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

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

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

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).

Sponsors & Collaborators

• ZonMw: The Netherlands Organisation for Health Research and Development

  collaborator OTHER

• University of Groningen

  lead OTHER

Principal Investigators

• Bob Wilffert, Prof. Dr. · University of Groningen

• Eelko Hak, Prof. Dr. · University of Groningen

Study Design

Allocation

RANDOMIZED

Purpose

SCREENING

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-02-28

Primary Completion

2017-05-31

Completion

2017-06-30

Countries

• Netherlands

Study Locations