Pharmacogenetics Informed Tricyclic Antidepressant Dosing (PITA)

Phase 4

Completed

• Conditions: Depressive Disorder, Major
• Interventions: Drug: TCA treatment

• Registration Number: NCT03548675
• Lead Sponsor: Radboud University Medical Center

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2018-05-23
• Study First Submitted: 2018-05-23
• Study First Submitted QC: 2018-06-06
• Study First Posted: 2018-06-07
• Primary Completion: 2022-02-02
• Study Completion: 2022-07-13
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-28
• Last Update Posted: 2022-11-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 125

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.

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Exclusion Criteria

1. Psychotic depression
2. Bipolar I or II disorder.
3. Schizophrenia or other primary psychotic disorder.
4. Drug or alcohol dependence in the past 3 months.
5. Mental Retardation (IQ < 80).
6. For women: pregnancy or possibility for pregnancy without adequate contraceptive measures.
7. Breastfeeding.
8. Serious medical illness affecting the CNS, including but not restricted to M Parkinson, SLE, brain tumour, CVA.
9. Relevant medical illness as contra-indication for TCA use, such as recent myocardial infarction.
10. 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Genotype-guided TCA treatment	TCA treatment	Genotype guided dosing of the TCAs in patients with a PM,IM,EM or UM phenotype based on pharmacogenetic test.
Standard TCA treatment	TCA treatment	Standard dosing of TCA in patients with a PM,IM, EM or UM phenotype based on pharmacogenetic test

Primary Outcome Measures

Name	Time	Method
Time to TCA plasma concentration in the therapeutic range	During the 7 weeks treatment phase	Time to TCA plasma concentration in the therapeutic range

Secondary Outcome Measures

Name	Time	Method
Economic Evaluation (Cost Effectiveness)	26 weeks after the start of treatment	Utility based on EQ5D5L measurement
Reduction of depressive symptoms	Difference between measurements at baseline and after 7 weeks of treatment	HAM-D reduction
Highest level of side effects	During the 7 weeks treatment phase	summary measure: FIBSER

Trial Locations

Locations (1)

Radboudumc Dept of Psychiatry; 🇳🇱 Nijmegen, Netherlands