Portal de Periódicos da CAPES

Fluoxetine and norfluoxetine plasma concentrations in major depression: a multicenter study

1997; American Psychiatric Association; Volume: 154; Issue: 7 Linguagem: Inglês

10.1176/ajp.154.7.963

1535-7228

Jay D. Amsterdam, Jan Fawcett, F M Quitkin, Fred Reimherr, Jerrold F. Rosenbaum, David Michelson, Mady Hornig, Charles M. Beasley,

Functional Brain Connectivity Studies

Back to table of contents Previous article Next article Full AccessFluoxetine and norfluoxetine plasma concentrations in major depression: a multicenter studyPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.154.7.963AboutSectionsView articleAbstractPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View articleAbstractOBJECTIVE: Prior studies examining the relationship between fluoxetine plasma concentrations and response in major depression have either found no relationship between plasma concentration and response or suggested a curvilinear relationship with a therapeutic window. To elucidate this relationship, plasma concentrations of fluoxetine, norfluoxetine, fluoxetine plus norfluoxetine, and fluoxetine/norfluoxetine ratio were compared to therapeutic response. METHOD: A total of 839 patients (577 women, 262 men; mean age = 40 [SD = 11] with a DSM-III-R diagnosis of major affective disorder who were in the course of either depression or bipolar disorder not otherwise specified and had a minimum baseline score of 16 on the 17-item Hamilton Depression Rating Scale were initially treated. Response was defined as follows: 1) nonresponders had less that a 50% or more reduction from baseline Hamilton depression score, 2) nonremitting responders had a 50% or more reduction from baseline Hamilton depression score but a final score higher than 7, and 3) remitters had a final Hamilton Depression score of 7 or lower. Plasma fluoxetine and norfluoxetine concentrations were measured after 8 weeks of fixed-dose treatment of 20 mg/day. RESULTS: Plasma concentration data were available from 615 patients. Plasma concentration were similar in responders, both remitting and nonremitting (N = 411), and nonresponders (N = 204) for fluoxetine concentrations, for norfluoxetine concentrations, as well as for the sum of fluoxetine and norfluoxetine and for the ratio of fluoxetine to norfluoxetine. No apparent relationship was observed between plasma drug concentration and clinical response. CONCLUSION: Plasma concentrations of fluoxetine and norfluoxetine do not appear to be related to clinical outcome and should not be used to make treatment decisions. FiguresReferencesCited byDetailsCited ByFluoxetine Treatment Decreases Cardiac Vagal Input and Alters the Serotonergic Modulation of the Parasympathetic Outflow in Diabetic Rats20 May 2022 | International Journal of Molecular Sciences, Vol. 23, No. 10Extractable organofluorine analysis: A way to screen for elevated per- and polyfluoroalkyl substance contamination in humans?Environment International, Vol. 159Effects of the Selective Serotonin Reuptake Inhibitor Fluoxetine on Developing Neural Circuits in a Model of the Human Fetal Cortex28 September 2021 | International Journal of Molecular Sciences, Vol. 22, No. 19Vascular sympathetic neurotransmission and its serotonergic regulation are modified by chronic fluoxetine treatmentJournal of Pharmacological Sciences, Vol. 147, No. 1Lysophosphatidic acid-induced pro-thrombotic phosphatidylserine exposure and ionophore-induced microvesiculation is mediated by the scramblase TMEM16F in erythrocytesBlood Cells, Molecules, and Diseases, Vol. 83Behavioral Therapy and Fluoxetine Treatment in Aggressive Dogs: A Case Study11 May 2020 | Animals, Vol. 10, No. 5Fluoxetine Induces Apoptotic and Oxidative Neuronal Death Associated with The Influx of Copper Ions in Cultured Neuronal CellsChonnam Medical Journal, Vol. 56, No. 1Slow-release delivery enhances the pharmacological properties of oral 5-hydroxytryptophan: mouse proof-of-concept29 April 2019 | Neuropsychopharmacology, Vol. 44, No. 12An experimental test of the ovulatory homolog model of female orgasm30 September 2019 | Proceedings of the National Academy of Sciences, Vol. 116, No. 41Fluoxetine Inhibits Enterovirus Replication by Targeting the Viral 2C Protein in a Stereospecific Manner15 July 2019 | ACS Infectious Diseases, Vol. 5, No. 9Fluoxetine oral treatment discloses 5-HT 1D receptor as vagoinhibitor of the cardiac cholinergic neurotransmission in ratCanadian Journal of Physiology and Pharmacology, Vol. 97, No. 2Frontiers in Behavioral Neuroscience, Vol. 13Effects of waterborne exposure to the antidepressant fluoxetine on swimming, shoaling and anxiety behaviours of the mosquitofish Gambusia holbrookiEcotoxicology and Environmental Safety, Vol. 163, Vol. 250International Journal of Neuropsychopharmacology, Vol. 21, No. 1Toxicological Sciences, Vol. 165, No. 2Uptake and Metabolism of Human Pharmaceuticals by Fish: A Case Study with the Opioid Analgesic Tramadol19 October 2017 | Environmental Science & Technology, Vol. 51, No. 21Chemosphere, Vol. 175Personalizing supportive care in oncology patients using pharmacogenetic-driven treatment pathwaysPharmacogenomics, Vol. 17, No. 4Human Psychopharmacology: Clinical and Experimental, Vol. 31, No. 5Clinics in Laboratory Medicine, Vol. 36, No. 4Annals of General Psychiatry, Vol. 15, No. 1The Korean Journal of Physiology & Pharmacology, Vol. 20, No. 4Experimental Neurology, Vol. 270Plasma Fluoxetine Concentrations and Clinical Improvement in an Adolescent Sample Diagnosed With Major Depressive Disorder, Obsessive-Compulsive Disorder, or Generalized Anxiety DisorderJournal of Clinical Psychopharmacology, Vol. 34, No. 3Fluoxetine Administered to Juvenile Monkeys: Effects on the Serotonin Transporter and BehaviorStal Saurav Shrestha, B.A., Eric E. Nelson, Ph.D., Jeih-San Liow, Ph.D., Robert Gladding, B.S., Chul Hyoung Lyoo, M.D., Ph.D., Pam L. Noble, M.S., Cheryl Morse, M.S., Ioline D. Henter, M.A., Jeremy Kruger, B.S., Bo Zhang, Ph.D., Stephen J. Suomi, Ph.D., Per Svenningsson, M.D., Ph.D., Victor W. Pike, Ph.D., James T. Winslow, Ph.D., Ellen Leibenluft, M.D., Daniel S. Pine, M.D., and Robert B. Innis, M.D., Ph.D.1 March 2014 | American Journal of Psychiatry, Vol. 171, No. 3Clinical Pharmacokinetics, Vol. 53, No. 12Journal of Affective Disorders, Vol. 161Journal of Psychiatric Research, Vol. 50Omega-3 fatty acid deficiency does not alter the effects of chronic fluoxetine treatment on central serotonin turnover or behavior in the forced swim test in female ratsPharmacology Biochemistry and Behavior, Vol. 114-115Psychopharmacology, Vol. 221, No. 2PLoS ONE, Vol. 6, No. 1Expert Opinion on Drug Metabolism & Toxicology, Vol. 7, No. 2Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 34, No. 7Neuropsychopharmacology, Vol. 34, No. 10Journal of Constructivist Psychology, Vol. 22, No. 2Journal of Pharmacological Sciences, Vol. 110, No. 1Neuroscience Letters, Vol. 442, No. 1Neuropsychopharmacology, Vol. 33, No. 6Expert Opinion on Drug Metabolism & Toxicology, Vol. 4, No. 12European Neuropsychopharmacology, Vol. 17, No. 9Journal of Chromatography B, Vol. 852, No. 1-2Genetics in Medicine, Vol. 9, No. 12Predictors of Relapse in a Prospective Study of Fluoxetine Treatment of Major DepressionPatrick J. McGrath, M.D.Jonathan W. Stewart, M.D.Frederic M. Quitkin, M.D.Ying Chen, M.D., M.S.Jonathan E. Alpert, M.D., Ph.D.Andrew A. Nierenberg, M.D.Maurizio Fava, M.D.Jianfeng Cheng, M.D., Ph.D.Eva Petkova, Ph.D.1 September 2006 | American Journal of Psychiatry, Vol. 163, No. 9Relevance of assessing drug concentration exposure in pharmacogenetic and imaging studies30 September 2016 | Journal of Psychopharmacology, Vol. 20, No. 4_supplRapid Communications in Mass Spectrometry, Vol. 20, No. 1European Archives of Psychiatry and Clinical Neuroscience, Vol. 256, No. 5Neuropsychopharmacology, Vol. 31, No. 11British Journal of Psychiatry, Vol. 189, No. 4The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants1 April 2022 | Dialogues in Clinical Neuroscience, Vol. 7, No. 3Fluoxetine monotherapy of bipolar type II and bipolar NOS major depression: a double-blind, placebo-substitution, continuation studyInternational Clinical Psychopharmacology, Vol. 20, No. 5Psychopharmacology, Vol. 178, No. 2-3The Journal of Clinical Pharmacology, Vol. 45, No. 10Sex-dependent modulation of treatment response1 April 2022 | Dialogues in Clinical Neuroscience, Vol. 6, No. 1, Vol. 157Pharmacotherapy, Vol. 24, No. 4Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 27, No. 1Journal of Chromatography B, Vol. 783, No. 2The Journal of Clinical Pharmacology, Vol. 43, No. 11Journal of Affective Disorders, Vol. 68, No. 2-3Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 26, No. 5Journal of Clinical Psychopharmacology, Vol. 22, No. 2Therapeutic Drug Monitoring, Vol. 24, No. 5Pharmacotherapy, Vol. 22, No. 8CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages20 December 2001 | Acta Psychiatrica Scandinavica, Vol. 104, No. 3Journal of Clinical Psychopharmacology, Vol. 21, No. 1Journal of Clinical Psychopharmacology, Vol. 21, No. 3Journal of Clinical Psychopharmacology, Vol. 21, No. 6Therapeutic Drug Monitoring, Vol. 23, No. 2Treatment of Bipolar Depression with Twice-Weekly Fluoxetine: Management of Antidepressant-Induced Mania28 June 2016 | Annals of Pharmacotherapy, Vol. 35, No. 1Compliance With Antidepressant Medication in the Treatment of Major Depressive Disorder in Primary Care: A Randomized Comparison of Fluoxetine and a Tricyclic AntidepressantChristopher Thompson, M.D., F.R.C.P., F.R.C.Psych., Robert C. Peveler, D.Phil., F.R.C.Psych., Deborah Stephenson, M.R.C.Psych., A.F.P.M., and Jan McKendrick, B.Sc., M.Sc., C.Stat.1 March 2000 | American Journal of Psychiatry, Vol. 157, No. 3Pharmacology & Therapeutics, Vol. 85, No. 1Therapeutic Drug Monitoring, Vol. 22, No. 2British Journal of Psychiatry, Vol. 176, No. 4Expert Opinion on Pharmacotherapy, Vol. 1, No. 5Adjunctive Lamotrigine Treatment for Major DepressionTHOMAS M. MALTESE, M.D., 1 November 1999 | American Journal of Psychiatry, Vol. 156, No. 11Sublingually Administered Fluoxetine for Major Depression in Medically Compromised PatientsMURAT PAKYUREK, M.D., and ELIAS PASOL, M.D., 1 November 1999 | American Journal of Psychiatry, Vol. 156, No. 11Respiration Physiology, Vol. 115, No. 1Journal of Affective Disorders, Vol. 55, No. 1Journal of Clinical Psychopharmacology, Vol. 19, No. 1Journal of Clinical Psychopharmacology, Vol. 19, No. 2Clarithromycin-Induced ManiaAHMED ABOUESH, M.D., and William R. Hobbs, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Violent Behavior Associated With DonepezilW. P. BOUMAN, M.D., and G. PINNER, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Etiology of Borderline Personality DisorderJUDITH P. SALZMAN, ED.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Drs. Zanarini and Frankenburg ReplyMARY C. ZANARINI, ED.D., and FRANCES R. FRANKENBURG, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Science of AddictionAVIEL GOODMAN, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Dr. O'Brien RepliesCHARLES P. O'BRIEN, M.D., PH.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Use of Psychotropic Medications During LactationJAMES G. LONGHURST, M.D., and ERICA WEISS, M.D. , 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Drs. Stowe and Owens ReplyZACHARY N. STOWE, M.D., and MICHAEL J. OWENS, PH.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Association Between Age at Onset of Schizophrenia and Obstetric ComplicationsRAINER T. SCHAUB, M.D., FRIEDEL M. REISCHIES, M.D., and PETER SCHLATTMAN, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Dr. Verdoux and Colleagues ReplyHÉLÈNE VERDOUX, M.D., , JOHN R. GEDDES, M.R.C.PSYCH., NORIYOSHI TAKEI, M.D., PH.D., and ROBIN M. MURRAY, D.SC., F.R.C.PSYCH., F.R.C.P., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Treatment of Borderline Personality DisorderEDWARD R. SHAPIRO, M.D., and ERIC M. PLAKUN, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Drs. Sharfstein and Quaytman ReplySTEVEN S. SHARFSTEIN, M.D., and MILES S. QUAYTMAN, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Use of Herbal Products and Symptoms of Bipolar DisorderNARESH P. EMMANUEL, M.D., CATHIE JONES, B.A., and R. BRUCE LYDIARD, PH.D., M.D. , 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Antidepressants in Depressed Patients With Irritable Bowel SyndromeIRINA EFREMOVA, M.D., and GREGORY ASNIS, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Response of the Parkinsonian Symptoms of Multiple System Atrophy to ECTW. MICHAEL HOOTEN, M.D., GABRIELLE MELIN, M.D., and JARRETT W. RICHARDSON, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Cocaine and CatatoniaJAY A. GINGRICH, M.D., PH.D., FRANCES RUDNICK-LEVIN, M.D. , CARLOS ALMEIDA, M.D., LORRAINE INNES, M.D., and HOLLY SCHNEIER, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Sertraline in the Treatment of Clozapine-Induced Obsessive-Compulsive BehaviorM. SADIQUR RAHMAN, M.D., JEFFERY J. GRACE, M.D., MICHELE T. PATO, M.D., and BARBARA PRIEST, R.N., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Catatonia Treated With Transcranial Magnetic StimulationNIMROD GRISARU, M.D., BELLA CHUDAKOV, M.D., YURI YAROSLAVSKY, M.D., and R. H. BELMAKER, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Olanzapine Overdose Cause of Acute Extrapyramidal SymptomsR. ANDREW CHAMBERS, M.D., ANNMARIE CARACANSI, M.D., and GORDON WEISS, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Suicide Attempts Among Seropositive Women in New York CityJANE M. SIMONI, PH.D., DAWN K. NERO, M.A., and BETH A. WEINBERG, 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Gabapentin Treatment of Alcohol WithdrawalHUGH MYRICK, M.D., ROBERT MALCOLM, M.D., and KATHLEEN T. BRADY, M.D., PH.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Behavioral Complications Associated With DonepezilSTEVEN P. WENGEL, M.D., , WILLIAM H. ROCCAFORTE, M.D., WILLIAM J. BURKE, M.D., BARBARA L. BAYER, R.N., M.S.N., DENNIS P. MCNEILLY, PSY.D., and DEBRA KNOP, R.N., M.S.N.1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Atypical Neuroleptic Malignant Syndrome and Atypical AntipsychoticsPETER F. BUCKLEY, M.D., and Samia Hasan, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Schizophrenia and Intellectual DeclineJAMES GOLD, PH.D. , 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Letters to the EditorANTHONY DAVID, M.D., M.R.C.PSYCH., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Letters to the EditorJANICE R. STEVENS, M.D. , CARL M. STEVENS, PH.D., , and RICHARD J. WYATT, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Drs. Russell and Murray ReplyAILSA J. RUSSELL, M.SC.CLIN.PSYCH., and ROBIN M. MURRAY, D.SC., F.R.C.PSYCH., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Fluoxetine and NorfluoxetineJEFFREY A. MATTES, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Dr. Amsterdam and Colleagues ReplyJAY D. AMSTERDAM, M.D., , JAN FAWCETT, M.D., FREDERIC M. QUITKIN, M.D., FREDERICK W. REIMHERR, M.D., JERROLD F. ROSENBAUM, M.D., DAVID MICHELSON, M.D., and CHARLES M. BEASLEY, M.D.1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Delirium Following Cessation of Alcohol ConsumptionBRYON ADINOFF, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Letters to the EditorMAX FINK, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Dr. Kranzler and Colleagues ReplyHENRY R. KRANZLER, M.D., , DAVID HERSH, M.D., and ROGER E. MEYER, M.D.1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Risk Factors for Neuroleptic Malignant SyndromeKEITH G. RASMUSSEN, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Letters to the EditorANDREW FRANCIS, PH.D., M.D., SANJAY CHANDRAGIRI, M.D., , and GEORGIOS PETRIDES, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Dr. Sachdev RepliesPERMINDER SACHDEV, M.D., PH.D., F.R.A.N.Z.C.P., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Suicide Risk in SchizophreniaEDUARD VIETA, M.D., EVARISTO NIETO, M.D., and CRISTOBAL GASTO, M.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Dr. Heilä and Colleagues ReplyHANNELE HEILÄ, M.D., MARKUS M. HENRIKSSON, M.D., PH.D., MAURI J. MARTTUNEN, M.D., PH.D., ERKKI T. ISOMETSÄ, M.D., PH.D., MARTTI E. HEIKKINEN, M.D., PH.D., and JOUKO K. LÖNNQVIST, M.D., PH.D., 1 November 1998 | American Journal of Psychiatry, Vol. 155, No. 11Journal of Clinical Psychopharmacology, Vol. 18, No. 6Breast enlargement during chronic antidepressant therapyJournal of Affective Disorders, Vol. 46, No. 2 Volume 154Issue 7 July 1997Pages 963-969 Metrics PDF download History Published online 1 April 2006 Published in print 1 July 1997