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{{Short description|Atypical antipsychotic medication}} |
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{{Drugbox| verifiedrevid = 409599789 |
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{{Use dmy dates|date=February 2024}} |
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{{cs1 config|name-list-style=vanc|display-authors=6}} |
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| IUPAC_name = 2-methyl-4-(4-methyl-1-piperazinyl)-10''H''-thienobenzodiazepine |
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{{Infobox drug |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 418858405 |
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| image = Olanzapine.svg |
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| image = Olanzapine.svg |
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| width = 172 |
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| width = 200 |
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| alt = |
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| image2= Olanzapine-from-xtal-3D-balls.png |
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| image2 = Olanzapine-from-xtal-3D-balls.png |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| width2 = 225 |
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| alt2 = <!-- Clinical data --> |
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| pronounce = |
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| tradename = Zyprexa, others<ref name=Drugnames/> |
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| Drugs.com = {{drugs.com|monograph|olanzapine}} |
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| MedlinePlus = a601213 |
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| DailyMedID = Olanzapine |
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| pregnancy_AU = C |
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| pregnancy_AU_comment = |
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| routes_of_administration = ], ] |
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| class = ] |
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| ATC_prefix = N05 |
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| ATC_suffix = AH03 |
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| ATC_supplemental = <!-- Legal status --> |
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| legal_AU = S4 |
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| legal_AU_comment = |
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| legal_BR = C1 |
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| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 – Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 – Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=] |language=pt-BR |publication-date=4 April 2023}}</ref> |
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| legal_CA = Rx-only |
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| legal_CA_comment = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled --> |
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| legal_DE_comment = |
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| legal_NZ = Rx-only |
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| legal_NZ_comment = |
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| legal_UK = POM |
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| legal_UK_comment = <ref name=EMC /> |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Zyprexa FDA label">{{cite web | title=Zyprexa- olanzapine tablet; Zyprexa Zydis- olanzapine tablet, orally disintegrating; Zyprexa intramuscular- olanzapine injection, powder, for solution | website=DailyMed | date=13 December 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5051fbc-846b-4946-82df-341fb1216341 | access-date=17 October 2024}}</ref> |
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| legal_EU = Rx-only |
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| legal_EU_comment = <ref name="Zyprexa EPAR">{{cite web | title=Zyprexa EPAR | website=] (EMA) | date=27 September 1996 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zyprexa | access-date=27 February 2024}}</ref><ref>{{cite web | title=Zypadhera | website=] (EMA) | date=19 November 2008 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zypadhera | access-date=26 October 2024}}</ref> |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = <!-- For countries not listed above --> |
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<!-- Pharmacokinetic data -->| bioavailability = 60–65%<ref>{{cite journal | vauthors = Kassahun K, Mattiuz E, Nyhart E, Obermeyer B, Gillespie T, Murphy A, Goodwin RM, Tupper D, Callaghan JT, Lemberger L | title = Disposition and biotransformation of the antipsychotic agent olanzapine in humans | journal = Drug Metabolism and Disposition | volume = 25 | issue = 1 | pages = 81–93 | date = January 1997 | pmid = 9010634 | url = https://dmd.aspetjournals.org/content/25/1/81.long }}</ref><ref>{{cite journal | vauthors = Callaghan JT, Bergstrom RF, Ptak LR, Beasley CM | title = Olanzapine. Pharmacokinetic and pharmacodynamic profile | journal = Clinical Pharmacokinetics | volume = 37 | issue = 3 | pages = 177–193 | date = September 1999 | pmid = 10511917 | doi = 10.2165/00003088-199937030-00001 }}</ref><ref>{{cite journal | vauthors = Mauri MC, Volonteri LS, Colasanti A, Fiorentini A, De Gaspari IF, Bareggi SR | title = Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response | journal = Clinical Pharmacokinetics | volume = 46 | issue = 5 | pages = 359–388 | date = 2007 | pmid = 17465637 | doi = 10.2165/00003088-200746050-00001 | s2cid = 43859718 }}</ref> |
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| protein_bound = 93%<ref name=TGA/> |
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| metabolism = ] (direct glucuronidation and ] mediated oxidation) |
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| metabolites = |
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| onset = |
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| elimination_half-life = 33 hours, 51.8 hours (elderly)<ref name=TGA/> |
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| duration_of_action = |
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| excretion = Urine (57%; 7% as unchanged drug), faeces (30%)<ref name=TGA/><ref name=MSR/> |
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<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 132539-06-1 |
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| PubChem = 4585 |
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| IUPHAR_ligand = 47 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB00334 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 10442212 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = N7U69T4SZR |
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| UNII = N7U69T4SZR |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D00454 |
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| KEGG = D00454 |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| InChI = 1/C17H20N4S/c1-12-11-13-16(21-9-7-20(2)8-10-21)18-14-5-3-4-6-15(14)19-17(13)22-12/h3-6,11,19H,7-10H2,1-2H3 |
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| ChEBI = 7735 |
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| InChIKey = KVWDHTXUZHCGIO-UHFFFAOYAQ |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 715 |
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| ChEMBL = 715 |
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| NIAID_ChemDB = |
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| PDB_ligand = |
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| synonyms = <!-- Chemical and physical data --> |
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| IUPAC_name = 2-Methyl-4-(4-methyl-1-piperazinyl)-10''H''-thienobenzodiazepine |
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| C = 17 |
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| H = 20 |
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| N = 4 |
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| S = 1 |
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| SMILES = CN1CCN(CC1)C/2=N/c4ccccc4Nc3sc(C)cc\23 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C17H20N4S/c1-12-11-13-16(21-9-7-20(2)8-10-21)18-14-5-3-4-6-15(14)19-17(13)22-12/h3-6,11,19H,7-10H2,1-2H3 |
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| StdInChI = 1S/C17H20N4S/c1-12-11-13-16(21-9-7-20(2)8-10-21)18-14-5-3-4-6-15(14)19-17(13)22-12/h3-6,11,19H,7-10H2,1-2H3 |
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| StdInChI_comment = |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = KVWDHTXUZHCGIO-UHFFFAOYSA-N |
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| StdInChIKey = KVWDHTXUZHCGIO-UHFFFAOYSA-N |
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| density = |
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| CAS_number = 132539-06-1 |
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| density_notes = |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 10442212 |
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| ATC_prefix = N05 |
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| ATC_suffix = AH03 |
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| PubChem = 4585 |
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| IUPHAR_ligand = 47 |
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| DrugBank = DB00334 |
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| C=17|H=20|N=4|S=1 |
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| molecular_weight = 312.439 |
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| melting_point = 195 |
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| melting_point = 195 |
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| melting_high = |
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| melting_notes = |
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| boiling_point = |
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| boiling_notes = |
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| solubility = Practically insoluble in water |
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| solubility = Practically insoluble in water |
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| sol_units = |
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| smiles = CN1CCN(CC1)C/2=N/c4ccccc4Nc3sc(C)cc\23 |
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| specific_rotation = |
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| bioavailability = 87% <ref>{{cite book |
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| last1 = Burton |
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| first1 = Michael E. |
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| last2 = Shaw |
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| first2 = Leslie M. |
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| last3 = Schentag |
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| first3 = Jerome J. |
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| last4 = Evans |
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| first4 = William E. |
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| authorlink = |
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| coauthors = |
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| title = Applied Pharmacokinetics & Pharmacodynamics: Principles of Therapeutic Drug Monitoring |
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| publisher = Lippincott Williams & Wilkins; Fourth Edition edition |
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| date = May 1, 2005 |
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| location = |
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| pages = 815 |
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| url = |
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| doi = |
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| id = |
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| isbn = 978-0781744317}}</ref> |
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| metabolism = Hepatic (direct glucuronidation and CYP mediated oxidation) |
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| elimination_half-life = 21–54 hours |
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| excretion = urine 57%, feces 30% |
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| pregnancy_category = C |
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| legal_status = Rx-only |
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| routes_of_administration = oral, intramuscular |
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}} |
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}} |
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<!-- Definition and medical uses --> |
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'''Olanzapine''' (trade names '''Zyprexa''', '''Zalasta''', '''Zolafren''', '''Olzapin''', '''Oferta''', '''Zypadhera''' or in combination with ] ''']''') is an ], approved by the ] for the treatment of ] and ].<ref name = olanzapinepi> |
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'''Olanzapine''', sold under the brand name '''Zyprexa''' among others, is an ] primarily used to treat ] and ].<ref name=AHFS2018/> It is also sometimes used ] for treatment of ]<ref name="Razvi_2019">{{cite journal | vauthors = Razvi Y, Chan S, McFarlane T, McKenzie E, Zaki P, DeAngelis C, Pidduck W, Bushehri A, Chow E, Jerzak KJ | title = ASCO, NCCN, MASCC/ESMO: a comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in adult patients | journal = Supportive Care in Cancer | volume = 27 | issue = 1 | pages = 87–95 | date = January 2019 | pmid = 30284039 | doi = 10.1007/s00520-018-4464-y }}</ref> and as an ].<ref>{{cite journal | vauthors = Sandhya L, Devi Sreenivasan N, Goenka L, Dubashi B, Kayal S, Solaiappan M, Govindarajalou R, Kt H, Ganesan P | title = Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer | journal = Journal of Clinical Oncology | volume = 41 | issue = 14 | pages = 2617–2627 | date = May 2023 | pmid = 36977285 | doi = 10.1200/JCO.22.01997 }}</ref> For schizophrenia, it can be used for both new-onset disease and long-term maintenance.<ref name=AHFS2018/> It is taken ] or by ].<ref name=AHFS2018/> |
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{{cite web |
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| last = |
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| first = |
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| authorlink = |
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| coauthors = |
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| title = Olanzapine Prescribing Information |
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| work = |
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| publisher = Eli Lilly and Company |
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| date = 2009-03-19 |
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| url = http://pi.lilly.com/us/zyprexa-pi.pdf |
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| format = PDF |
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| doi = |
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| accessdate = 2009-09-06 |
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}}</ref> Olanzapine is structurally similar to ], but is classified as a ]. |
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The olanzapine formulations are manufactured and marketed by the ] ], whose patent for olanzapine proper expires in 2011 (in October 2009 a Canadian judge ruled that the 1991 patent was invalid).<ref></ref> Sales of Zyprexa in 2008 were $2.2B in the US alone, and $4.7B in total.<ref> |
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{{cite web |
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| title = Lilly 2008 Annual Report |
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| publisher = Lilly |
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| year = 2009 |
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| url = http://files.shareholder.com/downloads/LLY/696621960x0x296463/611E167A-61C9-4C03-8866-ACF5FA7C8953/English.PDF |
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|format=PDF |
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| accessdate = 2009-08-06 |
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}} |
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</ref> |
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<!-- Side effects and mechanism --> |
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==Indications and Usage== |
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Common side effects include significant ], ], ], ], ], and ].<ref name="AHFS2018" /> Other side effects include ], ], ], ], ], and ].<ref name=AHFS2018/> In older people with ], its use increases the risk of death.<ref name=AHFS2018/> Use in the later part of ] may result in a ] in the baby for some time after birth.<ref name=AHFS2018/> Although how it works is not entirely clear, it blocks ] and ]s.<ref name=AHFS2018/> |
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*oral formulation: acute and maintenance treatment of schizophrenia in adults, acute treatment of manic or mixed episodes associated with bipolar I disorder (monotherapy and in combination with ] or ]) |
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*intramuscular formulation: acute agitation associated with schizophrenia and bipolar I mania in adults |
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*oral formulation combined with ]: treatment of acute depressive episodes associated with bipolar I disorder in adults, or treatment of acute, resistant depression in adults <ref>treatment resistant depression defined as major depressive disorder in adult patients who do not respond to two separate trials of different antidepressants of adequate dose and duration in the current episode</ref> |
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<!-- History and culture --> |
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Known FDA approvals are as follows: |
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Olanzapine was patented in 1991 and approved for medical use in the ] in 1996.<ref name=AHFS2018>{{cite web |title=Olanzapine, Olanzapine Pamoate Monograph for Professionals |url=https://www.drugs.com/monograph/olanzapine-olanzapine-pamoate.html |website=Drugs.com |publisher=AHFS |access-date=24 December 2018 }}</ref><ref>{{cite book | vauthors = Taylor D, Paton C, Kapur S |title=The Maudsley Prescribing Guidelines in Psychiatry |date=2015 |publisher=Wiley-Blackwell |location=London, U K|isbn=978-1-118-75460-3 |page=16 |edition=12th |url=https://books.google.com/books?id=XvOyBwAAQBAJ&pg=PA16}}</ref> It is available as a ].<ref name=AHFS2018/> In 2022, it was the 171st most commonly prescribed medication in the United States, with more than 3{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Olanzapine Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Olanzapine | access-date = 30 August 2024 }}</ref> It is on the ].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> |
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{{TOC limit}} |
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] also markets olanzapine in a fixed-dose combination with ] as ] (Symbyax), which was approved by the US FDA for the treatment of depressive episodes of ] in 2003 and for ] in 2009.<ref name="Symbyax FDA label">{{cite web | title=Symbyax- olanzapine and fluoxetine hydrochloride capsule | website=DailyMed | date=21 April 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6b28c424-0b7e-4b75-b090-f116b113554e | access-date=30 September 2020}}</ref> |
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*approved for the ''treatment of the manifestations of psychotic disorders'' on September 6, 1996<ref name = "NDA 20-592"> |
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{{cite web |
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| title = NDA 20-592 |
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| publisher = Food and Drug Administration |
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| date = 1996-09-06 |
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| url = http://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf |
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|format=PDF| accessdate = 2009-09-06 |
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}}</ref> |
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] also markets olanzapine in a fixed-dose combination with ] as ] (Lybalvi), which was approved by the US FDA for the treatment of ] and ] in May 2021. Lybalvi suppresses the metabolic side effect of olanzapine by nearly 2%.<ref name="Lybalvi FDA label">{{cite web |title=DailyMed - Lybalvi- olanzapine and samidorphan l-malate tablet, film coated |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=32ffddd1-4e2b-45d9-9b36-bb730167ec80 |website=DailyMed }}</ref> |
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*approved in combination with fluoxetine for the ''treatment of depressive episodes associated with Bipolar disorder'' on December 24, 2003<ref> |
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{{cite web |
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| title = NDA 21-520 |
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| publisher = Food and Drug Administration |
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| date = 2003-12-24 |
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| url = http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2003/21520ltr.pdf |
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|format=PDF| accessdate = 2009-09-06 |
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}}</ref> |
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==Medical uses== |
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*approved for the ''long-term treatment of bipolar I disorder'' on January 14, 2004<ref> |
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It is approved by the FDA for the following indications: |
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{{cite web |
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| title = NDA 20-592 / S-019 |
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| publisher = Food and Drug Administration |
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| date = 2004-01-14 |
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| url = http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/20592se1-019ltr.pdf |
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|format=PDF |
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| accessdate = 2009-09-06 |
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}}</ref> |
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* schizophrenia. |
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*approved in combination with fluoxetine for treatment of resistant depression on March 19, 2009.<ref></ref> |
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* acute treatment of ] or ] associated with ] and maintenance treatment of bipolar I disorder. |
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* adjunct to ] or ] in the treatment of manic or mixed episodes associated with bipolar I disorder. |
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* combination ] for the treatment of depressive episodes associated with bipolar I disorder.<ref>{{cite book | vauthors = Thomas K, Saadabadi A | chapter = Olanzapine |date=2023 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK532903/ | title = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30422498 |access-date=20 November 2022 }}</ref><ref>{{Cite web |title=Olanzapine Indications: FDA-Approved Uses |url=https://psychopharmacologyinstitute.com/publication/olanzapine-indications-fda-approved-uses-2160 |access-date=20 November 2022 |website=psychopharmacologyinstitute.com}}</ref><ref name="Zyprexa FDA label" /> |
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In the United Kingdom and Australia, it is approved for schizophrenia, moderate to severe manic episodes, alone, or in combination with lithium or valproate and the short-term treatment of acute manic episodes associated with bipolar I disorder.<ref name=EMC /><ref>{{Cite web |title=Olanzapine AN Tablets |url=https://www.nps.org.au/medicine-finder/olanzapine-an-tablets |access-date=20 November 2022 |website=NPS MedicineWise |date=May 2018 }}</ref> |
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===Off-label uses=== |
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Case-reports, open-label, and small pilot studies suggest efficacy of olanzapine for the treatment of some anxiety spectrum disorders (e.g. ],<ref>{{cite journal |author=Pollack MH, Simon NM, Zalta AK, Worthington JJ, Hoge EA, Mick E, Kinrys G, Oppenheimer J. |title=Olanzapine augmentation of fluoxetine for refractory generalized anxiety disorder: a placebo controlled study. |journal=Biol Psychiatry. |volume=59 |issue=3 |pages=211–5 |year=2006 | pmid=16139813 |doi=10.1016/j.biopsych.2005.07.005}}</ref> ],<ref>{{cite journal |author=Sepede G, De Berardis D, Gambi F, Campanella D, La Rovere R, D'Amico M, Cicconetti A, Penna L, Peca S, Carano A, Mancini E, Salerno RM, Ferro FM. |title=Olanzapine augmentation in treatment-resistant panic disorder: a 12-week, fixed-dose, open-label trial. |journal=J Clin Psychopharmacol. |volume=107 |issue=5 |pages=394–6 |year=2003 | pmid=16415705 }}</ref> ]);<ref>{{cite journal |author=Jakovljević M, Sagud M, Mihaljević-Peles A. |title=Olanzapine in the treatment-resistant, combat-related PTSD—a series of case reports. |journal=] |volume=26 |issue=1 |pages=45–9 |year=2006 | pmid=12752037 |doi=10.1111/j.1600-0447.1951.tb10961.x }}</ref> however, olanzapine has not been rigorously evaluated in randomized, placebo-controlled trials for this use and is not FDA approved for these indications. Other common off-label uses of olanzapine include the treatment of eating disorders (e.g. ]) and as an adjunctive treatment for major depressive disorder without psychotic features. It has also been used for ] and ].<ref></ref> Olanzapine is also used in many addiction clinics as a sleep aid (usually 2.5–5 mg) due to its low abuse profile and zero addictive properties.<ref>{{cite news | url=http://www.forbes.com/2004/09/08/cx_mh_0908seroquel.html | title=Antiphyscotic used as sleeping pill | id=0028–0836 | accessdate=2005-12-11 | work=Forbes}}</ref> |
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Olanzapine is also used off-label for the treatment of chemotherapy-induced nausea and vomiting.<ref name="Razvi_2019" /> |
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====Prevention of psychosis==== |
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Olanzapine has been considered as part of an ] approach for schizophrenia. The Prevention through Risk Identification, Management, and Education (PRIME) study, funded by the ] and Eli Lilly, tested the hypothesis that olanzapine might prevent the onset of psychosis in people at very high risk for ]. The study examined 60 patients with ] schizophrenia, who were at an estimated risk of 36–54% of developing schizophrenia within a year, and treated half with olanzapine and half with ].<ref>{{cite journal |
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| last = McGlashan | first = T.H. | authorlink = Thomas McGlashan | coauthors = et al. |
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| date = 1 May 2003 |
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| title = The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. I. Study rationale and design |
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| journal = Schizophrenia Research | volume = 61 | issue = 1 | pages = 7–18 |
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| publisher = ] | location = ] |
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| pmid = 12648731 | doi = 10.1016/S0920-9964(02)00439-5 |
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}}</ref> In this study, patients receiving olanzapine had a lower risk of progressing to psychosis, although the difference did not reach ]. Olanzapine was effective for treating the prodromal symptoms, but was associated with significant weight gain.<ref>{{cite journal |
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| last = McGlashan | first = Thomas H. | authorlink = Thomas McGlashan | coauthors = et al. |
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| year = 2006 | month = May |
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| title = Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis |
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| journal = ] | volume = 163 | issue = 5 | pages = 790–99 |
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| publisher = ] | location = ] |
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| pmid = 16648318 | doi = 10.1176/appi.ajp.163.5.790 |
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| url = http://ajp.psychiatryonline.org/cgi/content/full/163/5/790 |
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| accessdate = 2007-12-03 |
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}}</ref> |
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====Use in elderly==== |
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===Schizophrenia=== |
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The first-line psychiatric treatment for schizophrenia is antipsychotic medication.<ref>{{Cite web |title=Overview {{!}} Psychosis and schizophrenia in adults: prevention and management {{!}} Guidance {{!}} NICE |url=https://www.nice.org.uk/guidance/cg178 |access-date=30 November 2022 |website=www.nice.org.uk|date=12 February 2014 }}</ref> Olanzapine appears to be effective in reducing symptoms of schizophrenia, treating acute exacerbations, and treating early-onset schizophrenia.<ref name="Leucht2013">{{cite journal | vauthors = Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM | title = Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis | journal = Lancet | volume = 382 | issue = 9896 | pages = 951–962 | date = September 2013 | pmid = 23810019 | doi = 10.1016/S0140-6736(13)60733-3 | s2cid = 32085212 }}</ref><ref name=":0">{{cite journal | vauthors = Harvey RC, James AC, Shields GE | title = A Systematic Review and Network Meta-Analysis to Assess the Relative Efficacy of Antipsychotics for the Treatment of Positive and Negative Symptoms in Early-Onset Schizophrenia | journal = CNS Drugs | volume = 30 | issue = 1 | pages = 27–39 | date = January 2016 | pmid = 26801655 | doi = 10.1007/s40263-015-0308-1 | s2cid = 35702889 }}</ref><ref>{{cite journal | vauthors = Pagsberg AK, Tarp S, Glintborg D, Stenstrøm AD, Fink-Jensen A, Correll CU, Christensen R | title = Acute Antipsychotic Treatment of Children and Adolescents With Schizophrenia-Spectrum Disorders: A Systematic Review and Network Meta-Analysis | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 56 | issue = 3 | pages = 191–202 | date = March 2017 | pmid = 28219485 | doi = 10.1016/j.jaac.2016.12.013 }}</ref><ref>{{cite journal | vauthors = Osser DN, Roudsari MJ, Manschreck T | title = The psychopharmacology algorithm project at the Harvard South Shore Program: an update on schizophrenia | journal = Harvard Review of Psychiatry | volume = 21 | issue = 1 | pages = 18–40 | year = 2013 | pmid = 23656760 | doi = 10.1097/HRP.0b013e31827fd915 | s2cid = 22523977 }}</ref> The usefulness of maintenance therapy, however, is difficult to determine, as more than half of people in trials quit before the 6-week completion date.<ref>{{cite journal | vauthors = Duggan L, Fenton M, Rathbone J, Dardennes R, El-Dosoky A, Indran S | title = Olanzapine for schizophrenia | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD001359 | date = April 2005 | pmid = 15846619 | doi = 10.1002/14651858.CD001359.pub2 }}</ref> Treatment with olanzapine (like ]) may result in increased ] and increased glucose and cholesterol levels when compared to most other second-generation antipsychotic drugs used to treat schizophrenia.<ref name=":0" /><ref name="Komossa2010">{{cite journal | vauthors = Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Duggan L, Kissling W, Leucht S | title = Olanzapine versus other atypical antipsychotics for schizophrenia | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD006654 | date = March 2010 | pmid = 20238348 | pmc = 4169107 | doi = 10.1002/14651858.CD006654.pub2 }}</ref> |
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Citing an increased risk of ], in 2004 the ] (CSM) in the UK issued a warning that olanzapine and ], both atypical antipsychotic medications, should not be given to elderly patients with ]. In the U.S., olanzapine comes with a ] for increased risk of death in elderly patients. It is not approved for use in patients with dementia-related psychosis.<ref>{{cite web |
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| url = http://zyprexa.com/common_pages/safety.jsp |
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| title = Important Safety Information for Olanzapine |
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| accessdate = 2007-12-03 | year = 2007 |
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| work = Zyprexa package insert | publisher = Eli Lilly & Company |
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| quote = Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. ZYPREXA (olanzapine) is not approved for the treatment of elderly patients with dementia-related psychosis. |
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|archiveurl = http://web.archive.org/web/20071123225813/http://www.zyprexa.com/common_pages/safety.jsp <!-- Bot retrieved archive --> |archivedate = 2007-11-23}}</ref> However, a BBC investigation in June 2008 found that this advice was being widely ignored by British doctors.<ref>{{cite news |
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| publisher = BBC News |
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| date = 17 June 2008 |
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| url = http://news.bbc.co.uk/1/hi/programmes/file_on_4/7457132.stm |
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| accessdate = 2008-06-22}}</ref> |
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===Bipolar disorder=== |
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==Dosage and administration== |
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Olanzapine is recommended by the ] as a first-line therapy for the treatment of acute mania in bipolar disorder.<ref name=NICE2014B/> Other recommended first-line treatments are ], ], ], and ].<ref>{{cite journal | vauthors = McKeage K | title = Aripiprazole: a review of its use in the treatment of manic episodes in adolescents with bipolar I disorder | journal = CNS Drugs | volume = 28 | issue = 2 | pages = 171–183 | date = February 2014 | pmid = 24399490 | doi = 10.1007/s40263-013-0134-2 | s2cid = 199974 }}</ref> It is recommended in combination with ] as a first-line therapy for acute bipolar depression, and as a second-line treatment by itself for the maintenance treatment of bipolar disorder.<ref name=NICE2014B>{{cite web |url=http://www.nice.org.uk/guidance/cg185/chapter/1-recommendations |title=Bipolar disorder: the assessment and management of bipolar disorder in adults, children and young people in primary and secondary care |publisher=NICE |date=24 September 2014 |access-date=26 July 2016}}</ref> |
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])]] |
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The Network for Mood and Anxiety Treatments recommends olanzapine as a first-line maintenance treatment for bipolar disorder and the combination of olanzapine with fluoxetine as a second-line treatment for bipolar depression.<ref>{{cite journal | vauthors = Yatham LN, Kennedy SH, O'Donovan C, Parikh SV, MacQueen G, McIntyre RS, Sharma V, Beaulieu S | title = Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: update 2007 | journal = Bipolar Disorders | volume = 8 | issue = 6 | pages = 721–739 | date = December 2006 | pmid = 17156158 | doi = 10.1111/j.1399-5618.2006.00432.x | doi-access = free }}</ref> |
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Olanzapine is available as a tablet in strengths of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg and 20 mg. It also comes as an orally disintegrating wafer (known as Zydis), which dissolves on the tongue, in strengths of 5 mg, 10 mg, 15 mg and 20 mg. It is also available as a 10 mg vial for a rapid-acting ] for short-term acute use. |
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A review on the efficacy of olanzapine as maintenance therapy in people with bipolar disorder was published in 2006.<ref>{{cite journal | vauthors = Dando S, Tohen M | title = Olanzapine - relapse prevention following mania | journal = Journal of Psychopharmacology | volume = 20 | issue = 2 Suppl | pages = 31–38 | date = March 2006 | pmid = 16551670 | doi = 10.1177/1359786806063076 | s2cid = 34435730 }}</ref> A 2014 meta-analysis concluded that olanzapine with fluoxetine was the most effective among nine treatments for bipolar depression included in the analysis.<ref>{{cite journal | vauthors = Selle V, Schalkwijk S, Vázquez GH, Baldessarini RJ | title = Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics | journal = Pharmacopsychiatry | volume = 47 | issue = 2 | pages = 43–52 | date = March 2014 | pmid = 24549862 | doi = 10.1055/s-0033-1363258 | doi-access = free }}</ref> |
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Dose may be adjusted depending on the patient's response to the drug. The dose also will depend on certain medical problems the person may have. It is generally recommended to be taken once daily before bed as it is highly ]. However, sedation tends to diminish as treatment is pursued. |
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===Specific populations=== |
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==Pharmacology== |
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Olanzapine has a higher affinity for ] than ] receptors. Other affinities are (K<sub>i</sub>, nM): |
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====Pregnancy and lactation==== |
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* dopamine D<sub>1</sub>: 31 |
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Olanzapine is associated with the highest placental exposure of any atypical antipsychotic.<ref name=Maudsley>{{cite book | vauthors = Taylor D | title = The Maudsley prescribing guidelines in psychiatry | publisher = Wiley-Blackwell }}</ref> Despite this, the available evidence suggests it is safe during pregnancy, although the evidence is insufficiently strong to say anything with a high degree of confidence.<ref name=Maudsley/> Olanzapine is associated with weight gain, which according to recent studies, may put olanzapine-treated patients' offspring at a heightened risk for ] (e.g. ]).<ref>{{cite journal | vauthors = Rasmussen SA, Chu SY, Kim SY, Schmid CH, Lau J | title = Maternal obesity and risk of neural tube defects: a metaanalysis | journal = American Journal of Obstetrics and Gynecology | volume = 198 | issue = 6 | pages = 611–619 | date = June 2008 | pmid = 18538144 | doi = 10.1016/j.ajog.2008.04.021 }}</ref><ref>{{cite journal | vauthors = McMahon DM, Liu J, Zhang H, Torres ME, Best RG | title = Maternal obesity, folate intake, and neural tube defects in offspring | journal = Birth Defects Research. Part A, Clinical and Molecular Teratology | volume = 97 | issue = 2 | pages = 115–122 | date = February 2013 | pmid = 23404872 | doi = 10.1002/bdra.23113 }}</ref> Breastfeeding in women taking olanzapine is advised against because olanzapine is secreted in breast milk, with one study finding that the exposure to the infant is about 1.8% that of the mother.<ref name=TGA/> |
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* dopamine D<sub>2</sub>: 11 |
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* serotonin 5-HT<sub>2A</sub>: 4 |
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* serotonin 5-HT<sub>2C</sub>: 11 |
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* muscarinic M<sub>1</sub>: 1.9 |
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* adrenergic alpha<sub>1</sub>: 19 |
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====Elderly==== |
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Like most atypical antipsychotics, compared to the older typical ones, olanzapine has a lower affinity for ], ] and ] receptors. Olanzapine also exhibits weak affinity for GABA<sub>A</sub>, BZD receptor site<ref></ref> which may contribute slightly to its sedating properties.<ref> Definition of Olanzapine - National Cancer Institute</ref> |
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Citing an increased risk of ], in 2004, the ] in the UK issued a warning that olanzapine and risperidone, both atypical antipsychotic medications, should not be given to elderly patients with dementia. In the U.S., olanzapine comes with a ] for increased risk of death in elderly patients. It is not approved for use in patients with dementia-related psychosis.<ref>{{cite web| url = http://zyprexa.com/common_pages/safety.jsp| title = Important Safety Information for Olanzapine| access-date = 3 December 2007 | year = 2007| work = Zyprexa package insert | publisher = Eli Lilly & Company| quote = Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. ZYPREXA (olanzapine) is not approved for the treatment of elderly patients with dementia-related psychosis.| archive-url = https://web.archive.org/web/20071123225813/http://www.zyprexa.com/common_pages/safety.jsp <!-- Bot retrieved archive -->|archive-date = 23 November 2007}}</ref> A BBC investigation in June 2008 found that this advice was being widely ignored by British doctors.<ref>{{cite news| title = Doctors 'ignoring drugs warning'| work = BBC News| date = 17 June 2008| url = http://news.bbc.co.uk/1/hi/programmes/file_on_4/7457132.stm| access-date = 22 June 2008}}</ref> Evidence suggested that the elderly are more likely to experience weight gain on olanzapine compared to ] and ].<ref>{{cite journal | vauthors = Yeung EY, Chun S, Douglass A, Lau TE | title = Effect of atypical antipsychotics on body weight in geriatric psychiatric inpatients | journal = SAGE Open Medicine | volume = 5 | pages = 2050312117708711 | date = 8 May 2017 | pmid = 28540050 | pmc = 5431608 | doi = 10.1177/2050312117708711 }}</ref> |
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The mode of action of olanzapine's antipsychotic activity is unknown. It may involve antagonism at ] receptors. Antagonism of dopamine receptors is associated with ] such as ], and with therapeutic effects. Antagonizing H<sub>1</sub> histamine receptors causes sedation and may cause weight gain, although antagonistic actions at 5-HT<sub>2C</sub> receptors have also been implicated in weight gain. |
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== Adverse effects == |
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==Metabolism== |
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{{See also|List of adverse effects of olanzapine}} |
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Olanzapine is metabolized by the ] system isoenzymes 1A2 and 2D6 (minor pathway). Drug metabolism may be decreased or increased by agents that induce (e.g. cigarette smoke) or inhibit (e.g. ] or ]) CYP1A2 activity respectively. |
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The principal side effect of olanzapine is ], which may be profound in some cases and/or associated with derangement in blood-lipid and blood-sugar profiles (see section ]). A 2013 meta-analysis of the efficacy and tolerance of 15 antipsychotic drugs (APDs) found that it had the highest propensity for causing weight gain out of the 15 APDs compared with an SMD of 0.74.<ref name=Leucht2013/> Extrapyramidal side effects, although potentially serious, are infrequent to rare from olanzapine,<ref name="lexicomp">{{cite book | author = Lexi-Comp Inc. | date = 2010 | title = Lexi-Comp Drug Information Handbook | edition = 19th North American | location = Hudson, OH | publisher = Lexi-Comp Inc. | isbn = 978-1-59195-278-7 }}</ref> but may include tremors and muscle rigidity. |
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==Side effects, adverse reactions== |
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{{Original research|date=September 2009}} |
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As with all neuroleptic drugs, olanzapine can cause ] and rare, but life-threatening, ]. Similarly to other antipsychotics prolonged use is often associated with permanent brain damage.<ref name="breggin2">{{cite book |title=Brain disabling treatments in psychiatry |last=Breggin |first=P |authorlink= |coauthors= |year=2007 |publisher=Springer Publishing Compan |location= |isbn=082612934X |page= |pages=320 |url=http://books.google.fi/books?id=hBd0V7Ex8PUC&lpg=PR11&dq=neuroleptics%20withdrawal%20death&pg=PA85#v=onepage&q=neuroleptics%20withdrawal%20death&f=false |accessdate=}}</ref> |
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], ], ], ] and olanzapine, in comparison to other ] drugs, are less frequently associated with ]. Although these drugs can cause transient or sustained hyperprolactinaemia, the risk is much lower. Owing to its partial dopaminergic agonist effect, aripiprazole is likely to reduce prolactin levels and, in some patients, can cause hypoprolactinaemia.<ref>{{Cite journal | vauthors= Gupta S, Lakshmanan DA, Khastgir U, Nair R |date=2017 |title=Management of antipsychotic-induced hyperprolactinaemia |journal=BJPsych Advances |volume=23 |issue=4 |pages=278–286 |doi=10.1192/apt.bp.115.014928 |s2cid=80025501 |issn=2056-4678|doi-access=free }}</ref> Although olanzapine causes an early dose-related rise in prolactin, this is less frequent and less marked than that seen with haloperidol, and is usually transient. A rise in ] is seen in about half of patients on olanzapine compared to over 90% of those taking ], and enduring increases were less frequent in those taking olanzapine.<ref>{{Cite web |title=Hyperprolactinaemia With Antipsychotics |url=https://www.medsafe.govt.nz/profs/puarticles/hyperpro.htm |access-date=10 October 2022 |website=www.medsafe.govt.nz}}</ref> |
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Other recognised side effects may include: |
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*]; inability to remain still (restlessness)<ref>{{cite journal |author=Makkos Z, Csonka A |title= |language=Hungarian |journal=Neuropsychopharmacol Hung |volume=8 |issue=4 |pages=215–7 |year=2006 |month=December |pmid=17211056 |doi= |url=}}</ref> |
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*dry mouth |
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*] |
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*] |
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*] |
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*] |
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*] |
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*] |
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*] |
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*weight gain |
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*increased appetite |
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*runny nose |
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*impaired judgment, thinking, and motor skills |
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*impaired spatial orientation |
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*impaired responses to senses |
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*] |
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*trouble swallowing |
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*dental problems and discoloration of teeth |
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*missed periods |
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*problems with keeping body temperature regulated |
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*], lack of emotion |
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*Endocrine side effects have included ], ], and ] |
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*] |
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*Auditory Hallucinations |
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It is not recommended to be used by IM injection in acute myocardial infarction, bradycardia, recent heart surgery, severe hypotension, sick sinus syndrome, and unstable angina.<ref>{{cite web | author = Joint Formulary Committee | title = British National Formulary (online) | location = London | publisher = BMJ Group and Pharmaceutical | url = http://www.medicinescomplete.com | access-date = 2 February 2020 }}</ref> |
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===Metabolic effects=== |
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The ] requires all atypical antipsychotics to include a warning about the risk of developing ] and ], both of which are factors in the ]. These effects may be related to the drugs' ability to induce weight gain, although there are some reports of metabolic changes in the absence of weight gain.{{Citation needed|date=April 2009}} Studies have indicated that Olanzapine carries a greater risk of causing and exacerbating diabetes than another commonly prescribed atypical antipsychotic, Risperidone. Of all the atypical antipsychotics, olanzapine is one of the most likely to induce weight gain based on various measures.<ref name = Moyer>{{cite news |
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| first = Paula |
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| last = Moyer |
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| authorlink = Paula Moyer |
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| title = CAFE Study Shows Varying Benefits Among Atypical Antipsychotics |
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| url = http://www.medscape.com/viewarticle/515435 |
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| work = Medscape Medical News |
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| publisher = ] |
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| date = 2005-10-25 |
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| accessdate = 2007-12-03 |
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}} |
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</ref><ref name = Astra>{{cite web |
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| url = http://www.astrazenecaclinicaltrials.com/Article/526695.aspx |
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| title = Efficacy and Tolerability of Olanzapine, Quetiapine and Risperidone in the Treatment of First Episode Psychosis: A Randomised Double Blind 52 Week Comparison |
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| accessdate = 2007-12-03 |
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| author = AstraZeneca Pharmaceuticals |
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| date = 4 April 2006 |
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| work = AstraZeneca Clinical Trials |
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| publisher = ] PLC |
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| quote = At week 12, the olanzapine-treated group had more weight gain, a higher increase in ] ], and a higher proportion of patients with a BMI increase of at least 1 unit compared with the ] and ] groups (p<=0.01). |archiveurl = http://web.archive.org/web/20071113125708/http://www.astrazenecaclinicaltrials.com/Article/526695.aspx <!-- Bot retrieved archive --> |archivedate = 2007-11-13}} |
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</ref><ref>Wirshing DA, Wirshing WC, Kysar L, Berisford MA. (1999) Novel antipsychotics: comparison of weight gain liabilities. ''Journal of Clinical Psychology'' '''60''' 358-63</ref><ref name = NIMH>{{cite press release |
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| title = NIMH study to guide treatment choices for schizophrenia |
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| publisher = ] | date = 19 September 2005 |
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| url = http://www.eurekalert.org/pub_releases/2005-09/niom-nst091905.php |
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| accessdate = 2006-12-18 |
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}}</ref> The effect is not dose dependent. {{Dubious|Dose Dependent|date=February 2010}} Olanzapine may directly affect ] function, promoting fat deposition.<ref>{{cite journal |
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| last = Engl J, Rettenbacher M, Fleischhacker WW, Ebenbichler CF |
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| year = 2007 |
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| title = Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis. |
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| journal = Neuropsychopharmacology. Nov;32(11):2431-2; author reply 2433-4. |
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| volume = 32 |
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| issue = 11 |
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| pages = 2431–2}}</ref> There are some case reports of olanzapine-induced ].<ref>{{cite journal |
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| last = Fulbright |
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| first = April R. |
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| authorlink = April R. Fulbright |
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| year = 2006 |
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| title = Complete Resolution of Olanzapine-Induced Diabetic Ketoacidosis |
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| journal = Journal of Pharmacy Practice |
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| volume = 19 |
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| issue = 4 |
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| pages = 255–258 |
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| publisher = ] |
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| location = ] |
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| doi = 10.1177/0897190006294180 |
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| url = http://jpp.sagepub.com/cgi/content/abstract/19/4/255 |
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| format = abstract |
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| accessdate = 2007-12-02 |
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| quote = Olanzapine has been associated with diabetic ketoacidosis and also with weight gain, lipid abnormalities, and the development of type 2 diabetes. |
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| last2 = Breedlove |
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| first2 = K. T. |
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}}</ref> Olanzapine may decrease ]<ref>{{cite journal |
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| last = Sacher J, Mossaheb N, Spindelegger C, Klein N, Geiss-Granadia T, Sauermann R, Lackner E, Joukhadar C, Müller M, Kasper S. |
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| year = 2008 |
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| title = Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers. |
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| journal = Neuropsychopharmacology |
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| volume = 33 |
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| issue = 7 |
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| pages = 1633–41 |
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| accessdate = 2008-04-21 |
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| pmid = 17712347 |
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| first1 = J |
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| last2 = Mossaheb |
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| first2 = N |
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| last3 = Spindelegger |
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| first3 = C |
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| last4 = Klein |
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| first4 = N |
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| last5 = Geiss-Granadia |
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| first5 = T |
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| last6 = Sauermann |
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| first6 = R |
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| last7 = Lackner |
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| first7 = E |
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| last8 = Joukhadar |
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| first8 = C |
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| last9 = Müller |
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| first9 = M |
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| doi = 10.1038/sj.npp.1301541}}</ref> though one 3-week study seems to refute this.<ref>{{cite journal |
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| last = Sowell |
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| first = Margaret |
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| authorlink = Margaret Sowell |
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| coauthors = et al. |
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| date = August 8, 2003 |
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| title = Evaluation of Insulin Sensitivity in Healthy Volunteers Treated with Olanzapine, Risperidone, or Placebo: A Prospective, Randomised Study Using the Two-Step Hyperinsulinemic, Euglycemic Clamp |
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| journal = Journal of Clinical Endocrinology & Metabolism |
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| volume = 88 |
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| issue = 12 |
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| pages = 5875–5880 |
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| publisher = The Endocrine Society |
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| url = http://jcem.endojournals.org/cgi/content/full/88/12/5875 |
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| accessdate = 2007-12-02 |
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| quote = In summary, this study did not demonstrate significant changes in insulin sensitivity in healthy subjects after 3 wk of treatment with olanzapine or risperidone. |
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| doi = 10.1210/jc.2002-021884 |
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| pmid = 14671184 |
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}}</ref> It may also increase ] levels.<ref name = Astra /> |
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Several patient groups are at a heightened risk of side effects from olanzapine and antipsychotics in general. Olanzapine may produce nontrivial ] in people with ]. Likewise, the elderly are at a greater risk of falls and accidental injury. Young males appear to be at heightened risk of ] reactions, although these are relatively rare with olanzapine. Most antipsychotics, including olanzapine, may disrupt the body's natural thermoregulatory systems, thus permitting excursions to dangerous levels when situations (exposure to heat, strenuous exercise) occur.<ref name=TGA>{{cite web|title=Product Information Olanzapine Sandoz 2.5mg/5mg/7.5mg/10mg/15mg/20mg Film-coated Tablets |work=TGA eBusiness Services|publisher=Sandoz Pty Ltd|date=8 June 2012|access-date=26 November 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-02375-3|format=PDF}}</ref><ref name=MSR>{{cite web|title=Zyprexa, Zyprexa Relprevv (olanzapine) dosing, indications, interactions, adverse effects, and more|access-date=26 November 2013|work=Medscape Reference|publisher=WebMD|url=http://reference.medscape.com/drug/zyprexa-relprevv-olanzapine-342979#showall}}</ref><ref>{{cite journal | vauthors = Stöllberger C, Lutz W, Finsterer J | title = Heat-related side-effects of neurological and non-neurological medication may increase heatwave fatalities | journal = European Journal of Neurology | volume = 16 | issue = 7 | pages = 879–882 | date = July 2009 | pmid = 19453697 | doi = 10.1111/j.1468-1331.2009.02581.x | s2cid = 25016607 }}</ref><ref name="Zyprexa FDA label" /><ref name=EMC>{{cite web | title= Zyprexa 10 mg coated tablets Summary of Product Characteristics (SmPC) | website=(emc) | date=2 February 2024 | url=https://www.medicines.org.uk/emc/product/15471/smpc | access-date=26 October 2024}}</ref> |
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Recent studies have established : |
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* that Olanzapine and Clozapine disturb the metabolism by making the body take preferentially its energy from fat (instead of privileging carbohydrates). Thus, levels of carbohydrates remaining high, the body would develop insulin resistance (reduction of insulin sensitivity).<ref>{{cite journal | author1 = Albaugh VL | author2 = Vary TC | author3 = Ilkayeva O | author4 = Wener BR | author5 = Maresca KP | author6 = Joyal JL | author7 = Breazeale S | author8 = Elich TD | author9 = Lang CH | year = 2010 | title = Atypical Antipsychotics Rapidly and Inappropriately Switch Peripheral Fuel Utilization to Lipids, Impairing Metabolic Flexibility in Rodents | journal = Schizophrenia Bulletin | doi = 10.1093/schbul/sbq053 | pmid = 20494946}}</ref> |
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* that Olanzapine promotes fat accumulation : due to disturbances in fat metabolism, rodents become fatter (but don't have their weight increasing at first). Being fatter, they do less exercise, burning less fat and gaining weight.<ref>{{cite journal | author1 = Albaugh VL | author2 = Judson JG | author3 = She P | author4 = Lang CH | author5 = Maresca KP | author6 = Joyal JL | author7 = Lynch CJ | year = 2010 | title = Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis | journal = Molecular Psychiatry | doi = 10.1038/mp.2010.33 | pmc = 2892549 | pmid = 20308992}}</ref> |
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Other side effects possibly include ], ], ], and erectile dysfunction (impotence).<ref>{{cite web|title=Olanzapine Monograph for Professionals - Drugs.com|url=https://www.drugs.com/monograph/olanzapine.html|website=Drugs.com|access-date=24 March 2017}}</ref> |
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Despite weight gain, a large multi-center randomized ] study found that olanzapine was better at controlling symptoms because patients were more likely to remain on olanzapine than the other drugs.<ref>{{cite news |
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| first = Benedict |
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| last = Carey |
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| authorlink = Benedict Carey |
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| title = Little Difference Found in Schizophrenia Drugs |
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| url = http://www.nytimes.com/2005/09/20/health/psychology/20drug.html |
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| work = ] |
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| publisher = The New York Times Company |
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| date = September 20, 2005 |
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| accessdate = 2007-12-03 |
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}}</ref> One small, open-label, non-randomized study suggest that taking olanzapine by orally dissolving tablets may induce less weight gain,<ref>{{cite journal |author=de Haan L, van Amelsvoort T, Rosien K, Linszen D |title=Weight loss after switching from conventional olanzapine tablets to orally disintegrating olanzapine tablets |journal=Psychopharmacology (Berl) |volume=175 |issue=3 |pages=389–90 |year=2004 |pmid=15322727 |doi=10.1007/s00213-004-1951-2}}</ref> but this has not been substantiated in a blinded experimental setting. |
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===Animal Toxicology=== |
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=== Drug-induced OCD === |
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{{main|Obsessive–compulsive disorder#Drug-induced OCD}} |
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In a placebo-compared study of six ] monkeys receiving olanzapine between 17 and 27 months, a significant brain volume and weight decreases (8-11%) were detected.<!-- |
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Many different types of medication can create or induce pure obsessive-compulsive disorder (OCD) in people who have never had symptoms before.{{medcn|date=October 2024}} |
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--><ref name="pmid15756305">{{cite journal |author=Dorph-Petersen KA, Pierri JN, Perel JM, Sun Z, Sampson AR, Lewis DA |title=The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys |journal=] |volume=30 |issue=9 |pages=1649–61 |year=2005 |month=September |pmid=15756305 |doi=10.1038/sj.npp.1300710}}</ref><!-- |
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===Metabolic effects=== |
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--> In latter studies of the stored samples, the changes were attributed to astrocyte and oligodendrocyte loss,<!-- |
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The US ] (FDA) requires atypical antipsychotics to include a warning about the risk of developing ] and ], both of which are factors in the ]. These effects may be related to the drugs' ability to induce weight gain, although some reports have been made of metabolic changes in the absence of weight gain.<ref>{{cite journal | vauthors = Ramankutty G | title = Olanzapine-induced destabilization of diabetes in the absence of weight gain | journal = Acta Psychiatrica Scandinavica | volume = 105 | issue = 3 | pages = 235–6; discussion 236–7 | date = March 2002 | pmid = 11939979 | doi = 10.1034/j.1600-0447.2002.2c257a.x | s2cid = 5965031 }}</ref><ref>{{cite journal | vauthors = Lambert MT, Copeland LA, Sampson N, Duffy SA | title = New-onset type-2 diabetes associated with atypical antipsychotic medications | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 30 | issue = 5 | pages = 919–923 | date = July 2006 | pmid = 16581171 | doi = 10.1016/j.pnpbp.2006.02.007 | s2cid = 24739534 }}</ref> Studies have indicated that olanzapine carries a greater risk of causing and exacerbating diabetes than another commonly prescribed atypical antipsychotic, risperidone. Of all the atypical antipsychotics, olanzapine is one of the most likely to induce weight gain based on various measures.<ref name=Moyer>{{cite news| vauthors = Moyer P | title = CAFE Study Shows Varying Benefits Among Atypical Antipsychotics| url = http://www.medscape.com/viewarticle/515435| work = Medscape Medical News| publisher = ]| date = 25 October 2005| access-date = 3 December 2007 }} |
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</ref><ref name=Astra>{{cite web| url = http://www.astrazenecaclinicaltrials.com/Article/526695.aspx| title = Efficacy and Tolerability of Olanzapine, Quetiapine and Risperidone in the Treatment of First Episode Psychosis: A Randomised Double Blind 52 Week Comparison| access-date = 3 December 2007| author = AstraZeneca Pharmaceuticals| date = 4 April 2006| work = AstraZeneca Clinical Trials| publisher = ] PLC| quote = At week 12, the olanzapine-treated group had more weight gain, a higher increase in ] ], and a higher proportion of patients with a BMI increase of at least 1 unit compared with the ] and ] groups (p<=0.01).|archive-url = https://web.archive.org/web/20071113125708/http://www.astrazenecaclinicaltrials.com/Article/526695.aspx <!-- Bot retrieved archive --> |archive-date = 13 November 2007}} |
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</ref><ref>{{cite journal | vauthors = Wirshing DA, Wirshing WC, Kysar L, Berisford MA, Goldstein D, Pashdag J, Mintz J, Marder SR | title = Novel antipsychotics: comparison of weight gain liabilities | journal = The Journal of Clinical Psychiatry | volume = 60 | issue = 6 | pages = 358–363 | date = June 1999 | pmid = 10401912 | doi = 10.4088/JCP.v60n0602 }}</ref><ref name=NIMH>{{cite press release| title = NIMH study to guide treatment choices for schizophrenia| publisher = ] | date = 19 September 2005| url = http://www.eurekalert.org/pub_releases/2005-09/niom-nst091905.php| access-date = 18 December 2006}}</ref><ref>{{cite journal | vauthors = McEvoy JP, Lieberman JA, Perkins DO, Hamer RM, Gu H, Lazarus A, Sweitzer D, Olexy C, Weiden P, Strakowski SD | title = Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison | journal = The American Journal of Psychiatry | volume = 164 | issue = 7 | pages = 1050–1060 | date = July 2007 | pmid = 17606657 | doi = 10.1176/ajp.2007.164.7.1050 }}</ref> The effect is dose dependent in humans<ref>{{cite journal | vauthors = Nemeroff CB | title = Dosing the antipsychotic medication olanzapine | journal = The Journal of Clinical Psychiatry | volume = 58 | issue = Suppl 10 | pages = 45–49 | year = 1997 | pmid = 9265916 }}</ref> and animal models of olanzapine-induced metabolic side effects. There are some case reports of olanzapine-induced ].<ref>{{cite journal|doi=10.1177/0897190006294180 |title=Complete Resolution of Olanzapine-Induced Diabetic Ketoacidosis |year=2006| vauthors = Fulbright AR, Breedlove KT |s2cid=73047103 |journal=Journal of Pharmacy Practice |volume=19 |issue=4 |pages=255–8}}</ref> Olanzapine may decrease ],<ref>{{cite journal | vauthors = Chiu CC, Chen CH, Chen BY, Yu SH, Lu ML | title = The time-dependent change of insulin secretion in schizophrenic patients treated with olanzapine | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 34 | issue = 6 | pages = 866–870 | date = August 2010 | pmid = 20394794 | doi = 10.1016/j.pnpbp.2010.04.003 | s2cid = 22445875 }}</ref><ref>{{cite journal | vauthors = Sacher J, Mossaheb N, Spindelegger C, Klein N, Geiss-Granadia T, Sauermann R, Lackner E, Joukhadar C, Müller M, Kasper S | title = Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers | journal = Neuropsychopharmacology | volume = 33 | issue = 7 | pages = 1633–1641 | date = June 2008 | pmid = 17712347 | doi = 10.1038/sj.npp.1301541 | doi-access = free }}</ref> though one 3-week study seems to refute this.<ref>{{cite journal | vauthors = Sowell M, Mukhopadhyay N, Cavazzoni P, Carlson C, Mudaliar S, Chinnapongse S, Ray A, Davis T, Breier A, Henry RR, Dananberg J | title = Evaluation of insulin sensitivity in healthy volunteers treated with olanzapine, risperidone, or placebo: a prospective, randomized study using the two-step hyperinsulinemic, euglycemic clamp | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 12 | pages = 5875–5880 | date = December 2003 | pmid = 14671184 | doi = 10.1210/jc.2002-021884 | author-link3 = Patrizia Cavazzoni | doi-access = free }}</ref> It may also increase ] levels.<ref name=Astra /> |
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Despite weight gain, a large multicenter, randomized ] study found that olanzapine was better at controlling symptoms because patients were more likely to remain on olanzapine than the other drugs.<ref>{{cite news| vauthors = Carey B | author-link = Benedict Carey | title = Little Difference Found in Schizophrenia Drugs| url = https://www.nytimes.com/2005/09/20/health/psychology/20drug.html| work = ]| date = 20 September 2005| access-date = 3 December 2007 }}</ref> One small, open-label, nonrandomized study suggests that taking olanzapine by orally dissolving tablets may induce less weight gain,<ref>{{cite journal | vauthors = de Haan L, van Amelsvoort T, Rosien K, Linszen D | title = Weight loss after switching from conventional olanzapine tablets to orally disintegrating olanzapine tablets | journal = Psychopharmacology | volume = 175 | issue = 3 | pages = 389–390 | date = September 2004 | pmid = 15322727 | doi = 10.1007/s00213-004-1951-2 | s2cid = 38751442 }}</ref> but this has not been substantiated in a blinded experimental setting. |
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===Post-injection delirium/sedation syndrome=== |
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Postinjection delirium/sedation syndrome (PDSS) is a rare syndrome that is specific to the long-acting injectable formulation of olanzapine, olanzapine ].<ref name="Luedecke et al">{{cite journal | vauthors = Luedecke D, Schöttle D, Karow A, Lambert M, Naber D | title = Post-injection delirium/sedation syndrome in patients treated with olanzapine pamoate: mechanism, incidence, and management | journal = CNS Drugs | volume = 29 | issue = 1 | pages = 41–46 | date = January 2015 | pmid = 25424243 | doi = 10.1007/s40263-014-0216-9 | s2cid = 10928442 }}</ref> The incidence of PDSS with olanzapine pamoate is estimated to be 0.07% of administrations, and is unique among other second-generation, long-acting antipsychotics (e.g. ]), which do not appear to carry the same risk.<ref name="Luedecke et al" /> PDSS is characterized by symptoms of ] (e.g. confusion, ], and ]) and sedation.<ref name="Luedecke et al" /> Most people with PDSS exhibit both delirium and sedation (83%).<ref name="Luedecke et al" /> Although less specific to PDSS, a majority of cases (67%) involved a feeling of ].<ref name="Luedecke et al" /> PDSS may occur due to accidental injection and absorption of olanzapine pamoate into the bloodstream, where it can act more rapidly, as opposed to slowly distributing out from muscle tissue.<ref name="Luedecke et al" /> Using the proper, intramuscular-injection technique for olanzapine pamoate helps to decrease the risk of PDSS, though it does not eliminate it entirely.<ref name="Luedecke et al" /> This is why the FDA advises that people who are injected with olanzapine pamoate be watched for 3 hours after administration, in the event that PDSS occurs.<ref name="Luedecke et al" /> |
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===Animal toxicology=== |
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--><ref name="pmid17945195">{{cite journal |author=Konopaske GT, Dorph-Petersen KA, Sweet RA, Pierri JN, Zhang W, Sampson AR, Lewis DA |title=Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys |journal=] |volume=63 |issue=8 |pages=759–65 |year=2008 |month=April |pmid=17945195 |pmc=2386415 |doi=10.1016/j.biopsych.2007.08.018 |url=http://linkinghub.elsevier.com/retrieve/pii/S0006-3223(07)00847-5}}</ref><!-- |
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Olanzapine has demonstrated carcinogenic effects in multiple studies when exposed chronically to female mice and rats, but not male mice and rats. The tumors found were in either the liver or mammary glands of the animals.<ref name="pmid19410629">{{cite journal | vauthors = Brambilla G, Mattioli F, Martelli A | title = Genotoxic and carcinogenic effects of antipsychotics and antidepressants | journal = Toxicology | volume = 261 | issue = 3 | pages = 77–88 | date = July 2009 | pmid = 19410629 | doi = 10.1016/j.tox.2009.04.056 | bibcode = 2009Toxgy.261...77B }}</ref> |
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===Discontinuation=== |
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--> with the neurons spared but positioned more closely compared to the controls. {{Clarify|date=March 2009}} |
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The ] recommends a gradual withdrawal when ] to avoid acute withdrawal syndrome or rapid relapse.<ref name="Group 2009 192">{{cite book |editor1-first=BMJ | editor = Joint Formulary Committee | title = British National Formulary | edition = 57 | date = March 2009 |publisher=Royal Pharmaceutical Society of Great Britain |location=United Kingdom |isbn=978-0-85369-845-6 |page=192 |chapter=4.2.1 |quote=Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.}}</ref> Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.<ref name=Had2004>{{cite book | vauthors = Haddad P, Haddad PM, Dursun S, Deakin B |title=Adverse Syndromes and Psychiatric Drugs: A Clinical Guide |date=2004 |publisher=OUP Oxford |isbn=978-0-19-852748-0 |pages=207–216 |url=https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 }}</ref> Other symptoms may include restlessness, increased sweating, and trouble sleeping.<ref name=Had2004/> Less commonly, ], numbness, or muscle pains may occur.<ref name=Had2004/> Symptoms generally resolve after a short time.<ref name=Had2004/> |
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However according to this study the neurons do not seem to be completely spared. The gray matter shrinking found was 14.6%, but the neuron density increase was only 10.2% which corresponds to approximately a loss of 5% of the neurons.{{Citation needed|date=April 2010}} |
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Tentative evidence indicates that discontinuation of antipsychotics can result in psychosis, as a temporary withdrawal symptom.<ref>{{cite journal | vauthors = Moncrieff J | title = Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse | journal = Acta Psychiatrica Scandinavica | volume = 114 | issue = 1 | pages = 3–13 | date = July 2006 | pmid = 16774655 | doi = 10.1111/j.1600-0447.2006.00787.x | s2cid = 6267180 }}</ref> It may also result in reoccurrence of the condition that is being treated.<ref>{{cite book | vauthors = Sacchetti E, Vita A, Siracusano A, Fleischhacker W |title=Adherence to Antipsychotics in Schizophrenia |date=2013 |publisher=Springer Science & Business Media |isbn=978-88-470-2679-7 |page=85 |url=https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85 }}</ref> Rarely, tardive dyskinesia can occur when the medication is stopped.<ref name=Had2004/> |
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Olanzapine has demonstrated carcinogenic effects in multiple studies when exposed chronically to female mice and rats, but not male mice and rats. The tumors found were in either the liver or mammary glands of the animals.<ref name="pmid19410629">{{cite journal |author=Giovanni Brambilla, Francesca Mattioli, Antonietta Martelli |title=Genotoxic and carcinogenic effects of antipsychotics and antidepressants |journal=] |volume=261 |issue=3 |pages=77–88 |year=2009 |month=June |pmid=19410629 |doi=10.1016/j.tox.2009.04.056 |url=http://linkinghub.elsevier.com/retrieve/pii/S0300-483X(09)00232-7}}</ref> |
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==Overdose== |
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==Overdose== |
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Symptoms of an overdose include ], ], ], decreased consciousness and coma. Death has been reported after an acute overdose of 450 mg, but also survival after an acute overdose of 1500 mg.<ref name="RxList">{{cite web |
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Symptoms of an overdose include ], ], ], decreased consciousness, and coma. Death has been reported after an acute overdose of 450 mg, but also survival after an acute overdose of 2000 mg.<ref name="RxList">{{cite web |url = http://www.rxlist.com/cgi/generic/symbyax_od.htm |title = Symbyax (Olanzapine and fluoxetine) drug overdose and contraindication information |access-date = 3 December 2007 |year = 2007 |work = RxList: The Internet Drug Index |publisher = ] |url-status = dead|archive-url = https://web.archive.org/web/20071214235622/http://www.rxlist.com/cgi/generic/symbyax_od.htm |archive-date = 14 December 2007 }}</ref> Fatalities generally have occurred with olanzapine plasma concentrations greater than 1000 ng/mL '']'', with concentrations up to 5200 ng/mL recorded (though this might represent confounding by dead tissue, which may release olanzapine into the blood upon death).<ref name="Schwenger Review" /> No specific antidote for olanzapine overdose is known, and even physicians are recommended to call a certified ] for information on the treatment of such a case.<ref name="RxList"/> |
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Olanzapine is considered moderately toxic in overdose, more toxic than quetiapine, aripiprazole, and the ], and less toxic than the ] and ].<ref name =Maudsley/> |
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| url = http://www.rxlist.com/cgi/generic/symbyax_od.htm |
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| title = Symbyax (Olanzapine and fluoxetine) drug overdose and contraindication information |
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| accessdate = 2007-12-03 |
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| year = 2007 |
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| work = RxList: The Internet Drug Index |
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| publisher = ] |
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}}</ref> There is no known specific antidote for olanzapine overdose, and even physicians are recommended to call a certified ] for information on the treatment of such a case.<ref name="RxList"/> |
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Perscription should be kept in small quantity to reduce risk overdose as acute bipolar disorder and schizophrenic patients can be at a high risk of suicide(Eli Lilly 2010) |
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==Interactions== |
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==Controversy, lawsuits and settlements== |
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Drugs or agents that increase the activity of the enzyme ], notably tobacco smoke, may significantly increase hepatic first-pass clearance of olanzapine; conversely, drugs that inhibit CYP1A2 activity (examples: ], ]) may reduce olanzapine clearance.<ref name="olanzapinepi">{{cite web| title = Olanzapine Prescribing Information| publisher = Eli Lilly and Company| date = 19 March 2009| url = http://pi.lilly.com/us/zyprexa-pi.pdf| access-date = 6 September 2009}}</ref> ], a known enzyme inducer, has decreased the concentration/dose ratio of olanzapine by 33% compared to olanzapine alone.<ref name="Schwenger Review" /> Another enzyme inducer, ], has also been shown to decrease the body's exposure to olanzapine, due to its induction of the enzymes CYP1A2 and ] (UGT).<ref name="Schwenger Review" /> |
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{{See|Eli Lilly Controversy}} |
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] increases the total exposure (]) and ] of olanzapine.<ref name="Schwenger Review" /> Although olanzapine's metabolism includes the minor metabolic pathway of ], the presence of the CYP2D6 inhibitor ] does not have a clinically significant effect on olanzapine's clearance.<ref name="Schwenger Review" /> |
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According to a '']'' article published on December 17, 2006,<ref></ref> "Eli Lilly has engaged in a decade-long effort to play down the health risks of Zyprexa, its best-selling medication for schizophrenia, according to hundreds of internal Lilly documents and e-mail messages among top company managers", most of which had been disclosed as the result of lawsuits by individuals who had taken the drug, though other documents had been stolen.<ref name=finaljudgement/> These had been sent to a number of journalists by a lawyer advocate for individuals with a psychiatric diagnosis opposed to forced psychiatric treatment. Eli Lilly filed a protection order to stop the dissemination of certain Eli Lilly documents about Zyprexa which they, and the judge, believed to be confidential and "not generally appropriate for public consumption".<ref name=finaljudgement></ref> Temporary injunctions required those who had been received the documents to return them and that the documents be removed from websites which had posted them.<ref></ref> In his final judgement, Judge Weinstein issued a permanent judgement against further dissemination of the documents and requiring their return by a number of parties named by Lilly.<ref name=finaljudgement/> These health risks include an increased risk for diabetes through Zyprexa's links to obesity and its tendency to raise ]. Zyprexa is Lilly’s top-selling drug, with sales of $4.2 billion last year. |
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Olanzapine has been used as a ] to block the effects of ]s like ] and ] (LSD).<ref name="YatesMelon2024">{{cite journal | vauthors = Yates G, Melon E | title = Trip-killers: a concerning practice associated with psychedelic drug use | journal = Emerg Med J | volume = 41 | issue = 2 | pages = 112–113 | date = January 2024 | pmid = 38123961 | doi = 10.1136/emermed-2023-213377 | url = }}</ref><ref name="Suran2024">{{cite journal | vauthors = Suran M | title = Study Finds Hundreds of Reddit Posts on "Trip-Killers" for Psychedelic Drugs | journal = JAMA | volume = 331 | issue = 8 | pages = 632–634 | date = February 2024 | pmid = 38294772 | doi = 10.1001/jama.2023.28257 | url = }}</ref> |
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The documents, given to ''The New York Times'' by ], show that Lilly executives kept important information from doctors about Zyprexa’s links to obesity and its tendency to raise blood sugar — both known risk factors for diabetes. ''The Times'' of London also obtained copies of the documents and reported that as early as October 1998, Lilly considered the risk of drug-induced obesity to be a "top threat" to Zyprexa sales.<ref name=timeso>, The Times (London), January 23, 2007</ref> In another document, dated October 9, 2000, senior Lilly research physician Robert Baker noted that an academic advisory board he belonged to was "quite impressed by the magnitude of weight gain on olanzapine and implications for glucose."<ref name=timeso/> |
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==Pharmacology== |
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Lilly’s own published data, which it told its sales representatives to play down in conversations with doctors, has shown that 30 percent of patients taking Zyprexa gain 22 pounds or more after a year on the drug, another study showed 16% of Zyprexa patients gained at least 30 kg (66 pounds) in one year, and some patients have reported gaining 100 pounds or more. But Lilly was concerned that Zyprexa’s sales would be hurt if the company was more forthright about the fact that the drug might cause unmanageable weight gain or ], according to the documents, which cover the period 1995 to 2004. In 2006, Lilly paid $700 million to settle 18,000 lawsuits from people who said they had developed diabetes or other diseases after taking Zyprexa. Thousands more suits are still pending.<ref> Mother Wonders if Psychosis Drug Helped Kill Son, New York Times, January 4, 2007</ref> |
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===Pharmacodynamics=== |
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In 2002, British and Japanese regulatory agencies warned that Zyprexa may be linked to diabetes, but even after the FDA issued a similar warning in 2003, Lilly did not publicly disclose their own findings. |
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{{See also|Atypical antipsychotic#Pharmacodynamics|Antipsychotic#Comparison of medications}} |
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{| class="wikitable floatright" style="font-size:small;" |
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Eli Lilly agreed on January 4, 2007 to pay up to $500 million to settle 18,000 lawsuits from people who claimed they developed diabetes or other diseases after taking Zyprexa. Including earlier settlements over Zyprexa, Lilly has now agreed to pay at least $1.2 billion to 28,500 people who claim they were injured by the drug. At least 1,200 suits are still pending, the company said. About 20 million people worldwide have taken Zyprexa since its introduction in 1996.<ref> Lilly to Pay Up to $500 Million to Settle Claims. The New York Times, January 4, 2007</ref> On January 8, 2007, Judge ] refused the ]'s motion to stay his order.<ref></ref> |
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|+ Olanzapine<ref name="PDSP">{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP)|author1-link=Bryan Roth | vauthors = Roth BL, Driscol J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=olanzapine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}</ref> |
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! Site !! K<sub>i</sub> (nM) !! Action !! Ref |
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| {{abbrlink|SERT|Serotonin transporter}} || ≥3,676 || {{abbr|ND|No data}} || <ref name="PDSP" /><ref name="pmid18595716" /> |
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| {{abbrlink|NET|Norepinephrine transporter}} || >10,000 || {{abbr|ND|No data}} || <ref name="PDSP" /> |
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| {{abbrlink|DAT|Dopamine transporter}} || >10,000 || {{abbr|ND|No data}} || <ref name="PDSP" /> |
|
|
|- |
|
|
| ] || 2,063–2,720 || Antagonist || <ref name="pmid12629531">{{cite journal | vauthors = Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, Jayathilake K, Meltzer HY, Roth BL | title = H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs | journal = Neuropsychopharmacology | volume = 28 | issue = 3 | pages = 519–526 | date = March 2003 | pmid = 12629531 | doi = 10.1038/sj.npp.1300027 | doi-access = free }}</ref><ref name="pmid8935801" /> |
|
|
|- |
|
|
| ] || 509–660 || {{abbr|ND|No data}} || <ref name="PDSP" /><ref name="pmid8935801" /> |
|
|
|- |
|
|
| ] || 540–1,582 || {{abbr|ND|No data}} || <ref name="PDSP" /><ref name="pmid8935801" /> |
|
|
|- |
|
|
| ] || 2,010–2,408 || {{abbr|ND|No data}} || <ref name="PDSP" /><ref name="pmid8935801" /> |
|
|
|- |
|
|
| ] || 310 || {{abbr|ND|No data}} || <ref name="pmid8935801" /> |
|
|
|- |
|
|
| ] || 1.32–24.2 || Inverse agonist || <ref name="pmid16314884">{{cite journal | vauthors = Davies MA, Setola V, Strachan RT, Sheffler DJ, Salay E, Hufeisen SJ, Roth BL | title = Pharmacologic analysis of non-synonymous coding h5-HT2A SNPs reveals alterations in atypical antipsychotic and agonist efficacies | journal = The Pharmacogenomics Journal | volume = 6 | issue = 1 | pages = 42–51 | year = 2006 | pmid = 16314884 | doi = 10.1038/sj.tpj.6500342 | doi-access = free }}</ref><ref name="pmid8997630" /> |
|
|
|- |
|
|
| ] || 11.8–12.0 || Inverse agonist || <ref name="pmid8632342">{{cite journal | vauthors = Wainscott DB, Lucaites VL, Kursar JD, Baez M, Nelson DL | title = Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 276 | issue = 2 | pages = 720–727 | date = February 1996 | pmid = 8632342 }}</ref><ref name="pmid10227113">{{cite journal | vauthors = Bymaster FP, Nelson DL, DeLapp NW, Falcone JF, Eckols K, Truex LL, Foreman MM, Lucaites VL, Calligaro DO | title = Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and alpha 1-adrenergic receptors in vitro | journal = Schizophrenia Research | volume = 37 | issue = 1 | pages = 107–122 | date = May 1999 | pmid = 10227113 | doi = 10.1016/s0920-9964(98)00146-7 | s2cid = 19891653 }}</ref> |
|
|
|- |
|
|
| ] || 6.4–29 || Inverse agonist || <ref name="pmid8997630" /><ref name="pmid10227113" /> |
|
|
|- |
|
|
| ] || 202 || Antagonist || <ref name="PDSP" /> |
|
|
|- |
|
|
| ] || 1,212 || Full Agonist || <ref name="PDSP" /> |
|
|
|- |
|
|
| ] || 6.0–42 || Antagonist || <ref name="PDSP" /><ref name="pmid14642972">{{cite journal | vauthors = Bymaster FP, Felder CC, Tzavara E, Nomikos GG, Calligaro DO, Mckinzie DL | title = Muscarinic mechanisms of antipsychotic atypicality | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 27 | issue = 7 | pages = 1125–1143 | date = October 2003 | pmid = 14642972 | doi = 10.1016/j.pnpbp.2003.09.008 | s2cid = 28536368 }}</ref> |
|
|
|- |
|
|
| ] || 105–365 || Antagonist || <ref name="PDSP" /><ref name="pmid15771415">{{cite journal | vauthors = Fernández J, Alonso JM, Andrés JI, Cid JM, Díaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA | title = Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents | journal = Journal of Medicinal Chemistry | volume = 48 | issue = 6 | pages = 1709–1712 | date = March 2005 | pmid = 15771415 | doi = 10.1021/jm049632c }}</ref> |
|
|
|- |
|
|
| ] || 109–115 || Antagonist || <ref name="PDSP" /><ref name="pmid12629531" /> |
|
|
|- |
|
|
| ] || 263 || Antagonist || <ref name="PDSP" /> |
|
|
|- |
|
|
| ] || 192–470 || Antagonist || <ref name="pmid8935801" /><ref name="pmid15771415" /> |
|
|
|- |
|
|
| ] || 82–180 || Antagonist || <ref name="pmid12629531" /><ref name="pmid8935801" /> |
|
|
|- |
|
|
| ] || 29–210 || Antagonist || <ref name="pmid12629531" /><ref name="pmid8935801" /> |
|
|
|- |
|
|
| ] || >10,000 || {{abbr|ND|No data}} || <ref name="PDSP" /><ref name="pmid8935801" /> |
|
|
|- |
|
|
| ] || >10,000 || {{abbr|ND|No data}} || <ref name="PDSP" /><ref name="pmid8935801" /> |
|
|
|- |
|
|
| ] || 35–118 || Antagonist || <ref name="pmid8997630" /><ref name="pmid15771415"/> |
|
|
|- |
|
|
| ] || 3.00–106 || Antagonist || <ref name="pmid9577836">{{cite journal | vauthors = Seeman P, Tallerico T | title = Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors | journal = Molecular Psychiatry | volume = 3 | issue = 2 | pages = 123–134 | date = March 1998 | pmid = 9577836 | doi = 10.1038/sj.mp.4000336 | doi-access = free }}</ref><ref name="pmid16135699">{{cite journal | vauthors = Burstein ES, Ma J, Wong S, Gao Y, Pham E, Knapp AE, Nash NR, Olsson R, Davis RE, Hacksell U, Weiner DM, Brann MR | title = Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 315 | issue = 3 | pages = 1278–1287 | date = December 2005 | pmid = 16135699 | doi = 10.1124/jpet.105.092155 | s2cid = 2247093 }}</ref> |
|
|
|- |
|
|
| ] || 31–38 || Antagonist || <ref name="pmid8935801">{{cite journal | vauthors = Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE | title = Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding | journal = Psychopharmacology | volume = 124 | issue = 1–2 | pages = 57–73 | date = March 1996 | pmid = 8935801 | doi = 10.1007/bf02245606 | s2cid = 12028979 }}</ref><ref name="pmid8997630">{{cite journal | vauthors = Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A | title = Iloperidone binding to human and rat dopamine and 5-HT receptors | journal = European Journal of Pharmacology | volume = 317 | issue = 2–3 | pages = 417–423 | date = December 1996 | pmid = 8997630 | doi = 10.1016/s0014-2999(96)00840-0 }}</ref> |
|
|
|- |
|
|
| ] || 21–52 || Antagonist || <ref name="pmid8935801" /><ref name="pmid8566176">{{cite journal | vauthors = Seeman P, Van Tol HH | title = Deriving the therapeutic concentrations for clozapine and haloperidol: the apparent dissociation constant of a neuroleptic at the dopamine D2 or D4 receptor varies with the affinity of the competing radioligand | journal = European Journal of Pharmacology | volume = 291 | issue = 2 | pages = 59–66 | date = October 1995 | pmid = 8566176 | doi = 10.1016/0922-4106(95)90125-6 }}</ref> |
|
|
|- |
|
|
| ] || 7.8–91 || Antagonist || <ref name="pmid9577836" /><ref name="pmid16135699" /> |
|
|
|- |
|
|
| ] || 1.6–50 || Antagonist || <ref name="pmid9577836" /><ref name="pmid18595716">{{cite journal | vauthors = Ablordeppey SY, Altundas R, Bricker B, Zhu XY, Kumar EV, Jackson T, Khan A, Roth BL | title = Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4--1-(4-fluorophenyl)butan-1-one | journal = Bioorganic & Medicinal Chemistry | volume = 16 | issue = 15 | pages = 7291–7301 | date = August 2008 | pmid = 18595716 | pmc = 2664318 | doi = 10.1016/j.bmc.2008.06.030 }}</ref> |
|
|
|- |
|
|
| ] || 17–102 || Antagonist || <ref name="pmid9430133">{{cite journal | vauthors = Arnt J, Skarsfeldt T | title = Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence | journal = Neuropsychopharmacology | volume = 18 | issue = 2 | pages = 63–101 | date = February 1998 | pmid = 9430133 | doi = 10.1016/S0893-133X(97)00112-7 | doi-access = free }}</ref><ref name="pmid9262370">{{cite journal | vauthors = Tallman JF, Primus RJ, Brodbeck R, Cornfield L, Meade R, Woodruff K, Ross P, Thurkauf A, Gallager DW | title = I. NGD 94-1: identification of a novel, high-affinity antagonist at the human dopamine D4 receptor | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 282 | issue = 2 | pages = 1011–1019 | date = August 1997 | pmid = 9262370 }}</ref> |
|
|
|- |
|
|
| ] || 21–60 || Antagonist || <ref name="pmid8566176" /> |
|
|
|- |
|
|
| ] || 74–90 || Antagonist || <ref name="PDSP" /><ref name="pmid8997630" /> |
|
|
|- |
|
|
| ] || 0.65–4.9 || Inverse agonist || <ref name="PDSP" /><ref name="pmid8935801" /> |
|
|
|- |
|
|
| ] || 44 || Antagonist || <ref name="PDSP" /> |
|
|
|- |
|
|
| ] || 3,713 || Antagonist || <ref name="PDSP" /> |
|
|
|- |
|
|
| ] || >10,000 || Antagonist || <ref name="PDSP" /> |
|
|
|- |
|
|
| ] || 2.5–73 || Antagonist || <ref name="pmid8822531">{{cite journal | vauthors = Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT | title = Radioreceptor binding profile of the atypical antipsychotic olanzapine | journal = Neuropsychopharmacology | volume = 14 | issue = 2 | pages = 87–96 | date = February 1996 | pmid = 8822531 | doi = 10.1016/0893-133X(94)00129-N | doi-access = free }}</ref><ref name="pmid10708730">{{cite journal | vauthors = Bymaster FP, Falcone JF | title = Decreased binding affinity of olanzapine and clozapine for human muscarinic receptors in intact clonal cells in physiological medium | journal = European Journal of Pharmacology | volume = 390 | issue = 3 | pages = 245–248 | date = March 2000 | pmid = 10708730 | doi = 10.1016/s0014-2999(00)00037-6 }}</ref> |
|
|
|- |
|
|
| ] || 48–622 || Antagonist || <ref name="pmid14642972" /> |
|
|
|- |
|
|
| ] || 13–126 || Antagonist || <ref name="pmid10227113" /><ref name="pmid14642972" /> |
|
|
|- |
|
|
| ] || 10–350 || Antagonist || <ref name="pmid14642972" /><ref name="pmid8822531" /> |
|
|
|- |
|
|
| ] || 6.0–82 || Antagonist || <ref name="pmid14642972" /><ref name="pmid8822531" /> |
|
|
|- |
|
|
| ] || >5,000 || {{abbr|ND|No data}} || <ref name="pmid8935801" /> |
|
|
|- |
|
|
| ] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} |
|
|
|- |
|
|
| ] || >10,000 || {{abbr|ND|No data}} || <ref name="pmid8935801" /> |
|
|
|- |
|
|
| {{abbrlink|nACh|Nicotinic acetylcholine receptor}} || >10,000 || {{abbr|ND|No data}} || <ref name="PDSP" /> |
|
|
|- |
|
|
| ] || >10,000 || {{abbr|ND|No data}} || <ref name="PDSP" /> |
|
|
|- |
|
|
| {{abbrlink|VDCC|Voltage-dependent calcium channel}} || >10,000 || {{abbr|ND|No data}} || <ref name="PDSP" /><ref name="pmid8935801" /> |
|
|
|- |
|
|
| {{abbrlink|VGSC|Voltage-gated sodium channel}} || >5,000 || {{abbr|ND|No data}} || <ref name="pmid8935801" /> |
|
|
|- |
|
|
| {{abbrlink|hERG|Human Ether-à-go-go-Related Gene}} || 6,013 || Blocker || <ref name="pmid12176106">{{cite journal | vauthors = Kongsamut S, Kang J, Chen XL, Roehr J, Rampe D | title = A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs | journal = European Journal of Pharmacology | volume = 450 | issue = 1 | pages = 37–41 | date = August 2002 | pmid = 12176106 | doi = 10.1016/s0014-2999(02)02074-5 }}</ref> |
|
|
|- class="sortbottom" |
|
|
| colspan="5" style="width: 1px;" | Values are K<sub>i</sub> (nM). The smaller the value, the more strongly the drug binds to the site. All data are for human cloned proteins, except H<sub>3</sub> (guinea pig), σ<sub>1</sub> (guinea pig), opioid (rodent), {{abbr|NMDA|N-Methyl-D-aspartate receptor}}/{{abbr|PCP|Phencyclidine site}} (rat), {{abbr|VDCC|Voltage-dependent calcium channel}}, and {{abbr|VGSC|Voltage-gated calcium channel}}.<ref name="PDSP" /> |
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|} |
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|
Olanzapine was first discovered while searching for a chemical analog of ] that would not require hematological monitoring. Investigation on a series of thiophene isosteres on 1 of the phenyl rings in clozapine, a ] analog (olanzapine) was discovered.<ref name="Citrome_2019">{{cite journal | vauthors = Citrome L, McEvoy JP, Todtenkopf MS, McDonnell D, Weiden PJ | title = A commentary on the efficacy of olanzapine for the treatment of schizophrenia: the past, present, and future | journal = Neuropsychiatric Disease and Treatment | volume = 15 | pages = 2559–2569 | date = September 2019 | pmid = 31564881 | pmc = 6733343 | doi = 10.2147/NDT.S209284 | doi-access = free }}</ref> |
|
On January 15, 2009 Eli Lilly plead guilty to a misdemeanor charge of illegally marketing Zyprexa for off-label use, and agreed to pay $1.4 billion.<ref> Lilly settles Zyprexa suit for $1.42 billion. The Associated Press, January 15, 2009</ref> Although Lilly had evidence that it is not effective for ], Zyprexa was marketed for elderly ] patients.<ref>{{cite news|author=Cronin Fisk, Martha, Lopatto, Elizabeth and Feeley, Jef|title=Lilly Sold Drug for Dementia Knowing It Didn’t Help, Files Show|url=http://www.bloomberg.com/apps/news?pid=20601109&sid=aTLcF3zT1Pdo|date=June 1, 2009|publisher=Bloomberg L.P.|accessdate=2009-09-03}}</ref> The drug carries an F.D.A. warning that it increases the risk of death in older patients with dementia-related psychosis.<ref>{{cite news|author=Berenson, Alex|title=Drug Files Show Maker Promoted Unapproved Use |url=http://www.nytimes.com/2006/12/18/business/18drug.ht|date=December 18, 2006|publisher=The New York Times|accessdate=2009-09-03}}</ref> |
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Olanzapine has a higher affinity for ] than ] receptors, which is a common property of most atypical antipsychotics, aside from the benzamide antipsychotics such as ] along with the nonbenzamides ], ], ], ], ], and ]. |
|
In order to make up for the costs for settling the lawsuits and shrinking sales figures for Zyprexa in the U.S.A. the company increased the prices for this medication in Germany in May 2007 by 18 percent. |
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|
<ref>, Tödliche Nebenwirkungen? - |
|
|
Umstrittenes Medikament bringt satte Gewinne</ref><ref>, Zyprexa - Umstrittenes Medikament bringt satte Gewinne</ref> |
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In one study ] occupancy was 60% with low-dose olanzapine (5 mg/day) and occupancy with high dose at 83% (20 mg/day).<ref>{{Cite web |title=NEJM Journal Watch: Summaries of and commentary on original medical and scientific articles from key medical journals |url=https://www.jwatch.org/jp199910010000012/1999/10/01/dopamine-d2-receptor-occupancy-olanzapine |access-date=27 November 2022 |website=www.jwatch.org}}</ref> In the usual clinical dose range of 10–20 mg/day, ] occupancy varied from 71% to 80%.<ref>{{cite journal | vauthors = Kapur S, Zipursky RB, Remington G, Jones C, DaSilva J, Wilson AA, Houle S | title = 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation | journal = The American Journal of Psychiatry | volume = 155 | issue = 7 | pages = 921–928 | date = July 1998 | pmid = 9659858 | doi = 10.1176/ajp.155.7.921 | s2cid = 23678989 }}</ref> |
|
==Chemistry== |
|
|
http://www.google.com/patents/about?id=ZGYeAAAAEBAJ&dq=US+5229382 |
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] |
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Olanzapine occupancy at ] receptor are high at all doses (5 mg to 20 mg). It is reported that 5 mg dose of olanzapine produced a mean occupancy of 85% at 5 mg, 88% at 10 mg, and 93% at 20 mg dose .<ref>{{cite journal | vauthors = Kessler RM, Ansari MS, Riccardi P, Li R, Jayathilake K, Dawant B, Meltzer HY | title = Occupancy of striatal and extrastriatal dopamine D2/D3 receptors by olanzapine and haloperidol | journal = Neuropsychopharmacology | volume = 30 | issue = 12 | pages = 2283–2289 | date = December 2005 | pmid = 16123775 | doi = 10.1038/sj.npp.1300836 | s2cid = 19688114 | doi-access = free }}</ref> |
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==See also== |
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*] |
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*] |
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Olanzapine had the highest affinity of any second-generation antipsychotic towards the ] in one ''in vitro'' study.<ref>{{cite journal | vauthors = Wang JS, Zhu HJ, Markowitz JS, Donovan JL, DeVane CL | title = Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein | journal = Psychopharmacology | volume = 187 | issue = 4 | pages = 415–423 | date = September 2006 | pmid = 16810505 | doi = 10.1007/s00213-006-0437-9 | s2cid = 13365903 }}</ref> P-glycoprotein transports a myriad of drugs across a number of different biological membranes (found in numerous body systems) including the ] (a semipermeable membrane that filters the contents of blood prior to it reaching the brain); P-GP inhibition could mean that less brain exposure to olanzapine results from this interaction with the P-glycoprotein.<ref>{{cite journal | vauthors = Moons T, de Roo M, Claes S, Dom G | title = Relationship between P-glycoprotein and second-generation antipsychotics | journal = Pharmacogenomics | volume = 12 | issue = 8 | pages = 1193–1211 | date = August 2011 | pmid = 21843066 | doi = 10.2217/pgs.11.55 }}</ref> A relatively large quantity of commonly encountered foods and medications inhibit P-GP, and pharmaceuticals fairly commonly are either substrates of P-GP or inhibit its action; both substrates and inhibitors of P-GP effectively increase the permeability of the blood-brain barrier to P-GP substrates and subsequently increase the central activity of the substrate, while reducing the local effects on the GI tract. The mediation of olanzapine in the central nervous system by P-GP means that any other substance or drug that interacts with P-GP increases the risk for toxic accumulations of both olanzapine and the other drug.<ref>{{cite journal|title=Drug Transporters: The Final Frontier for Drug Interactions|date=1 December 2008|vauthors=Horn JR, Hansten P|url=http://www.pharmacytimes.com/publications/issue/2008/2008-12/2008-12-8474|journal=Pharmacy Times|access-date=9 February 2017|archive-date=11 February 2017|archive-url=https://web.archive.org/web/20170211080820/http://www.pharmacytimes.com/publications/issue/2008/2008-12/2008-12-8474|url-status=dead}}</ref> |
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==Notes and references== |
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{{Reflist|2}} |
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Olanzapine is a potent antagonist of the muscarinic M<sub>3</sub> receptor,<ref>{{cite journal | vauthors = Johnson DE, Yamazaki H, Ward KM, Schmidt AW, Lebel WS, Treadway JL, Gibbs EM, Zawalich WS, Rollema H | title = Inhibitory effects of antipsychotics on carbachol-enhanced insulin secretion from perifused rat islets: role of muscarinic antagonism in antipsychotic-induced diabetes and hyperglycemia | journal = Diabetes | volume = 54 | issue = 5 | pages = 1552–1558 | date = May 2005 | pmid = 15855345 | doi = 10.2337/diabetes.54.5.1552 | doi-access = free }}</ref> which may underlie its diabetogenic side effects.<ref name="Weston-Green 1069–1080">{{cite journal | vauthors = Weston-Green K, Huang XF, Deng C | title = Second generation antipsychotic-induced type 2 diabetes: a role for the muscarinic M3 receptor | journal = CNS Drugs | volume = 27 | issue = 12 | pages = 1069–1080 | date = December 2013 | pmid = 24114586 | doi = 10.1007/s40263-013-0115-5 | s2cid = 5133679 }}</ref><ref>{{cite journal | vauthors = Silvestre JS, Prous J | title = Research on adverse drug events. I. Muscarinic M3 receptor binding affinity could predict the risk of antipsychotics to induce type 2 diabetes | journal = Methods and Findings in Experimental and Clinical Pharmacology | volume = 27 | issue = 5 | pages = 289–304 | date = June 2005 | pmid = 16082416 | doi = 10.1358/mf.2005.27.5.908643 }}</ref> |
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==External links== |
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Additionally, it also exhibits a relatively low affinity for serotonin 5-HT<sub>1</sub>, GABA<sub>A</sub>, β-adrenergic receptors, and ] binding sites.<ref name="lexicomp"/><ref>{{cite web|url=http://www.cancer.gov/Templates/drugdictionary.aspx?&cdrid=449664&page=1&print=1 |title=olanzapine |publisher=National Cancer Institute |work=NCI Drug Dictionary|date=2 February 2011 }}</ref> |
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===Manufacturer site=== |
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* - official Zyprexa brand website from ] |
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* |
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Although antagonistic effects of olanzapine at 5-HT<sub>2C</sub> alone are not associated with weight gain, olanzapine antagonism at histaminergic H<sub>1</sub>, and muscarinic M<sub>3</sub> receptors have been implicated in weight gain.<ref name="Citrome_2019" /><ref>{{cite journal | vauthors = Van Oekelen D, Luyten WH, Leysen JE | title = 5-HT2A and 5-HT2C receptors and their atypical regulation properties | journal = Life Sciences | volume = 72 | issue = 22 | pages = 2429–2449 | date = April 2003 | pmid = 12650852 | doi = 10.1016/s0024-3205(03)00141-3 }}</ref><ref>{{cite journal | vauthors = Reynolds GP, Hill MJ, Kirk SL | title = The 5-HT2C receptor and antipsychotic-induced weight gain - mechanisms and genetics | journal = Journal of Psychopharmacology | volume = 20 | issue = 4 Suppl | pages = 15–18 | date = July 2006 | pmid = 16785265 | doi = 10.1177/1359786806066040 | s2cid = 19934754 }}</ref> |
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===Consumer information=== |
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|
* - 'Information on Zyprexa and How to Use It, Precautions and Other Medications to Avoid While Taking, ] |
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* - 'Olanzapine (Systemic)' Drug Information, ] |
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The mode of action of olanzapine's antipsychotic activity is unknown. It may involve antagonism of ] and ] receptors. Antagonism of dopamine receptors is associated with ] such as ] (TD), and with therapeutic effects. Antagonism of ] is associated with ] side effects such as dry mouth and constipation; in addition, it may suppress or reduce the emergence of extrapyramidal effects for the duration of treatment, but it offers no protection against the development of TD. In common with other second-generation (atypical) antipsychotics, olanzapine poses a relatively low risk of extrapyramidal side effects including TD, due to its higher affinity for the 5HT<sub>2A</sub> receptor over the D<sub>2</sub> receptor.<ref name="foyes">{{cite book | vauthors = Lemke TL, Williams DA | date = 2009 | title = Foye's Medicinal Chemistry | edition = 6th | publisher = Wolters Kluwer | location = New Delhi | isbn = 978-81-89960-30-8 }}</ref> |
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===Controversy=== |
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* - Lilly Settles With 18,000 Over Zyprexa, Alex Berenson, '']'' (December 17, 2006) |
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Antagonizing H<sub>1</sub> histamine receptors causes sedation and may cause weight gain, although antagonistic actions at serotonin 5-HT<sub>2C</sub> and dopamine D<sub>2</sub> receptors have also been associated with weight gain and appetite stimulation.<ref>{{cite journal | vauthors = Wallace TJ, Zai CC, Brandl EJ, Müller DJ | title = Role of 5-HT(2C) receptor gene variants in antipsychotic-induced weight gain | journal = Pharmacogenomics and Personalized Medicine | volume = 4 | pages = 83–93 | date = 18 August 2011 | pmid = 23226055 | pmc = 3513221 | doi = 10.2147/PGPM.S11866 | doi-access = free }}</ref> |
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===Pharmacokinetics=== |
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====Metabolism==== |
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Olanzapine is metabolized by the ] (CYP) system; principally by isozyme 1A2 (CYP1A2) and to a lesser extent by CYP2D6. By these mechanisms, more than 40% of the oral dose, on average, is removed by the ].<ref name="lexicomp"/> ] of olanzapine appears to vary by sex; women have roughly 25% lower clearance than men.<ref name="Schwenger Review">{{cite journal | vauthors = Schwenger E, Dumontet J, Ensom MH | title = Does olanzapine warrant clinical pharmacokinetic monitoring in schizophrenia? | journal = Clinical Pharmacokinetics | volume = 50 | issue = 7 | pages = 415–428 | date = July 2011 | pmid = 21651311 | doi = 10.2165/11587240-000000000-00000 | s2cid = 21097041 }}</ref> Clearance of olanzapine also varies by race; in self-identified African Americans or Blacks, olanzapine's clearance was 26% higher.<ref name="Schwenger Review" /> A difference in the clearance is not apparent between individuals identifying as Caucasian, Chinese, or Japanese.<ref name="Schwenger Review" /> Routine, pharmacokinetic monitoring of olanzapine plasma levels is generally unwarranted, though unusual circumstances (e.g. the presence of drug-drug interactions) or a desire to determine if patients are taking their medicine may prompt its use.<ref name="Schwenger Review" /> |
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====Chemistry==== |
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Olanzapine is unusual in having four well-characterised crystalline ] and many hydrated forms.<ref>{{cite journal | vauthors = Reutzel-Edens SM, Bhardwaj RM | title = Crystal forms in pharmaceutical applications: olanzapine, a gift to crystal chemistry that keeps on giving | journal = IUCrJ | volume = 7 | issue = Pt 6 | pages = 955–964 | date = November 2020 | pmid = 33209310 | pmc = 7642794 | doi = 10.1107/S2052252520012683 | bibcode = 2020IUCrJ...7..955R }}</ref> |
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==Chemical synthesis== |
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The preparation of olanzapine was first disclosed in a series of patents from ] in the 1990s. In the final two steps, -3-thiophenecarbonitrile]] was reduced with ] in ] to give the substituted ] ring system, and this was treated with ] in a mixture of dimethyl sulfoxide and toluene as solvent to produce the drug.<ref>{{cite patent |country=US |number=5817655|status=patent |gdate=1998-10-06 |fdate=1996-11-13 |pridate=1991-04-23 | inventor = Chakrabarti JK, Hotten TM, Tupper DE |title=Methods of treatment using a thieno-benzodiazepine |assign1=Eli Lilly and Co Ltd.}}</ref> |
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:] |
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==Society and culture== |
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])]] |
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===Legal status=== |
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Olanzapine is approved by the US FDA for: |
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* Treatment—in combination with fluoxetine—of depressive episodes associated with bipolar disorder (December 2003).<ref> |
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{{cite web| title = NDA 21–520| publisher = Food and Drug Administration| date = 24 December 2003| url = http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2003/21520ltr.pdf| access-date = 6 September 2009}}</ref> |
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* Long-term treatment of ] (January 2004).<ref> |
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{{cite web| title = NDA 20-592 / S-019| publisher = Food and Drug Administration| date = 14 January 2004| url = http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/20592se1-019ltr.pdf| access-date = 6 September 2009}}</ref><ref>{{cite journal | vauthors = Pillarella J, Higashi A, Alexander GC, Conti R | title = Trends in use of second-generation antipsychotics for treatment of bipolar disorder in the United States, 1998-2009 | journal = Psychiatric Services | volume = 63 | issue = 1 | pages = 83–86 | date = January 2012 | pmid = 22227765 | pmc = 4594841 | doi = 10.1176/appi.ps.201100092 }}</ref> |
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* Long-term treatment—in combination with fluoxetine—of resistant depression (March 2009)<ref name="pmid19590732">{{cite journal | vauthors = Bobo WV, Shelton RC | title = Olanzapine and fluoxetine combination therapy for treatment-resistant depression: review of efficacy, safety, and study design issues | journal = Neuropsychiatric Disease and Treatment | volume = 5 | pages = 369–383 | date = 2009 | pmid = 19590732 | pmc = 2706569 | doi = 10.2147/NDT.S5819 | doi-access = free }}</ref> |
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* Oral formulation: acute and maintenance treatment of schizophrenia in adults, acute treatment of manic or mixed episodes associated with bipolar I disorder (monotherapy and in combination with ] or ]) |
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* Intramuscular formulation: acute agitation associated with schizophrenia and bipolar I mania in adults |
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* Oral formulation combined with fluoxetine: treatment of acute depressive episodes associated with bipolar I disorder in adults, or treatment of acute, resistant depression in adults<ref>treatment resistant depression defined as major depressive disorder in adult patients who do not respond to two separate trials of different antidepressants of adequate dose and duration in the current episode</ref> |
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* Treatment of the manifestations of psychotic disorders (September 1996<ref name="NDA 20-592"> |
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{{cite web| title = NDA 20-592| publisher = Food and Drug Administration| date = 6 September 1996| url = http://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf| access-date = 6 September 2009}}</ref> – March 2000).<ref name="Off-label"> |
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{{cite web| title = Eli Lilly and Company Agrees to Pay $1.415 Billion to Resolve Allegations of Off-label Promotion of Zyprexa| publisher = U.S. Justice Department| date = 15 January 2009| url = http://www.justice.gov/opa/pr/2009/January/09-civ-038.html| access-date = 9 July 2012}}</ref> |
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* Short-term treatment of acute manic episodes associated with bipolar I disorder (March 2000)<ref name="Off-label" /> |
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* Short-term treatment of schizophrenia instead of the management of the manifestations of psychotic disorders (March 2000)<ref name="Off-label" /> |
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* Maintaining treatment response in schizophrenic patients who had been stable for about eight weeks and were then followed for a period of up to eight months (November 2000)<ref name="Off-label" /> |
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The drug became ] in 2011. Sales of Zyprexa in 2008 were $2.2 billion in the US and $4.7 billion worldwide.<ref>{{cite web| title = Lilly 2008 Annual Report| publisher = Lilly| year = 2009| url = http://files.shareholder.com/downloads/LLY/696621960x0x296463/611E167A-61C9-4C03-8866-ACF5FA7C8953/English.PDF| access-date = 6 August 2009| archive-url = https://web.archive.org/web/20111001135218/http://files.shareholder.com/downloads/LLY/696621960x0x296463/611E167A-61C9-4C03-8866-ACF5FA7C8953/English.PDF| archive-date = 1 October 2011|url-status = dead}}</ref> |
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===Controversy and litigation=== |
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] has faced many lawsuits from people who claimed they developed diabetes or other diseases after taking Zyprexa, as well as by various governmental entities, insurance companies, and others. Lilly produced a large number of documents as part of the ] of this litigation, which started in 2004; the documents were ruled to be confidential by a judge and placed under ], and later themselves became the subject of litigation.<ref name=NYTrelease/> |
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In 2006, Lilly paid $700 million to settle around 8,000 of these lawsuits,<ref>{{cite news | vauthors = Berenson A |url=https://www.nytimes.com/2007/01/04/business/04drug.html |title=Mother Wonders if Psychosis Drug Helped Kill Son |work=The New York Times |date=4 January 2007 |access-date=21 May 2013}}</ref> and in early 2007, Lilly settled around 18,000 suits for $500 million, which brought the total Lilly had paid to settle suits related to the drug to $1.2 billion.<ref name=NYT200101>{{cite news | vauthors = Berenson A |title=Lilly Settles With 18,000 Over Zyprexa|url=https://www.nytimes.com/2007/01/05/business/05drug.html?_r=0|work=The New York Times|date=5 January 2007}}</ref><ref name=timeso/> |
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A December 2006 '']'' article based on leaked company documents concluded that the company had engaged in a deliberate effort to downplay olanzapine's side effects.<ref name=NYT200101/><ref>{{cite news| vauthors = Berenson A |title=Eli Lilly Said to Play Down Risk of Top Pill |url=https://www.nytimes.com/2006/12/17/business/17drug.html|work=The New York Times |date=17 December 2006 |access-date=21 May 2013}}</ref> The company denied these allegations and stated that the article had been based on cherry-picked documents.<ref name=NYT200101/><ref name=timeso/> The documents were provided to the ''Times'' by ], a lawyer who represented mentally ill patients, who obtained them from a doctor, David Egilman, who was serving as an expert consultant on the case.<ref name=NYTrelease/> After the documents were leaked to online peer-to-peer, file-sharing networks by ] and others in the ], who obtained copies,<ref>{{cite news| vauthors = Ashton K |title=Activist Gagged for Drug Fact Leak in Lily Case|url=http://www.freedom-center.org/pdf/1-16-07ActivistGaggedLillyWillHallGazetteSCANNED.pdf|work=Hampshire Daily Gazette|date=16 January 2007}}</ref> in 2007 Lilly filed a protection order to stop the dissemination of some of the documents, which Judge ] of the Brooklyn Federal District Court granted. Judge Weinstein also criticized the ''New York Times'' reporter, Gottstein, and Egilman in the ruling.<ref name=NYTrelease/> '']'' of London also received the documents and reported that as early as 1998, Lilly considered the risk of drug-induced obesity to be a "top threat" to Zyprexa sales.<ref name=timeso>{{cite news| vauthors = Pagnamenta R |title=Eli Lilly was concerned by Zyprexa side-effects from 1998 |url= http://www.timesonline.co.uk/tol/life_and_style/health/article1295456.ece |work=The Times (London)|date=23 January 2007 |archive-url=https://web.archive.org/web/20070220232729/http://www.timesonline.co.uk/tol/life_and_style/health/article1295456.ece|archive-date=20 February 2007}}</ref> On 9 October 2000, senior Lilly research physician Robert Baker noted that an academic advisory board to which he belonged was "quite impressed by the magnitude of weight gain on olanzapine and implications for glucose."<ref name=timeso/> |
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Lilly had threatened Egilman with criminal contempt charges regarding the documents he took and provided to reporters; in September 2007, he agreed to pay Lilly $100,000 in return for the company's agreement to drop the threat of charges.<ref name=NYT2009-01>{{cite news | vauthors = Harris G, Berenson A |title=Lilly Said to Be Near $1.4 Billion U.S. Settlement |url=https://www.nytimes.com/2009/01/15/business/15drug.html|work=The New York Times|date=14 January 2009}}</ref> |
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In September 2008, Judge Weinstein issued an order to make public Lilly's internal documents about the drug in a different suit brought by insurance companies, pension funds, and other payors.<ref name=NYTrelease>{{cite news| vauthors = Walsh MW |title=Judge to Unseal Documents on the Eli Lilly Drug Zyprexa |url= https://www.nytimes.com/2008/09/06/business/06lilly.html |work=The New York Times |date=5 September 2008}}</ref> |
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In March 2008, Lilly settled a suit with the state of Alaska,<ref>{{cite news| vauthors = Berenson A |title=Lilly Settles Alaska Suit Over Zyprexa|url=https://www.nytimes.com/2008/03/26/business/26cnd-zyprexa.html|work=The New York Times|date=26 March 2008}}</ref> and in October 2008, Lilly agreed to pay $62 million to 32 states and the District of Columbia to settle suits brought under state ] laws.<ref name=NYT2009-01/> |
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In 2009, Eli Lilly pleaded guilty to a US federal criminal ] charge of illegally marketing Zyprexa for ] and agreed to pay $1.4 billion. The settlement announcement stated "Eli Lilly admits that between September 1999 and March 31, 2001, the company promoted Zyprexa in elderly populations as a treatment for dementia, including Alzheimer's dementia. Eli Lilly has agreed to pay a $515 million criminal fine and to forfeit an additional $100 million in assets."<ref name="MSN.com">{{cite web |title=Lilly settles Zyprexa suit for $1.42 billion |url=https://www.nbcnews.com/health/health-news/eli-lilly-settles-zyprexa-lawsuit-1-42-billion-flna1C9453543 |website=NBCNews.com |publisher=Associated Press |url-status=live |archive-url=https://web.archive.org/web/20210131221349/https://www.nbcnews.com/health/health-news/eli-lilly-settles-zyprexa-lawsuit-1-42-billion-flna1C9453543 |archive-date=31 January 2021 |date=15 January 2009}}</ref><ref name="Berenson, Alex">{{cite news | vauthors = Berenson A |title=Drug Files Show Maker Promoted Unapproved Use |url=https://www.nytimes.com/2006/12/18/business/18drug.html |date=18 December 2006 |work=The New York Times|access-date=21 May 2013}}</ref> |
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The outcomes described here, and their legal ramifications, were fueled by motions and appeals that were not resolved until 2010.<ref>{{cite book |last1=PsychRights |title=Law Project for Psychiatric Rights: Summary and Links to Relevant Documents in the Zyprexa Scandal |year=2010 |publisher=PsychRights | url = http://psychrights.org/States/Alaska | access-date = 26 October 2021 }}</ref> In 2021, Gottstein summarized this tangle of legal activities, and their impact on the political landscape of psychiatry and antipsychiatry in the US, in ''The Zyprexa Papers''.<ref>{{cite book | vauthors = Gottstein J |title=The Zyreza Papers |year= 2021 |publisher=Samizdat Health Writer's Cooperative 2021 | url = https://thezyprexapapers.com/ | access-date = 26 October 2021 }}</ref> |
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===Brand names=== |
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Olanzapine is generic and available under many brand names worldwide.<ref name=Drugnames>{{cite web | work = Drugs.com | url = https://www.drugs.com/international/olanzapine.html | title = Drugs.com international listings for Olanzapine | access-date = 4 August 2015 }}</ref> |
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{| class="wikitable mw-collapsible mw-collapsed" style="width:100%" |
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|+ List of ]s for olanzapine<ref name=Drugnames/> |
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|A||Aedon, Alonzap, Amulsin, Anzap, Anzatric, Anzorin, Apisco, Apo-Olanzapine, Apo-Olanzapine ODT, Apsico, Arenbil, Arkolamyl |
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|B||Benexafrina, Bloonis |
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|C||Caprilon, Cap-Tiva, Clingozan |
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|D||Deprex, Domus, Dopin |
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|E||Egolanza, Elynza, Emzypine, Epilanz-10, Exzapine |
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|F||Fontanivio, Fordep |
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|G|| |
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|H|| |
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|I||Irropia |
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|J||Jolyon-MD |
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|K||Kozylex |
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|L||Lanopin, Lanzapine, Lanzep, Lapenza, Lapozan, Lazap, Lazapir, Lazapix, Lezapin-MD, Lopez |
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|M||Meflax, Midax, Medizapin |
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|N||Niolib, Norpen Oro, Nykob, Nyzol |
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|O||Oferta, Oferta-Sanovel, Olace, Oladay, Oladay-F, Olaffar, Olan, Olanap, Olancell, Olandix, Olandoz, Olandus, Olankline, Olanpax, Olanstad, Olanza, Olanza Actavis, Olanza Actavis ODT, Olanzalet, Olanzalux, Olanzamed, Olanzapin 1A Pharma, Olanzapin AbZ, Olanzapin Accord, Olanzapin Actavis, Olanzapin AL, Olanzapin Apotex, Olanzapin Aristo, Olanzapin axcount, Olanzapin beta, Olanzapin Bluefish, Olanzapin Cipla, Olanzapin easypharm, Olanzapin Egis, Olanzapin G.L., Olanzapin Genera, Olanzapin Genericon, Olanzapin Helvepharm, Olanzapin Hennig, Olanzapin Heumann, Olanzapin HEXAL, Olanzapin Krka, Olanzapin Lilly, Olanzapin Mylan, Olanzapin Niolib, Olanzapin Orion, Olanzapin PCD, Olanzapin PharmaS, Olanzapin Ranbaxy, Olanzapin ratiopharm, Olanzapin ReplekFarm, Olanzapin Rth, Olanzapin Sandoz, Olanzapin Spirig HC, Olanzapin Stada, Olanzapin SUN, Olanzapin Teva, Olanzapin Viketo, Olanzapin Zentiva, Olanzapina Accord, Olanzapina Actavis, Olanzapina Actavis PTC, Olanzapina Aldal, Olanzapina Almus, Olanzapina Alter, Olanzapina Angenerico, Olanzapina Anipaz, Olanzapina Apotex, Olanzapina APS, Olanzapina Arrowblue, Olanzapina Aspen, Olanzapina Aurobindo, Olanzapina Basi, Olanzapina Bexalabs, Olanzapina Blixie, Olanzapina Bluefish, Olanzapina Bluepharma, Olanzapina Cantabria, Olanzapina Ceapharma, Olanzapina Ciclum, Olanzapina Cinfa, Olanzapina Cipla, Olanzapina Combix, Olanzapina Doc Generici, Olanzapina Dr. Reddy's, Olanzapina Eulex, Olanzapina Eurogenerici, Olanzapina Fantex, Olanzapina Farmoz, Olanzapina Flas Pharma Combix, Olanzapina Genedec, Olanzapina Generis, Olanzapina Germed, Olanzapina Glenmark, Olanzapina Green Avet, Olanzapina Helm, Olanzapina Kern Pharma, Olanzapina Krka, Olanzapina La Santé, Olanzapina Labesfal, Olanzapina Leugim, Olanzapina Lilly, Olanzapina LPH, Olanzapina Mabo, Olanzapina Medana, Olanzapina Medis, Olanzapina Medley, Olanzapina Mylan, Olanzapina Nakozap, Olanzapina Nolian, Olanzapina Normon, Olanzapina Ozilormar, Olanzapina Parke-Davis, Olanzapina Pensa, Olanzapina Pensa Pharma, Olanzapina Pharmakern, Olanzapina Polipharma, Olanzapina Polpharma, Olanzapina Qualigen, Olanzapina Ranbaxy, Olanzapina Ratio, Olanzapina Ratiopharm, Olanzapina Reconir, Olanzapina Reddy, Olanzapina Rospaw, Olanzapina Sabacur, Olanzapina Sandoz, Olanzapina Sarb, Olanzapina Stada, Olanzapina Sun, Olanzapina TAD, Olanzapina Technigen, Olanzapina Terapia, Olanzapina Teva, Olanzapina Tevagen, Olanzapina tolife, Olanzapina Torrent, Olanzapina Vegal, Olanzapina Vida, Olanzapina Winthrop, Olanzapina Wynn, Olanzapina Kraz, Olanzapina Zentiva, Olanzapina Zerpi, Olanzapina Zonapir, Olanzapin-Actavis, Olanzapin-CT, Olanzapine 1A Pharma, Olanzapine Accord, Olanzapine Actavis, Olanzapine Adamed, Olanzapine Alter, Olanzapine Alvogen, Olanzapine Apotex, Olanzapine Arrow Génériques, Olanzapine Auro, Olanzapine Aurobindo, Olanzapine Biogaran, Olanzapine Bluefish, Olanzapine CF, Olanzapine Clonmel, Olanzapine Cristers, Olanzapine Dexcel, Olanzapine EG, Olanzapine Egis, Olanzapine Evolugen, Olanzapine Galenicum, Olanzapine Generichealth, Olanzapine Glenmark, Olanzapine GSK, Olanzapine Isomed, Olanzapine Jacobsen, Olanzapine Jubilant, Olanzapine Lekam, Olanzapine Lesvi, Olanzapine Medana, Olanzapine Mylan, Olanzapine Neopharma, Olanzapine Niolib, Olanzapine Nyzol, Olanzapine Odis Mylan, Olanzapine ODT Generichealth, Olanzapine ODT Sanis Health, Olanzapine ODT Teva, Olanzapine ODT-DRLA, Olanzapine Orion, Olanzapine Polpharma, Olanzapine Prasco, Olanzapine Ranbaxy, Olanzapine Ratiopharm, Olanzapine Sandoz, Olanzapine Sanis Health, Olanzapine Sanovel, Olanzapine Stada, Olanzapine Sun, Olanzapine Synthon, Olanzapine Teva, Olanzapine Torrent, Olanzapine Zentiva, Olanzapine Zentiva Lab, Olanzapine Zydus, Olanzapine-DRLA, Olzapine, Olanzia |
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|P|| Pinaz |
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|X|| |
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|Y|| |
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|Z||Zyprexa, Zolafren, Zalasta, Zypine |
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===Dosage forms=== |
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Olanzapine is marketed in many countries, with tablets ranging from 2.5 to 20 mg. Zyprexa (and generic olanzapine) is available as an orally disintegrating "wafer", which rapidly dissolves in saliva. It is also available in 10-mg vials for intramuscular injection.<ref name=olanzapinepi /> |
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==Research== |
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Olanzapine may be useful in promoting weight gain in underweight adult outpatients with ]. However, no improvement in psychological symptoms was noted.<ref>{{cite journal | vauthors = Attia E, Steinglass JE, Walsh BT, Wang Y, Wu P, Schreyer C, Wildes J, Yilmaz Z, Guarda AS, Kaplan AS, Marcus MD | title = Olanzapine Versus Placebo in Adult Outpatients With Anorexia Nervosa: A Randomized Clinical Trial | journal = The American Journal of Psychiatry | volume = 176 | issue = 6 | pages = 449–456 | date = June 2019 | pmid = 30654643 | pmc = 7015155 | doi = 10.1176/appi.ajp.2018.18101125 | doi-access = free }}</ref> It has also been shown to be helpful in the management of cancer-related anorexia.<ref>{{cite journal | vauthors = Sandhya L, Devi Sreenivasan N, Goenka L, Dubashi B, Kayal S, Solaiappan M, Govindarajalou R, Kt H, Ganesan P | title = Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer | journal = Journal of Clinical Oncology | volume = 41 | issue = 14 | pages = 2617–2627 | date = May 2023 | pmid = 36977285 | doi = 10.1200/JCO.22.01997 }}</ref> |
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Olanzapine has been shown to help address a range of anxiety and depressive symptoms in individuals with schizophrenia and schizoaffective disorders, and has since been used in the treatment of a range of mood and anxiety disorders.<ref>{{cite journal | vauthors = Hershenberg R, Gros DF, Brawman-Mintzer O | title = Role of atypical antipsychotics in the treatment of generalized anxiety disorder | journal = CNS Drugs | volume = 28 | issue = 6 | pages = 519–533 | date = June 2014 | pmid = 24794100 | doi = 10.1007/s40263-014-0162-6 | s2cid = 23429449 }}</ref> Olanzapine is no less effective than ] or ] and more effective than placebo in treating bipolar disorder.<ref>{{cite journal | vauthors = Narasimhan M, Bruce TO, Masand P | title = Review of olanzapine in the management of bipolar disorders | journal = Neuropsychiatric Disease and Treatment | volume = 3 | issue = 5 | pages = 579–587 | date = October 2007 | pmid = 19300587 | pmc = 2656294 }}</ref> It has also been used for ] and ].<ref>{{cite web | vauthors = Scott L |url=http://www.stutteringhelp.org/default.aspx?TabId=462 |publisher=Stuttering Foundation of America|title=Genetic and Neurological Factors in Stuttering |date=Winter 2006}}</ref> |
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Olanzapine has been studied for the treatment of hyperactivity, aggressive behavior, and repetitive behaviors in ].<ref>{{cite web |url=http://www.researchautism.net/interventions/102/olanzapine-and-autism?print=1 | title = Olanzapine and Autism |date=19 December 2017 | work = Research Autism | access-date = 9 June 2018 }}</ref> |
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Olanzapine is frequently prescribed off-label for the treatment of insomnia, including difficulty falling asleep and staying asleep, even though such use is not recommended.<ref>{{cite journal | vauthors = Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, Espie CA, Garcia-Borreguero D, Gjerstad M, Gonçalves M, Hertenstein E, Jansson-Fröjmark M, Jennum PJ, Leger D, Nissen C, Parrino L, Paunio T, Pevernagie D, Verbraecken J, Weeß HG, Wichniak A, Zavalko I, Arnardottir ES, Deleanu OC, Strazisar B, Zoetmulder M, Spiegelhalder K | title = European guideline for the diagnosis and treatment of insomnia | journal = Journal of Sleep Research | volume = 26 | issue = 6 | pages = 675–700 | date = December 2017 | pmid = 28875581 | doi = 10.1111/jsr.12594 | s2cid = 10136993 | doi-access = free }}</ref> The daytime sedation experienced with olanzapine is generally comparable to ] and ], which is a frequent complaint in clinical trials. In some cases, the sedation due to olanzapine impaired the ability of people to wake up at a consistent time every day. Some evidence of efficacy for treating insomnia is seen; however, side effects such as ] and ], which may be observed even at low doses, outweigh any potential benefits for insomnia that are not due to an underlying mental health condition.<ref name="Morin MHC">{{cite journal | vauthors = Morin AK | title = Off-label use of atypical antipsychotic agents for treatment of insomnia |journal=Mental Health Clinician |date=March 2014 |volume=4 |issue=2 |pages=65–72 |doi=10.9740/mhc.n190091 |doi-access=free }}</ref><ref>{{cite journal | vauthors = Yoshida K, Takeuchi H | title = Dose-dependent effects of antipsychotics on efficacy and adverse effects in schizophrenia | journal = Behavioural Brain Research | volume = 402 | pages = 113098 | date = March 2021 | pmid = 33417992 | doi = 10.1016/j.bbr.2020.113098 | s2cid = 230507941 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Pillinger T, McCutcheon RA, Vano L, Mizuno Y, Arumuham A, Hindley G, Beck K, Natesan S, Efthimiou O, Cipriani A, Howes OD | title = Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis | language = English | journal = The Lancet. Psychiatry | volume = 7 | issue = 1 | pages = 64–77 | date = January 2020 | pmid = 31860457 | pmc = 7029416 | doi = 10.1016/S2215-0366(19)30416-X }}</ref><ref>{{cite journal | vauthors = Wilson S, Anderson K, Baldwin D, Dijk DJ, Espie A, Espie C, Gringras P, Krystal A, Nutt D, Selsick H, Sharpley A | title = British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders: An update | journal = Journal of Psychopharmacology | volume = 33 | issue = 8 | pages = 923–947 | date = August 2019 | pmid = 31271339 | doi = 10.1177/0269881119855343 | s2cid = 195797603 | url = https://eprints.soton.ac.uk/433092/1/BAP_sleep_consensus_update_DSB_19032019.docx }}</ref> |
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Olanzapine has been recommended to be used in ] regimens in people receiving chemotherapy that has a high risk for vomiting.<ref>{{cite journal | vauthors = Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, Danso MA, Dennis K, Dupuis LL, Dusetzina SB, Eng C, Feyer PC, Jordan K, Noonan K, Sparacio D, Somerfield MR, Lyman GH | title = Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update | journal = Journal of Clinical Oncology | volume = 35 | issue = 28 | pages = 3240–3261 | date = October 2017 | pmid = 28759346 | pmc = 4876353 | doi = 10.1200/JCO.2017.74.4789 }}</ref> |
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Olanzapine has been studied as an ], particularly for the control of ] (CINV).<ref>{{cite journal | vauthors = Sutherland A, Naessens K, Plugge E, Ware L, Head K, Burton MJ, Wee B | title = Olanzapine for the prevention and treatment of cancer-related nausea and vomiting in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 9 | pages = CD012555 | date = September 2018 | pmid = 30246876 | pmc = 6513437 | doi = 10.1002/14651858.CD012555.pub2 }}</ref> |
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In general, olanzapine appears to be about as effective as ] for the prevention of CINV, though some concerns remain about its use in this population. For example, concomitant use of ] or haloperidol increases the risk for extrapyramidal symptoms. Otherwise, olanzapine appears to be fairly well tolerated for this indication, with somnolence being the most common side effect.<ref name="Schwartzberg">{{cite journal | vauthors = Schwartzberg L | title = Getting it right the first time: recent progress in optimizing antiemetic usage | journal = Supportive Care in Cancer | volume = 26 | issue = Suppl 1 | pages = 19–27 | date = March 2018 | pmid = 29556812 | pmc = 5876255 | doi = 10.1007/s00520-018-4116-2 }}</ref> Olanzapine is more effective than metoclopramide for breakthrough CINV.<ref>{{cite journal | vauthors = Navari RM, Nagy CK, Gray SE | title = The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy | journal = Supportive Care in Cancer | volume = 21 | issue = 6 | pages = 1655–1663 | date = June 2013 | pmid = 23314603 | doi = 10.1007/s00520-012-1710-6 }}</ref> It is also more effective than placebo when added to a combination of palonosetron, dexamethasone and aprepitant.<ref>{{cite journal | vauthors = Yanai T, Iwasa S, Hashimoto H, Ohyanagi F, Takiguchi T, Takeda K, Nakao M, Sakai H, Nakayama T, Minato K, Arai T, Suzuki K, Shimada Y, Nagashima K, Terakado H, Yamamoto N | title = A double-blind randomized phase II dose-finding study of olanzapine 10 mg or 5 mg for the prophylaxis of emesis induced by highly emetogenic cisplatin-based chemotherapy | journal = International Journal of Clinical Oncology | volume = 23 | issue = 2 | pages = 382–388 | date = April 2018 | pmid = 29039073 | doi = 10.1007/s10147-017-1200-4 }}</ref> |
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Olanzapine has been considered as part of an ] approach for schizophrenia. The Prevention through Risk Identification, Management, and Education <!-- (PRIME) --> study, funded by the ] and Eli Lilly, tested the hypothesis that olanzapine might prevent the onset of psychosis in people at very high risk for schizophrenia. The study examined 60 patients with ], who were at an estimated risk of 36–54% of developing schizophrenia within a year and treated half with olanzapine and half with placebo.<ref>{{cite journal | vauthors = McGlashan TH, Zipursky RB, Perkins D, Addington J, Miller TJ, Woods SW, Hawkins KA, Hoffman R, Lindborg S, Tohen M, Breier A | title = The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. I. Study rationale and design | journal = Schizophrenia Research | volume = 61 | issue = 1 | pages = 7–18 | date = May 2003 | pmid = 12648731 | doi = 10.1016/S0920-9964(02)00439-5 | s2cid = 1118339 }}</ref> In this study, patients receiving olanzapine did not have a significantly lower risk of progressing to psychosis (16.1% vs 37.9%). Olanzapine was effective for treating the prodromal symptoms but was associated with significant weight gain.<ref>{{cite journal | vauthors = McGlashan TH, Zipursky RB, Perkins D, Addington J, Miller T, Woods SW, Hawkins KA, Hoffman RE, Preda A, Epstein I, Addington D, Lindborg S, Trzaskoma Q, Tohen M, Breier A | title = Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis | journal = The American Journal of Psychiatry | volume = 163 | issue = 5 | pages = 790–799 | date = May 2006 | pmid = 16648318 | doi = 10.1176/appi.ajp.163.5.790 | url = https://cdr.lib.unc.edu/downloads/z603r0580 }}</ref> |
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== References == |
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{{Reflist}} |
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== External links == |
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{{Commons category}} |
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* {{cite news |url=https://www.nytimes.com/2007/01/05/business/05drug.html |title=Lilly Settles With 18,000 Over Zyprexa | vauthors = Alex B |work=] |date=5 January 2007 }} |
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