title: Effects and cost-effectiveness of pharmacogenetic screening for CYP2D6 among older adults starting therapy with nortriptyline or venlafaxine: study protocol for a pragmatic randomized controlled trial (CYSCEtrial).
abstract: BACKGROUND
  Nortriptyline and venlafaxine are commonly used antidepressants for treatment of depression in older patients. Both drugs are metabolized by the polymorphic cytochrome P450-2D6 (CYP2D6) enzyme and guidelines for dose adaptations based on the CYP2D6 genotype have been developed. The CYP2D6 Screening Among Elderly (CYSCE) trial is designed to address the potential health and economic value of genotyping for CYP2D6 in optimizing dose-finding of nortriptyline and venlafaxine.
  
  
  METHODS
  In a pragmatic randomized controlled trial, patients diagnosed with a major depressive disorder according to the DSM-IV and aged 60 years or older will be recruited from psychiatric centers across the Netherlands. After CYP2D6 genotyping determined in peripheral blood obtained by finger-prick, patients will be grouped into poor, intermediate, extensive, or ultrarapid metabolizers. Patients with deviant genotype (that is poor, intermediate or ultrarapid genotype) will be randomly allocated to an intervention group in which the genotype and dosing advice is communicated to the treating physician, or to a control group in which patients receive care as usual. Additionally, an external reference group of patients with the extensive metabolizer genotype is included. Primary outcome in all groups is time needed to obtain an adequate blood level of the antidepressant drug. Secondary outcomes include adverse drug reactions measured by a shortened Antidepressant Side-Effects Checklist (ASEC), and cost-effectiveness of the screening.
  
  
  CONCLUSIONS
  Results of this trial will guide policy-making with regard to pharmacogenetic screening prior to treatment with nortriptyline or venlafaxine among older patients with depression.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01778907 ; registration date: 22 January 2013.
authors: Groningen Institute of Pharmacy, University of Groningen, Unit of Pharmacotherapy & Pharmaceutical Care, Antonius Deusinglaan 1, 9713AV, Groningen, The Netherlands. e.j.j.berm@rug.nl.
authors: Elizabeth J J
authors: EJ
authors: Berm
authors: Groningen Institute of Pharmacy, University of Groningen, Unit of Pharmacoepidemiology & Pharmacoeconomics, Groningen, The Netherlands. e.hak@rug.nl.|Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands. e.hak@rug.nl.
authors: Eelko
authors: E
authors: Hak
authors: Groningen Institute of Pharmacy, University of Groningen, Unit of Pharmacoepidemiology & Pharmacoeconomics, Groningen, The Netherlands. m.j.postma@rug.nl.|Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands. m.j.postma@rug.nl.
authors: Maarten
authors: M
authors: Postma
authors: Lentis, Dignis, Groningen, The Netherlands. m.boshuisen@lentis.nl.
authors: Marjolein
authors: M
authors: Boshuisen
authors: Departement of Old Age and Clinical Psychiatry, Reinier van Arkel Group, 's-Hertogenbosch, The Netherlands. l.breuning@rvagroep.nl.
authors: Laura
authors: L
authors: Breuning
authors: Groningen Institute of Pharmacy, University of Groningen, Unit of Pharmacotherapy & Pharmaceutical Care, Antonius Deusinglaan 1, 9713AV, Groningen, The Netherlands. jrbjbrouwers@stbebo.nl.|Department of Geriatric Medicine and Expertise Centere Pharmacotherapy in Old Persons, UMC Utrecht, Utrecht, The Netherlands. jrbjbrouwers@stbebo.nl.
authors: Jacobus R B J
authors: JR
authors: Brouwers
authors: Department of Old-age Psychiatry, GGZ-Noord Holland Noord, Heerhugowaard, The Netherlands. a.dhondt@ggz-nhn.nl.
authors: Ton
authors: T
authors: Dhondt
authors: Department of Geriatric Medicine and Expertise Centere Pharmacotherapy in Old Persons, UMC Utrecht, Utrecht, The Netherlands. p.a.f.jansen@umcutrecht.nl.
authors: Paul A F
authors: PA
authors: Jansen
authors: Department of Old Age, Parnassia Psychiatric Institute, The Hague, The Netherlands. r.kok@parnassia.nl.
authors: Rob M
authors: RM
authors: Kok
authors: Laboratory for Drug Analysis & Toxicology, Diaconessen Hospital Meppel & Bethesda Hospital Hoogeveen, Meppel, The Netherlands. maring@noorderboog.nl.
authors: Jan G
authors: JG
authors: Maring
authors: Department of Geriatric Medicine, Jeroen Bosch Hospital, 's Hertogenbosch, The Netherlands. r.v.marum@jbz.nl.|Department of General Practice & Elderly Care Medicine, VU University, Amsterdam, The Netherlands. r.v.marum@jbz.nl.
authors: Rob
authors: R
authors: van Marum
authors: Clinical Pharmacy, Wilhelmina Hospital Assen, Assen, The Netherlands. hans.mulder@wza.nl.
authors: Hans
authors: H
authors: Mulder
authors: University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Groningen, The Netherlands. r.c.oude.voshaar@umcg.nl.
authors: Richard C Oude
authors: RC
authors: Voshaar
authors: Clinical Pharmacy, Wilhelmina Hospital Assen, Assen, The Netherlands. arne.risselada@wza.nl.
authors: Arne J
authors: AJ
authors: Risselada
authors: Department of Old Age Psychiatry, GGZ Friesland, Leeuwarden, The Netherlands. harry.venema@ggzfriesland.nl.
authors: Harry
authors: H
authors: Venema
authors: Department of Old Age Psychiatry, GGZ inGeest, Haarlem, The Netherlands. l.vleugel@ggzingeest.nl.
authors: Liesbeth
authors: L
authors: Vleugel
authors: Groningen Institute of Pharmacy, University of Groningen, Unit of Pharmacotherapy & Pharmaceutical Care, Antonius Deusinglaan 1, 9713AV, Groningen, The Netherlands. b.wilffert@rug.nl.|Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands. b.wilffert@rug.nl.
authors: Bob
authors: B
authors: Wilffert
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005838:Genotype; D006801:Humans; D009661:Nortriptyline / Q000627:therapeutic use*; D010597:Pharmacogenetics; D018401:Sample Size; D000069470:Venlafaxine Hydrochloride / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D000069470:Venlafaxine Hydrochloride; D009661:Nortriptyline; D019389:Cytochrome P-450 CYP2D6
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