NCT01778907

Cytochrome P450-2D6 Screening Among Elderly Using Antidepressants (CYSCE)

Effects and Cost-Effectiveness of Pharmacogenetic Screening Among Elderly Starters With Antidepressants: A Pragmatic Randomized Controlled Trial

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 202 (actual)
• Sponsor: University of Groningen · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

Depression is common among elderly with an estimated prevalence of 5%. Due to ageing the national burden will double in the coming decade. Antidepressants as TCAs and SSRIs are effective in reducing symptoms, especially in people with severe depression. To optimize treatment efficacy and reduce side effects, the Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association developed guidelines for dose-adaptation, for instance for antidepressants such as nortriptyline and venlafaxine based on their main relevant genotype (CYP2D6) accompanied by Therapeutic Drug Monitoring. Such personalized drug dosing based on pharmacogenetic information at the start of therapy can speed up the titration phase of antidepressants to establish an adequate maintenance dose. However, pharmacogenetic screening programs are expensive and evidence on effects and costs of such a program among elderly antidepressant starters from randomized controlled studies is lacking. The investigators will conduct a pragmatic randomized controlled trial to determine the effects and costs of pharmacogenetic screening information to optimize drug dosing in depressed elderly patients who start with nortriptyline or venlafaxine. Objective: The primary objective is to determine the effects of pharmacogenetic screening for CYP2D6 on the time to reach adequate blood levels as an accepted proxy for adequate treatment. Secondary objectives include adverse drug reactions and cost-effectiveness Study design: pragmatic randomized controlled intervention study

Detailed description

This study is a multicenter randomized controlled trial in which psychiatric elderly care centers participate in the Netherlands. Deviating genotypes are expected to be found in \~30% of the population, therefore the study consist out of two parts. First a basic study in which \~750 patients, starting with nortriptyline or venlafaxine will be genotyped to identify patients with deviating genotypes (Poor, Intermediate or Ultrarapid Metabolizers). Second in the main study 150 patients with a deviating genotype are randomly allocated to two study arms one with and one without information on the genotype. From the extensive metabolizers('normal'genotype) 75 patients are allocated to a third arm as an external control.

Conditions

• Depression
• Depressive Disorder
• Poor Metabolizer Due to Cytochrome P450 CYP2D6 Variant
• Intermediate Metabolizer Due to Cytochrome P450 CYP2D6 Variant
• Ultrarapid Metabolizer Due to Cytochrome P450 CYP2D6 Variant

Interventions

Type	Name	Description
OTHER	Genotype information accompanied by a drug dosing advice	Dosing advices for deviating genotypes (Poor Metabolizer, Intermediate Metabolizer, Ultrarapid Metabolizer)based on the guidelines of the Royal Dutch Pharmacists Association (KNMP).

Timeline

• Start date: 2013-02-01
• Primary completion: 2017-05-01
• Completion: 2017-06-01
• First posted: 2013-01-29
• Last updated: 2017-08-18

Locations

11 sites across 1 country: Netherlands