.1001/jama.2020.22760.
• Background Reis G, Dos Santos Moreira-Silva EA, Silva DCM, Thabane L, Milagres AC, Ferreira TS, Dos Santos CVQ, de Souza Campos VH, Nogueira AMR, de Almeida APFG, Callegari ED, de Figueiredo Neto AD, Savassi LCM, Simplicio MIC, Ribeiro LB, Oliveira R, Harari O, Forrest JI, Ruton H, Sprague S, McKay P, Glushchenko AV, Rayner CR, Lenze EJ, Reiersen AM, Guyatt GH, Mills EJ; TOGETHER investigators. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial. Lancet Glob Health. 2022 Jan;10(1):e42-e51. doi: 10.1016/S2214-109X(21)00448-4. Epub 2021 Oct 28.
• Background Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.
• Background Dunlop BW, Gray J, Rapaport MH. Transdiagnostic Clinical Global Impression Scoring for Routine Clinical Settings. Behav Sci (Basel). 2017 Jun 27;7(3):40. doi: 10.3390/bs7030040.
• Background Doty RL, Shaman P, Kimmelman CP, Dann MS. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope. 1984 Feb;94(2 Pt 1):176-8. doi: 10.1288/00005537-198402000-00004.
• Background Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83.
• Background Henry JA. Overdose and safety with fluvoxamine. Int Clin Psychopharmacol. 1991 Dec;6 Suppl 3:41-5; discussion 45-7. doi: 10.1097/00004850-199112003-00004.
• Background Kharasch ED, Neiner A, Kraus K, Blood J, Stevens A, Schweiger J, Miller JP, Lenze EJ. Bioequivalence and Therapeutic Equivalence of Generic and Brand Bupropion in Adults With Major Depression: A Randomized Clinical Trial. Clin Pharmacol Ther. 2019 May;105(5):1164-1174. doi: 10.1002/cpt.1309. Epub 2019 Jan 18.
• Background Lenze EJ, Stevens A, Waring JD, Pham VT, Haddad R, Shimony J, Miller JP, Bowie CR. Augmenting Computerized Cognitive Training With Vortioxetine for Age-Related Cognitive Decline: A Randomized Controlled Trial. Am J Psychiatry. 2020 Jun 1;177(6):548-555. doi: 10.1176/appi.ajp.2019.19050561. Epub 2020 Mar 26.
• Background Christensen M, Tybring G, Mihara K, Yasui-Furokori N, Carrillo JA, Ramos SI, Andersson K, Dahl ML, Bertilsson L. Low daily 10-mg and 20-mg doses of fluvoxamine inhibit the metabolism of both caffeine (cytochrome P4501A2) and omeprazole (cytochrome P4502C19). Clin Pharmacol Ther. 2002 Mar;71(3):141-52. doi: 10.1067/mcp.2002.121788.
• Background Budha NR, Ji T, Musib L, Eppler S, Dresser M, Chen Y, Jin JY. Evaluation of Cytochrome P450 3A4-Mediated Drug-Drug Interaction Potential for Cobimetinib Using Physiologically Based Pharmacokinetic Modeling and Simulation. Clin Pharmacokinet. 2016 Nov;55(11):1435-1445. doi: 10.1007/s40262-016-0412-5.
• Background Vezmar S, Miljkovic B, Vucicevic K, Timotijevic I, Prostran M, Todorovic Z, Pokrajac M. Pharmacokinetics and efficacy of fluvoxamine and amitriptyline in depression. J Pharmacol Sci. 2009 May;110(1):98-104. doi: 10.1254/jphs.09013fp.
• Background Gebara MA, Shea ML, Lipsey KL, Teitelbaum SL, Civitelli R, Muller DJ, Reynolds CF 3rd, Mulsant BH, Lenze EJ. Depression, antidepressants, and bone health in older adults: a systematic review. J Am Geriatr Soc. 2014 Aug;62(8):1434-41. doi: 10.1111/jgs.12945. Epub 2014 Jul 15.
• Background Dixon AE, Kaminsky DA, Holbrook JT, Wise RA, Shade DM, Irvin CG. Allergic rhinitis and sinusitis in asthma: differential effects on symptoms and pulmonary function. Chest. 2006 Aug;130(2):429-35. doi: 10.1378/chest.130.2.429.
• Background Gebara MA, Lipsey KL, Karp JF, Nash MC, Iaboni A, Lenze EJ. Cause or Effect? Selective Serotonin Reuptake Inhibitors and Falls in Older Adults: A Systematic Review. Am J Geriatr Psychiatry. 2015 Oct;23(10):1016-28. doi: 10.1016/j.jagp.2014.11.004. Epub 2014 Nov 25.

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