Reference Design <strong>CYP</strong>2D6 alleles Population Antipsychotics Outcome measure OutcomeKohlrausch 2008(54)Panagiotidis 2007(47)Plesnicar 2006(38)Riedel 2005(55)CohortRetrospectiveLongitudinal(12-24 weeks)CohortProspectiveCross sectionalCohortProspectiveCross sectionalCohortProspectiveLongitudinal(6 weeks)*2, …,*6, *9, *10, *15,*17,*35,*40,*41duplications*3, *4, *5duplication*2, …,*6, *8,* …,*12,*14,*15N=183Caucasian(7 PMs, 15 IMs, 152 EMs, 9UMs)N=26Ethnicity NR, assumedCaucasian (Sweden)Schizophrenia andschizo<strong>af</strong>fective disorder(DSM-IV)Outpatients(1 PM, 8 IMs, 16 EMs and 1UM)N=131CaucasiansSchizophrenia or schizo<strong>af</strong>fecti<strong>ved</strong>isorder (DSM-IV)Outpatients(6 PMs, 125 non PMs)*4, *6, *14 N=51Ethnicity not reported,assumed Caucasian(Germanychizophrenia (DSM-IV)(45 EMs, 6 IMs, 0 PMs)Any FGA(mostly haloperidoland chlorpromazine)Haloperidol decanoate(maintance monotherapy)Haloperidol,zuclopenthixol,fluphenazine orrisperidon(maintenancetherapy)Efficacy: Treatment-refractoryADRs: EPS (ESRS)Efficacy (PANNS)Kinetics: Peak and troughSS-conc.Efficacy: (PANNS)ADRs: EPS (Parkinsonism(SAS)), (TD (AIMS)),(akathisia (BAS))Risperidon Efficacy: Treatmentresponse, e.g. improve>30% (PANNS)Kinetics: Plasma conc., MRPM vs. EM: NS: OR = 0.73 [95% CI: 0.14,3.87][C]ADRs: EM vs. IM: EPS: NS (p=0.24)PANNS: EM vs. IM: NS: (p=0.63)Excluded from meta-analysis: Continuousdata.Efficacy: PM vs. EM/IM/UM: NSEPS: PM vs. EM/IM/UM: NS: OR =1.19[95% CI: 0.21, 6.78] [C]Efficacy: IMs vs. EMs: NSKinetics: IMs vs. EMs: NSExcluded from meta-analysis: Continuousdata.ADRs = Adverse drug reactions AIMS = abnormal involuntary movement scale BAS= Barnes akathisia scaleBPRS=Brief Psychiatric Rating Scale [C]=Calculated by reviewer (GJ) using Review Manager 51, CGI= Clinical Global Impression ScaleDIESS = Drug induced extrapyramidal symptom Score EM=Extensive metabolizer EPS= Extra pyramidale side effectsESRS= Extra pyramidale symptoms rating scale FGA=First Ggneration antipsycotics GAS = Global Assessment ScaleIM=Intermediate metabolizer NS=Non significant NR=Not reportedMR=Metabolic Ratio PANNS=Positive and negative syndrome scale PM = Poor metabolizerSADS= Schedule for <strong>af</strong>fective Disorders and Schizophrenia TD = Tardive dyskinesia TDRS=Tardive dyskinesia rating scale[S]=Stated in manuscript SAS=Simpson and Angus SS=steady stateUM= Ultra rapid metabolizer1 Review Manager (RevMan) [Computer program]. Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.110 <strong>Rutinebrug</strong> <strong>af</strong> <strong>CYP</strong>-<strong>test</strong> <strong>ved</strong> <strong>antipsykotisk</strong> <strong>behandling</strong>
Bilag 5 PM’ere versus EM’ere metaanalysetabelStudie PM PM EM EM Vægt Odds Ratio(bivirkninger) (total) (bivirkninger) (total)M-H, Fixed, 95% CIC Andreassen (Nor)(TD ) 1997 5 8 13 43 17.4% 3.85 [0.80, 18.53]C Armstrong 1997 4 5 18 43 8.5% 5.56 [0.57, 53.96]C Brochm (GER) (EPS) 2002 4 5 24 154 3.4% 21.67 [2.32, 202.34] EM’ere og IM’ere er poolet i kontrolgruppen.Dette betyder, at studdiet bidrager med etkonservativt etsimat. Selvom studiet fjernesfra analysen forbliver det samlede resultatethøjsignifikant.C Jaanson (Est)(EPS) 2002 4 4 20 35 5.7% 6.80 [0.34, 136.04]C Lohmann (GER) (TD) 2003 4 7 31 68 28.3% 1.59 [0.33, 7.66]C Plesnicar (Slo) (EPS) 2006 2 6 36 125 25.0% 1.24 [0.22, 7.05]C Scorda (Swe) (EPS) 2000 4 4 33 65 5.4% 8.73 [0.45, 168.72]C Topic (Cro) (EPS) 2000 5 6 12 38 6.2% 10.83 [1.14, 103.13]NoteTotal (95% CI) 45 571 100.0% 4.18 [2.14, 8.16]Total events 32 187Heterogeneity: Chi² = 6.51, df = 7 (P = 0.48); I² = 0%Test for overall effect: Z = 4.19 (P < 0.0001)C: Caucasian, A: asian, TD: tardive dyskinesia, PM: poor metabolizer, EM: extensive metabolizer, M-H: Mantel-Haenszel, CI: confidence interval, EPS: extrapyramidal side effects111 <strong>Rutinebrug</strong> <strong>af</strong> <strong>CYP</strong>-<strong>test</strong> <strong>ved</strong> <strong>antipsykotisk</strong> <strong>behandling</strong>
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Rutinebrug af CYP-test vedantipsyko
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IndholdHvad er Medicinsk Teknologiv
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Hvad er Medicinsk Teknologivurderin
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TeknologiCYP-testen er en gentest.
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Samlet påviser dette studie, at en
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sættelse. Dette skyldes den store
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SummaryIntroductionA large part of
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• Are CYP2D6 and/or CYP2C19 geno
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The costs of pharmacy-dispensed dru
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Sundhedsstyrelsen vil gerne takke p
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1 Introduktion1.1 BaggrundDen medik
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faktor for testens anvendelighed. S
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lægens ordination af såvel antips
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NomenklaturCYP-enzymerne inddeles i
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I det følgende præsenteres egne s
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Figur 2 Studiepopulationerne i stud
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ner. Således er de hyppigste mutat
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lerens kendskab til CYP2D6-genotype
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3.3 Diskussion af resultaterFra CYP
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I RCT'et er valgt at vurdere effekt
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CYP2C19. Ud fra et teoretisk ration
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Den begrænsede eksisterende viden
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4.2 ResultaterDet centrale spørgsm
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med en læge fra det afsnit, han er
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• Til tværfaglige behandlingsko
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liver det tydeligt, at CYP-testen k
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Lægerne i DPC udtrykker i spørges
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- Page 88 and 89: 8 Referencer1. Lieberman JA, Stroup
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- Page 96 and 97: 109. Psykiatrisk Center Sankt Hans.
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- Page 102 and 103: Statistiske analyserBehandlingspers
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- Page 106 and 107: Reference Design CYP2D6 alleles Pop
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- Page 118 and 119: Symptom Spørgsmål Rating af svær
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- Page 122 and 123: Bilag 8 Søgebeskrivelse: socioetis
- Page 124 and 125: Embase((Mental disease.mp. or menta
- Page 126 and 127: York CRD-databasernePharmacogenetic
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- Page 150 and 151: Samtlige genotyper:CYP2D6Genotype A
- Page 152 and 153: CYP 2D6 vejledninger:Tabel 1. Hurti
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- Page 157 and 158: (19-hydroxy-risperidon).Det må for
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Tabel 5. CYP 2C19-tilpasset doserin