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NCT Number: NCT01778907

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

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

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Key information

Conditions

Depression Behavior Behavioral Symptoms Depressive Disorder Intermediate Metabolizer Due to Cytochrome P450 CYP2D6 Variant Mental Disorders Mood Disorders Poor Metabolizer Due to Cytochrome P450 CYP2D6 Variant Ultrarapid Metabolizer Due to Cytochrome P450 CYP2D6 Variant

Age range

60 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

GGZ WNB, Halsteren, North Brabant, Netherlands

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Genotype information accompanied by a drug dosing advice

Other

Dosing advices for deviating genotypes (Poor Metabolizer, Intermediate Metabolizer, Ultrarapid Metabolizer)based on the guidelines of the Royal Dutch Pharmacists Association (KNMP).

Primary outcomes

  1. Serum drug levels of nortriptyline or venlafaxine

    Time frame: 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

    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.

Secondary outcomes

  1. Adverse drug events Questionnaire

    Time frame: 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

    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.

  2. Quality of life questionnaire

    Time frame: 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

    Quality of life will be assessed by the EQ5D questionnaire. This information will also be used for a cost-effectiveness analysis.

  3. Productivity Questionnaire

    Time frame: 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

    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.

  4. Self reported Severity of depression Questionnaire

    Time frame: 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

    Severity of depression by means of the QIDS-SR.

  5. Drug use

    Time frame: 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

    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.

  6. Data on health care associated resource use

    Time frame: 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

    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.

Sponsors and collaborators

Lead sponsor

University of Groningen

Other

Collaborators

  • ZonMw: The Netherlands Organisation for Health Research and Development

Registry information

Official study title

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

Acronym: CYSCE

Important dates

Study start
2013
Primary completion
2017
Study completion
2017
First posted
Jan 29, 2013
Registry last updated
Aug 18, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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