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

Depression Clinical Trial

— CYSCE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01778907
• Other study ID #: RUG11003
• Status: Completed
• Phase: Phase 4
• First received: January 22, 2013
• Last updated: August 15, 2017
• Start date: February 2013
• Est. completion date: June 2017

Study information

• Verified date: August 2017
• Source: University of Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 202
• Est. completion date: June 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• Major depression according to DSM-IV (296.2x, 296.3x) criteria for which the treating psychiatrist decided to start drug treatment with either nortriptyline or venlafaxine.

• Competent to understand the informed consent procedure

Exclusion Criteria:

• Use of clinically relevant CYP2D6 inhibitors

• Use of clinically relevant CYP2D6 inducers

• Use of other drugs that affect plasma levels as co-medication

• Serious hepatic failure

• Patients for which drug treatment with venlafaxine is started and a GFR < 30 ml/min.

• Patients with the very rare genotype: Intermediate Metabolizer with duplications (IMDUP).

Related Conditions & MeSH terms

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

Intervention

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).

Locations

Country	Name	City	State
Netherlands	Jeroen Bosch Ziekenhuis	's-Hertogenbosch
Netherlands	Reinier van Arkel groep	's-Hertogenbosch
Netherlands	GGz inGeest	Amsterdam
Netherlands	Parnassia	Den Haag
Netherlands	GGZ Centraal	Ermelo
Netherlands	Lentis	Groningen
Netherlands	University Medical Centre Groningen	Groningen
Netherlands	GGZ WNB	Halsteren	Brabant
Netherlands	GGZ-NHN	Heiloo
Netherlands	GGZ Friesland	Leeuwarden
Netherlands	Isala Klinieken	Zwolle

Sponsors (2)

Lead Sponsor	Collaborator
University of Groningen	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum drug levels of nortriptyline or venlafaxine	Serum drug levels will be assessed by 'dried blood spot' analysis, blood will be obtained by a fingerprick.; Adequate serum drug levels is defined as: serum drug levels within the therapeutic window (for nortriptyline 50-150 µg/L, for venlafaxine 200-400 µg/L in combination with stable drug dosing for at least 3 weeks.	After 2, 4 and 6 weeks treatment started, after the 6th week sampling continues every 2 weeks untill adequate serum drug level is reached with an expected average of 8 weeks
Secondary	Adverse drug events Questionnaire	Adverse drug events will be assessed by a self-reported questionnaire (ASEC). Two different questionnaires will be used, one for the side-effects of venlafaxine and another one for nortriptyline. Both are based one the ASEC questionnaire.	At start of treatment and from that moment on, every 2 weeks untill adequate drug serum levels are reached with an expected average of 8 weeks
Secondary	Quality of life questionnaire	Quality of life will be assessed by the EQ5D questionnaire. This information will also be used for a cost-effectiveness analysis.	After 2, 4 and 6 weeks treatment started and if adequate serum drug levels are not reached in 6 weeks, every 2 weeks, untill adequate serum drug levels are reached with an expected average of 8 weeks
Secondary	Productivity Questionnaire	Effects on productivity by means of the Short Form-Health and Labour Questionnaire, part Labour. This information will also be used for a cost-effectiveness analysis.	After 2, 4 and 6 weeks treatment started and if adequate serum drug levels are not reached in 6 weeks, every 2 weeks, untill adequate serum drug levels are reached with an expected average of 8 weeks
Secondary	Self reported Severity of depression Questionnaire	Severity of depression by means of the QIDS-SR.	After 2, 4 and 6 weeks treatment started and if adequate serum drug levels are not reached in 6 weeks, every 2 weeks, untill adequate serum drug levels are reached with an expected average of 8 weeks
Secondary	Drug use	Drug use, including exact dosing and duration of prescription will be assessed by self reported drug use by the patient. This information will also be used for a cost-effectiveness analysis.	At inclusion, after 2, 4 and 6 weeks after inclusion and if adequate serum drug levels are not reached in 6 weeks, every 2 weeks, untill adequate serum drug level is reached with an expected average of 8 weeks
Secondary	Data on health care associated resource use	Data on health care associated resource use (e.g. visits to the specific specialists including diagnoses; drug use including exact dosing and durations of prescriptions; hospitalizations, inclusive exact intensities of care; and lab values if relevant). This information will also be used for a cost-effectiveness analysis.	After 2, 4 and 6 weeks treatment started and if adequate serum drug levels are not reached in 6 weeks, every 2 weeks, untill adequate serum drug levels are reached with an expected average of 8 weeks