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Completed

NCT Number: NCT03548675

Pharmacogenetics Informed Tricyclic Antidepressant Dosing (PITA)

Tricyclic Antidepressants (TCA's) are the cornerstone of treatment for patients with severe Major Depressive Disorder (sMDD). Current dosing is guided by repeated measurements of blood levels. Compared to patients with a normal metabolization function, for those with increased CYP450 enzyme activity it takes longer to reach a therapeutic drug level. The consequent delay of drug efficacy is associated with a prolonged treatment period, increased risk of suicidal behaviour and eventually lower remission rates. For those with reduced CYP450 activity higher rates of side effects are expected. An innovative TCA dosing strategy, taking the genetic variants of CYP2D6 and CYP2C19 into account may help to reduce the above mentioned problems. Up till now, the current guidelines for CYP450 pharmacogenetics based TCA dosing have not been systematically evaluated for effectiveness and cost-effectiveness in larger groups of patients. Such evaluation is necessary before broad implementation of these guidelines can be advocated. In the present study 200 patients with sMDD who are treated with nortriptyline, clomipramine or imipramine are randomized over two strategies: dosing based both on CYP450-genotype and blood level measurements and dosing as usual (standard doses plus blood levels). We hypothesize that genotype informed dosing results in faster attainment of therapeutic drug levels, lower rates of side effects, earlier symptom relief and lower levels of health- and working related costs.

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Key information

Conditions

Depressive Disorder, Major Depressive Disorder Mental Disorders Mood Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Radboudumc Dept of Psychiatry

Nijmegen, 6500 HB, Netherlands

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

Patients are in- and outpatients, having a primary diagnosis of severe major depressive disorder (SCID-I diagnosis in agreement with DSM-5 criteria and a Hamilton Rating Scale for Depression score ≥ 19 (HAM-D-17-item version), aged 18-65 years, who, according to their physician, are eligible for treatment with a TCA (Nortriptyline (NOR), Clomipramine (CLOMI) or Imipramine (IMI)). The choice of the specific TCA is at the discretion of the physician in attendance.

Exclusion criteria

  • Psychotic depression
  • Bipolar I or II disorder.
  • Schizophrenia or other primary psychotic disorder.
  • Drug or alcohol dependence in the past 3 months.
  • Mental Retardation (IQ < 80).
  • For women: pregnancy or possibility for pregnancy without adequate contraceptive measures.
  • Breastfeeding.
  • Serious medical illness affecting the CNS, including but not restricted to M Parkinson, SLE, brain tumour, CVA.
  • Relevant medical illness as contra-indication for TCA use, such as recent myocardial infarction.
  • Other drugs influencing the pharmacokinetics of the TCAs as based on a list of interacting drugs. In case of psychotropic co-medication only a benzodiazepine in a dose equivalent up to 4 mg lorazepam will be allowed.

Treatment and study plan

TCA treatment

Drug

All patients fulfilling inclusion criteria will be genotyped for CYP2C19 and CYP2D6 genes. Based on the genetic test results patients will be classified into a metabolisation phenotype (UM, EM, IM or PM).

Primary outcomes

  1. Time to TCA plasma concentration in the therapeutic range

    Time frame: During the 7 weeks treatment phase

    Time to TCA plasma concentration in the therapeutic range

Secondary outcomes

  1. Reduction of depressive symptoms

    Time frame: Difference between measurements at baseline and after 7 weeks of treatment

    HAM-D reduction

  2. Highest level of side effects

    Time frame: During the 7 weeks treatment phase

    summary measure: FIBSER

  3. Economic Evaluation (Cost Effectiveness)

    Time frame: 26 weeks after the start of treatment

    Utility based on EQ5D5L measurement

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Collaborators

  • ZonMw: The Netherlands Organisation for Health Research and Development

Registry information

Official study title

Pharmacogenetics to Improve Personalized Antidepressant Dosing in Patients With Severe Depression;a Randomized Controlled Trial Using Tricyclic Antidepressants

Acronym: PITA

Important dates

Study start
2018
Primary completion
2022
Study completion
2022
First posted
Jun 7, 2018
Registry last updated
Nov 29, 2022

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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