Estats mixtes, viratges i antidepressius: estudi d'una cohort de pacients bipolars

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(1)Estats mixtes, viratges i antidepressius: estudi d´una cohort de pacients bipolars Marc Valentí Ribas.  . ADVERTIMENT. La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX (www.tdx.cat) i a través del Dipòsit Digital de la UB (diposit.ub.edu) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en activitats d’investigació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposició des d’un lloc aliè al servei TDX ni al Dipòsit Digital de la UB. No s’autoritza la presentació del seu contingut en una finestra o marc aliè a TDX o al Dipòsit Digital de la UB (framing). Aquesta reserva de drets afecta tant al resum de presentació de la tesi com als seus continguts. En la utilització o cita de parts de  la tesi és obligat indicar el nom de la persona autora. ADVERTENCIA. La consulta de esta tesis queda condicionada a la aceptación de las siguientes condiciones de uso: La difusión de esta tesis por medio del servicio TDR (www.tdx.cat) y a través del Repositorio Digital de la UB (diposit.ub.edu) ha sido autorizada por los titulares de los derechos de propiedad intelectual únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con finalidades de lucro ni su difusión y puesta a disposición desde un sitio ajeno al servicio TDR o al Repositorio Digital de la UB. No se autoriza la presentación de su contenido en una ventana o marco ajeno a TDR o al Repositorio Digital de la UB (framing). Esta reserva de derechos afecta tanto al resumen de presentación de la tesis como a sus contenidos. En la utilización o cita de partes de la tesis es obligado indicar el nombre de la persona autora.. WARNING. On having consulted this thesis you’re accepting the following use conditions: Spreading this thesis by the TDX (www.tdx.cat) service and by the UB Digital Repository (diposit.ub.edu) has been authorized by the titular of the intellectual property rights only for private uses placed in investigation and teaching activities. Reproduction with lucrative aims is not authorized nor its spreading and availability from a site foreign to the TDX service or to the UB Digital Repository. Introducing its content in a window or frame foreign to the TDX service or to the UB Digital Repository is not authorized (framing). Those rights affect to the presentation summary of the thesis as well as to its contents. In the using or citation of parts of the thesis it’s obliged to indicate the name of the author..

(2)    .  .     . ESTATS MIXTES, VIRATGES I ANTIDEPRESSIUS: ESTUDI D´UNA COHORT DE PACIENTS BIPOLARS    Tesi presentada per: 0DUF9DOHQWt5LEDV  3HUDREWHQLUHOWtWROGH'RFWRUSHUOD8QLYHUVLWDWGH%DUFHORQD    Supervisat per:  3URIHVVRU(GXDUG9LHWD3DVFXDO. Programa Doctorat Medicina Departament de Psiquiatria i Psicobiologia Clínica Facultat de Medicina Universitat de Barcelona. )HEUHU.

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(6) Als meus pares, Josep i Carme..

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(10) TAULA DE CONTINGUTS. 1. Justificació. 1. 2. Introducció. 7. a. Aproximació general al trastorn bipolar. 9. b. La depressió bipolar i el seu tractament. 14. c. Desenvolupament d’una fase mixta. 16. d. Viratge de depressió a hipo(mania) secundari al tractament amb antidepressius. 25. e. Acceleració de cicles. 31. f. Manteniment del tractament antidepressiu després de la remissió simptomàtica. 33. 3. Objectius i hipòtesis. 35. a. Objectius. 37. b. Hipòtesis. 39. 4. Mètodes. 41. 5. Resultats. 47. 6. Publicacions. 55. 7. Discussió. 73. 8. Estudis futurs. 91. 9. Limitacions. 95. 10. Conclusions. 99. 11. Referències bibliogràfiques. 103.

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(12) 1. JUSTIFICACIÓ. . 1.

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(45) O ~VFRQWLQXDWGHODPHGLFDFLyDQWLGHSUHVVLYDLTXHVREUHWRWHUDVXEVWDQFLDOPHQWPHQRU TXHHOULVFGHUHFDLJXGDGHSUHVVLYD 3HUUHFRO]DUO¶HVWXGLHOPDWHL[JUXSG¶$OWVKXOHUHWDO  SRUWDUHQDWHUPHXQDOWUH HVWXGLUHWURVSHFWLXDPESDFLHQWVELSRODUV DPE7%3,LDPE7%3,, WUDFWDWV DPEXQDQWLGHSUHVVLXDIHJLWDXQHVWDELOLW]DGRUGHO¶HVWDWG¶jQLPSHUXQHSLVRGL GHSUHVVLXDJXW(OVUHVXOWDWVG¶DTXHVWLQGLFDUHQTXHODVXVSHQVLy FRPSDUDWDPEOD FRQWLQXDFLy GHOWUDFWDPHQWDQWLGHSUHVVLXGLQVGHOSULPHUDQ\SRVWHULRUDODUHPLVVLy DXJPHQWDGHPDQHUDVLJQLILFDWLYDHOULVFGHUHFDLJXGDGHSUHVVLYD                . 34. .

(46) 3. OBJECTIUS I HIPÒTESIS. 35. .

(47) . 36.

(48)  D(OVobjectius G¶DTXHVWWUHEDOOVyQHOVVHJHQWV   'HWHUPLQDUHOVIDFWRUVFOtQLFVDVVRFLDWVDOGHVHQYROXSDPHQWG¶XQHSLVRGLGH FDUDFWHUtVWLTXHVPL[WHVHQSDFLHQWVGLDJQRVWLFDWVGHWUDVWRUQELSRODUWLSXV,TXHKDJLQ UHEXWWUDFWDPHQWDPEDQWLGHSUHVVLXV  'HWHUPLQDUHOSDSHUGHOVDQWLGHSUHVVLXVHQHOFXUVLSURQzVWLFGHOWUDVWRUQELSRODULOD VHYDUHODFLyDPEHOGHVHQYROXSDPHQWG¶HSLVRGLVGHFDUDFWHUtVWLTXHVPL[WHV  'HWHUPLQDUHOVIDFWRUVFOtQLFVUHODFLRQDWVDPEO¶DSDULFLyG¶XQYLUDWJHGHGHSUHVVLyD KLSRPDQLDPDQLDRHSLVRGLPL[WHGXUDQWOHVYXLWVHWPDQHVGHVSUpVGHODLQWURGXFFLy G XQDQWLGHSUHVVLXRGHVSUpVG¶KDYHUQHDXJPHQWDWODGRVL          . 37. .

(49) . 38.

(50)   E/HVhipòtesis G¶DTXHVWHVWXGLVyQ   /¶DSDULFLyGHIDVHVPL[WHVLGHYLUDWJHVV¶DVVRFLDUjDPEXQPDMRU~VG¶DQWLGHSUHVVLXV DOOODUJGHODPDODOWLD  /¶DSDULFLyGHIDVHVPL[WHVLGHYLUDWJHVHVWDUjUHODFLRQDWDPEXQDPDMRUJUDYHWDW ORQJLWXGLQDOGHODPDODOWLD  (OVSDFLHQWVGLDJQRVWLFDWVGHWUDVWRUQELSRODUTXHGHVHQYROXSLQIDVHVPL[WHV SUHVHQWDUDQXQDPDMRUVXwFLGDELOLWDWWDQWSHOTXHIDDODLGHDFLyFRPSHUDOHV WHPSWDWLYHV  (OVSDFLHQWVELSRODUVWLQGUDQXQDPDMRUSUREDELOLWDWG¶DSDULFLyGHIDVHVPL[WHVLGH GHVHQYROXSDPHQWGHYLUDWJHVDPEO ~VG¶DQWLGHSUHVVLXV7ULFtFOLFVTXHQRSDVDPEO¶~V G¶DQWLGHSUHVVLXV,QKLELGRUV6HOHFWLXVGHOD5HFDSWDFLyGH6HURWRQLQDRG ,QKLELGRUVGHOD 5HFDSWDFLyGH6HURWRQLQDL1RUDGUHQDOLQD      . 39. .

(51) . 40.

(52) 4. MÈTODES. 41. .

(53) . 42.

(54) $TXHVWDWHVLHVWjIRUPDGDSHUGRVDUWLFOHVTXHV¶KDQGHVHQYROXSDWDOOODUJGHODPHYD IRUPDFLyHQLQYHVWLJDFLyGHODEHFD³5tR+RUWHJD´$PEGyVWUHEDOOVGHOVTXDOVDSDUHF FRPDSULPHUDXWRUKDQHVWDWSXEOLFDWVHQUHYLVWHVLQGH[DGHVLDPEIDFWRUG¶LPSDFWHHQ HOSULPHUGHFLOGHO¶HVSHFLDOLWDW /DGHVFULSFLyGHWDOODGDGHOHVFDUDFWHUtVWLTXHVGHODPRVWUDHOVSURFHGLPHQWVLHOV PqWRGHVHVWDGtVWLFVXWLOLW]DWVHVWUREHQHQFDGDXQGHOVDUWLFOHVFRUUHVSRQHQWV (OVWUHEDOOVUHDOLW]DWVHVFRUUHVSRQHQDPEOHVKLSzWHVLVGHO¶HVWXGLVHJRQVHVGHWDOODD FRQWLQXDFLy  Hipòtesi 1: “L’aparició de fases mixtes i de viratges s’associarà amb un major ús d’antidepressius al llarg de la malaltia” Estudi: Valentí M3DFFKLDURWWL,5RVD$5%RQQtQ&03RSRYLF'1LYROL$0 0XUUX$*UDQGH,&RORP)9LHWD(%LSRODU0L[HG(SLVRGHVDQG$QWLGHSUHVVDQWV$ &RKRUW6WXG\RI%LSRODU,'LVRUGHU3DWLHQWV%LSRODU'LVRUG   Estudi: Valentí M3DFFKLDURWWL,%RQQtQ&05RVD$53RSRYLF'1LYROL$0 *RLNROHD-00XUUX$8QGXUUDJD-&RORP)9LHWD(5LVN)DFWRUVIRU $QWLGHSUHVVDQW5HODWHG6ZLWFKWR0DQLD-&OLQ3V\FKLDWU\      . 43. .

(55) Hipòtesi 2: “L’aparició de fases mixtes i de viratges estarà relacionat amb una major gravetat longitudinal de la malaltia” Estudi: Valentí M3DFFKLDURWWL,5RVD$5%RQQtQ&03RSRYLF'1LYROL$0 0XUUX$*UDQGH,&RORP)9LHWD(%LSRODU0L[HG(SLVRGHVDQG$QWLGHSUHVVDQWV$ &RKRUW6WXG\RI%LSRODU,'LVRUGHU3DWLHQWV%LSRODU'LVRUG   Estudi: Valentí M3DFFKLDURWWL,%RQQtQ&05RVD$53RSRYLF'1LYROL$0 *RLNROHD-00XUUX$8QGXUUDJD-&RORP)9LHWD(5LVN)DFWRUVIRU $QWLGHSUHVVDQW5HODWHG6ZLWFKWR0DQLD-&OLQ3V\FKLDWU\. Hipòtesi 3: “Els pacients diagnosticats de trastorn bipolar que desenvolupin fases mixtes presentaran una major suïcidabilitat, tant pel que fa a la ideació com per a les temptatives” Estudi: Valentí M3DFFKLDURWWL,5RVD$5%RQQtQ&03RSRYLF'1LYROL$0 0XUUX$*UDQGH,&RORP)9LHWD(%LSRODU0L[HG(SLVRGHVDQG$QWLGHSUHVVDQWV$ &RKRUW6WXG\RI%LSRODU,'LVRUGHU3DWLHQWV%LSRODU'LVRUG       . 44. .

(56)    Hipòtesi 4: “Els pacients bipolars tindran una major probabilitat d’aparició de fases mixtes i de desenvolupament de viratges amb l'ús d’antidepressius Tricíclics que no pas amb l’ús d’antidepressius Inhibidors Selectius de la Recaptació de Serotonina o d'Inhibidors de la Recaptació de Serotonina i Noradrenalina” Estudi: Valentí M3DFFKLDURWWL,5RVD$5%RQQtQ&03RSRYLF'1LYROL$0 0XUUX$*UDQGH,&RORP)9LHWD(%LSRODU0L[HG(SLVRGHVDQG$QWLGHSUHVVDQWV$ &RKRUW6WXG\RI%LSRODU,'LVRUGHU3DWLHQWV%LSRODU'LVRUG   Estudi: Valentí M3DFFKLDURWWL,%RQQtQ&05RVD$53RSRYLF'1LYROL$0 *RLNROHD-00XUUX$8QGXUUDJD-&RORP)9LHWD(5LVN)DFWRUVIRU $QWLGHSUHVVDQW5HODWHG6ZLWFKWR0DQLD-&OLQ3V\FKLDWU\           . 45. .

(57) . 46.

(58)      . 5. RESULTATS. 47. .

(59) . 48.

(60)    Valentí M3DFFKLDURWWL,5RVD$5%RQQtQ&03RSRYLF'1LYROL$00XUUX$ *UDQGH,&RORP)9LHWD(%LSRODU0L[HG(SLVRGHVDQG$QWLGHSUHVVDQWV$&RKRUW 6WXG\RI%LSRODU,'LVRUGHU3DWLHQWV%LSRODU'LVRUG    Valentí M3DFFKLDURWWL,%RQQtQ&05RVD$53RSRYLF'1LYROL$0*RLNROHD -00XUUX$8QGXUUDJD-&RORP)9LHWD(5LVN)DFWRUVIRU$QWLGHSUHVVDQW5HODWHG 6ZLWFKWR0DQLD-&OLQ3V\FKLDWU\  (OVGRVDUWLFOHVSXEOLFDWVTXHHVSUHVHQWHQHQDTXHVWWUHEDOOG¶LQYHVWLJDFLyVXPHQXQ IDFWRUG¶LPSDFWH ,) GH  .   . 49. .

(61) . 50.

(62) Resum dels resultats. Valentí M, Pacchiarotti I, Rosa AR, Bonnín CM, Popovic D, Nivoli AM, Murru A, Grande I, Colom F, Vieta E. Bipolar Mixed Episodes and Antidepressants: A Cohort Study of Bipolar I Disorder Patients. Bipolar Disord 2011;13(2):145-154.. /¶REMHFWLXG¶DTXHVWHVWXGLIRXGHWHUPLQDUHOVIDFWRUVDVVRFLDWVDPEHOGHVHQYROXSDPHQW G¶HSLVRGLVPL[WHVFDUDFWHULW]DWVSHUODSUHVqQFLDFRQFRPLWDQWGHVtPSWRPHVG¶DPEGyV SROVDIHFWLXVGXUDQWO¶HYROXFLyGHODPDODOWLDHQSDFLHQWVGLDJQRVWLFDWVGHWUDVWRUQ ELSRODUWLSXV,LWUDFWDWVDPEDQWLGHSUHVVLXVDL[tFRPHVEULQDUHOUROGHOVDQWLGHSUHVVLXV HQHOFXUVLHOSURQzVWLFGHOWUDVWRUQ 9DPLQFORXUHXQDPRVWUDGHSDFLHQWVVHJXLWVGXUDQWXQSHUtRGHGHILQVDDQ\VHQ HO3URJUDPDGH7UDVWRUQV%LSRODUVGHO +RVSLWDO&OtQLFGH%DUFHORQDLYDPFRPSDUDU DTXHOOVTXHGHVHQYROXSDUHQFRPDPtQLPXQHSLVRGLPL[WHGXUDQWHOVHJXLPHQW Q   DPEDTXHOOVTXHPDLWLQJXHUHQXQHSLVRGLPL[WH Q  UHVSHFWHDOHVYDULDEOHV FOtQLTXHV (OVUHVXOWDWVGHWHUPLQDUHQTXHDOYROWDQWGHOGHOVSDFLHQWVDPEWUDVWRUQELSRODU WLSXV,WUDFWDWVDPEDQWLGHSUHVVLXVGHVHQYROXSDUHQFRPDPtQLPXQHSLVRGLPL[WHGXUDQW HOFXUVGHODVHYDPDODOWLD 1RHVGHWHFWDUHQGLIHUqQFLHVGHJqQHUHHQWUHHOVGRVJUXSV (VWUREDUHQYDULHVGLIHUqQFLHVFOtQLTXHVHQWUHHOVGRVJUXSVSHUzGHVSUpVG¶DSOLFDUXQD DQjOLVLGHUHJUHVVLyORJtVWLFDQRPpVHOQRPEUHGHWHPSWDWLYHVVXwFLGHV S O¶~V G DQWLGHSUHVVLXV,QKLELGRUVGHOD5HFDSWDFLyGH6HURWRQLQDL1RUDGUHQDOLQD S  OD WD[DGHYLUDWJHV S  LHOQRPEUHG¶DQ\VG¶HYROXFLyGHODPDODOWLD S  . 51. .

(63) HVWDYHQVLJQLILFDWLYDPHQWDVVRFLDWVDPEHOGHVHQYROXSDPHQWGHFRPDPtQLPXQ HSLVRGLPL[WHGXUDQWHOVHJXLPHQW &RPDFRQFOXVLyDTXHVWHVWXGLGHWHUPLQjTXHHOGHVHQYROXSDPHQWG¶HSLVRGLVPL[WHV HVWjDVVRFLDWDPEXQDWHQGqQFLDDODFURQLFLWDWDPEXQSLWMRUSURQzVWLFDPEXQQRPEUH PpVHOHYDWG¶HSLVRGLVGHSUHVVLXVLDPEXQPDMRU~VG¶DQWLGHSUHVVLXVHVSHFLDOPHQW ,QKLELGRUVGHOD5HFDSWDFLyGH6HURWRQLQDL1RUDGUHQDOLQD                   . 52. .

(64) Valentí M, Pacchiarotti I, Bonnín CM, Rosa AR, Popovic D, Nivoli AM, Goikolea JM, Murru A, Undurraga J, Colom F, Vieta E. Risk Factors for AntidepressantRelated Switch to Mania. J Clin Psychiatry.  (OWUDFWDPHQWGHODGHSUHVVLyELSRODUDPEDQWLGHSUHVVLXVpVXQWHPDTXHKDVXVFLWDWXQ DPSOLGHEDWDUUDQGHOHVGDGHVPHWRGROzJLFDPHQWSREUHVLLQVXILFLHQWVUHFRO]DQWHOVHX ~VLODFUHHQoDjPSOLDPHQWHVWHVDTXHHOVDQWLGHSUHVVLXVSRGHQLQGXLUQRXVHSLVRGLV G DQRUPDOHOHYDFLyDQtPLFDRTXHSRGHQDFFHOHUDUODWD[DGHFLFODFLy (OSUHVHQWHVWXGLSUHWpQLGHQWLILFDUHOVIDFWRUVGHULVFFOtQLFVDVVRFLDWVDYLUDWJHGH GHSUHVVLyD KLSR PDQLDRHVWDWPL[WHGLQVGHOHVVHWPDQHVSRVWHULRUVDODLQWURGXFFLy G¶XQDQWLGHSUHVVLXRGHVSUpVG DXJPHQWDUQHODGRVLHQXQGLVVHQ\SURVSHFWLXL ORQJLWXGLQDO 9DPLQFORXUHSDFLHQWVDPEWUDVWRUQELSRODUWLSXV,L,,FRQVHFXWLYDPHQWGHSULPLWVL IRUHQWUDFWDWVDPEDQWLGHSUHVVLXVHOVTXDOVV¶DIHJLUHQDODSDXWDIDUPDFROzJLFDSUHVFULWD SUqYLDPHQW HVWDELOLW]DGRUVGHO¶HVWDWG¶jQLPLRDQWLSVLFzWLFVDWtSLFV &DSSDFLHQW SUHQJXpPRQRWHUjSLDDQWLGHSUHVVLYD(QSDFLHQWV  HVGHWHFWjXQYLUDWJH UHODFLRQDWDPEHOWUDFWDPHQWPHQWUHTXHHQSDFLHQWV  QRHVGHWHFWj $PEGyVJUXSVIRUHQFRPSDUDWVDPESURFHGLPHQWV$129$L&KLTXDGUDW /HVSULQFLSDOVGLIHUqQFLHVFOtQLTXHVVLJQLILFDWLYDPHQWDVVRFLDGHVDPEHO GHVHQYROXSDPHQWG¶XQYLUDWJHGHO¶HVWDWG¶jQLPUHODFLRQDWDPEHOWUDFWDPHQWGHVSUpVGH UHDOLW]DUXQDDQjOLVLGHUHJUHVVLyORJtVWLFDIRUHQXQDPDMRUWD[DGHYLUDWJHVSUHYLVXQD PHQRUWD[DGHUHVSRVWDDDQWLGHSUHVVLXVLXQDHGDWGHGHEXWGHODPDODOWLDPpVSUHFRo &RPDFRQFOXVLyDTXHVWHVWXGLGHWHUPLQjTXHHOVSDFLHQWVELSRODUVTXHSUHVHQWDYHQXQ PDMRUULVFGHYLUDWJHHUHQDTXHOOVDPEXQGHEXWGHODPDODOWLDPpVSUHFRoLXQFXUVGHO WUDVWRUQFDUDFWHULW]DWSHUXQDPHQRUWD[DGHUHVSRVWDDDQWLGHSUHVVLXVLXQDPDMRUWD[DGH. 53. .

(65) YLUDWJHV&DOUHPDUFDUTXHHOQRVWUHHVWXGLWUREjTXHXQPDMRUQRPEUHG¶H[SRVLFLRQV SUqYLHVDDQWLGHSUHVVLXVQRHVWjDVVRFLDWDPEHOGHVHQYROXSDPHQWGHYLUDWJHVUHODFLRQDWV DPEDQWLGHSUHVVLXV                                       . 54. .

(66) 6. PUBLICACIONS. 55. .

(67) . 56.

(68) ª 2011 John Wiley and Sons A/S. Bipolar Disorders 2011: 13: 145–154. BIPOLAR DISORDERS. Original Article. Bipolar mixed episodes and antidepressants: a cohort study of bipolar I disorder patients Valentı́ M, Pacchiarotti I, Rosa AR, Bonnı́n CM, Popovic D, Nivoli AMA, Murru A, Grande Í, Colom F, Vieta E. Bipolar mixed episodes and antidepressants: a cohort study of bipolar I disorder patients. Bipolar Disord 2011: 13: 145–154. ª 2011 The Authors. Journal compilation ª 2011 John Wiley & Sons A ⁄ S.. Marc Valentı́, Isabella Pacchiarotti, Adriane R Rosa, C Mar Bonnı́n, Dina Popovic, Alessandra M A Nivoli, Andrea Murru, Íria Grande, Francesc Colom and Eduard Vieta. Objectives: The aim of this study was to elucidate the factors associated with the occurrence of mixed episodes, characterized by the presence of concomitant symptoms of both affective poles, during the course of illness in bipolar I disorder patients treated with an antidepressant, as well as the role of antidepressants in the course and outcome of the disorder.. Bipolar Disorders Program, Clinical Institute of Neuroscience, Hospital Clı́nic Barcelona, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain. Method: We enrolled a sample of 144 patients followed for up to 20 years in the referral Barcelona Bipolar Disorder Program and compared subjects who had experienced at least one mixed episode during the follow-up (n = 60) with subjects who had never experienced a mixed episode (n = 84) regarding clinical variables. Results: Nearly 40% of bipolar I disorder patients treated with antidepressants experienced at least one mixed episode during the course of their illness; no gender differences were found between two groups. Several differences regarding clinical variables were found between the two groups, but after performing logistic regression analysis, only suicide attempts (p < 0.001), the use of serotonin norepinephrine reuptake inhibitors (p = 0.041), switch rates (p = 0.010), and years spent ill (p = 0.022) were significantly associated with the occurrence of at least one mixed episode during follow-up. Conclusions: The occurrence of mixed episodes is associated with a tendency to chronicity, with a poorer outcome, a higher number of depressive episodes, and greater use of antidepressants, especially serotonin norepinephrine reuptake inhibitors.. More than 40% of patients with bipolar disorder present with at least one mixed affective episode during the course of their illness (1, 2). Mixed state, an episode that is increasingly recognized as a nosological entity, is characterised by the presence of concomitant symptoms of both affective poles. doi: 10.1111/j.1399-5618.2011.00908.x Key words: antidepressants – bipolar disorder – depression – mania – mixed episode Received 2 August 2010, revised and accepted for publication 18 January 2011 Corresponding author: Eduard Vieta, M.D., Ph.D. Bipolar Disorders Program Clinical Institute of Neuroscience Hospital Clı́nic Barcelona Villarroel 170 08036, Barcelona, Spain Fax: +34-93-2275795 E-mail: evieta@clinic.ub.es. (3), and due to its clinical features, diagnostic difficulty, and treatment complexity represents one of the main challenges in the management of patients with bipolar disorder. Regarding the prevalence of mixed episodes, Vieta and Morralla (4) identified in 76 centers, the. EV has received research grants and has served as a consultant, advisor, or speaker for Almirall, AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., Forest, Geodon Richter, GlaxoSmithKline, Janssen-Cilag, Jazz, Lundbeck, Merck, Novartis, Organon, Otsuka, Pfizer, Sanofi-Aventis, Servier, Solvay, Schering-Plough, Takeda, United Biosource Corp., and Wyeth; and has received research funding from the Spanish Ministry of Innovation, the Spanish Ministry of Science and Education, the Stanley Medical Research Institute, and the 7th Framework Program of the European Union. FC has served as an advisory or speaker for AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., GlaxoSmithKline, Otsuka, Pfizer, Sanofi-Aventis, Tecnifar, and Shire. MV, IP, ARR, CMB, DP, AMAN, AM, and ÍG have no conflicts of interest to report.. 145.

Figure

Fig. 1. Diagram of subject flow.
Fig. 1. Diagram of subject flow. p.70
Table 1. Demographic, global social functioning, and clinical qualitative features differentiating patients with bipolar I disorder treated with antidepressants(ADs) without or with a history of mixed episode

Table 1.

Demographic, global social functioning, and clinical qualitative features differentiating patients with bipolar I disorder treated with antidepressants(ADs) without or with a history of mixed episode p.72
Table 3. Distribution of antidepressant (AD) class by each patient group

Table 3.

Distribution of antidepressant (AD) class by each patient group p.73
Table 2. Clinical and sociodemographic measures differentiating bipolar I disorder patients treated with antidepressants (ADs) without or with history of mixedepisode

Table 2.

Clinical and sociodemographic measures differentiating bipolar I disorder patients treated with antidepressants (ADs) without or with history of mixedepisode p.73
Table 4. Results from logistic regression analysis showing that only suicideattempts, the use of serotonin norepinephrine reuptake inhibitors (SNRIs),switch rates, and time spent ill (years) were significantly associated with theoccurrence of at least one mixed episode during follow-upa

Table 4.

Results from logistic regression analysis showing that only suicideattempts, the use of serotonin norepinephrine reuptake inhibitors (SNRIs),switch rates, and time spent ill (years) were significantly associated with theoccurrence of at least one mixed episode during follow-upa p.74
Table 1. Demographic, Global Social Functioning, and Clinical Qualitative Features Differentiating Patients With Antidepressant-Associated Switch at the Index Episode and Patients With No Antidepressant-Associated Switch at the Index Episode

Table 1.

Demographic, Global Social Functioning, and Clinical Qualitative Features Differentiating Patients With Antidepressant-Associated Switch at the Index Episode and Patients With No Antidepressant-Associated Switch at the Index Episode p.80
Table 3. Results From Logistic Regression Analysis Showed That Only Rate of Previous Antidepressant-Associated Switches, Rate of Previous Responses to Antidepressants, and Age at Onset Were Significantly Associated With the Occurrence of an Antidepressant-Related Switch

Table 3.

Results From Logistic Regression Analysis Showed That Only Rate of Previous Antidepressant-Associated Switches, Rate of Previous Responses to Antidepressants, and Age at Onset Were Significantly Associated With the Occurrence of an Antidepressant-Related Switch p.81
Table 2. Demographic and Clinical Quantitative Features Differentiating Patients With Antidepressant-Associated Switch at the Index Episode and Patients With No

Table 2.

Demographic and Clinical Quantitative Features Differentiating Patients With Antidepressant-Associated Switch at the Index Episode and Patients With No p.81
FIGURA 1��

FIGURA 1��

p.87
FIGURA 2

FIGURA 2

p.91
FIGURA 3

FIGURA 3

p.92
FIGURA 4

FIGURA 4

p.95
FIGURA 5

FIGURA 5

p.99
FIGURA 6

FIGURA 6

p.100

Referencias

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