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).

Elizabeth Jj Berm,Arne J Risselada,Rob M Kok,Bob Wilffert,Jacobus Rbj Brouwers,Ton Dhondt,Maarten Postma,Marjolein Boshuisen,Rob Van Marum,Laura Breuning,Richard C Oude Voshaar,Harry Venema,Liesbeth Vleugel,Jan G Maring,Hans Mulder,Eelko Hak,Paul Af Jansen

doi:10.1186/s13063-015-0561-0

Abstract

BackgroundNortriptyline 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/DesignIn 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.DiscussionResults of this trial will guide policy-making with regard to pharmacogenetic screening prior to treatment with nortriptyline or venlafaxine among older patients with depression.Trial registrationClinicalTrials.gov: NCT01778907; registration date: 22 January 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0561-0) contains supplementary material, which is available to authorized users.

Highlights

Nortriptyline and venlafaxine are commonly used antidepressants for treatment of depression in older patients
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
major depressive disorder (MDD) can be treated with antidepressants, which are classified into different groups: selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressant (TCAs) and others (for example,. selective serotonin-noradrenaline reuptake inhibitors (SNRIs), mirtazapine, monoamine oxidase inhibitors)

Summary

Discussion

To the best of our knowledge, this is the first pragmatic randomized controlled trial designed to test whether CYP2D6 polymorphism genotyping among older depressed patients starting with nortriptyline or venlafaxine in clinical practice adds value to regular care. Results of this trial will generate evidence as to whether routinelybased genotype testing can reduce the time needed for dose-finding at the start of treatment and as a result reduce adverse drug reactions. All authors read and approved the final version of the manuscript

Background

Findings