Optimizing Antidepressant Treatment by Genotype-dependent Adjustment of Medication According to the ABCB1 Gene

HolsboerMaschmeyer NeuroChemie

Status and phase: Unknown; Phase 4

Conditions: Major Depression

Treatments: Drug: Escitalopram; Drug: Nortriptyline; Drug: Trimipramine; Drug: Venlafaxine; Drug: Amitriptylinoxide; Drug: Citalopram; Drug: Sertraline; Drug: Amitriptyline; Drug: Paroxetine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02237937

2011-003190-29

Details and patient eligibility

About

The study evaluates the ABCB1-genotype dependent efficacy of a quick dose-escalation strategy within 28 days of treatment with approved antidepressants that are known substrates of the P-glycoprotein, an efflux pump of the blood-brain barrier expressed by the ABCB1 gene.

Moreover, the study evaluates ABCB1-genotype dependent side-effects of approved antidepressants that are known substrates of the P-glycoprotein, an efflux pump of the blood-brain barrier expressed by the ABCB1 gene.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 79 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Male and female patients
• Age between 18 and 80 years
• Inpatients with a DSM-IV diagnosis of Major Depression
• single episode or recurrent
• moderate to severe intensity
• without psychotic features
• Inpatients with a DSM-IV diagnosis of bipolar disorder I or II
• current episode with depressive symptoms
• moderate to severe intensity
• without psychotic features
• HAM-D score at the time of inclusion in the study ≥ 14
• Patient has already been adjusted to one of the following antidepressants in a dose which is still under the defined normal-dose:
• paroxetine < 40 mg/d
• sertraline < 100 mg/d
• citalopram < 40 mg/d
• escitalopram < 20 mg/d
• venlafaxine < 225 mg/d
• amitriptyline < 150 mg/d
• amitriptylinoxide < 150 mg/d
• nortriptyline < 150 mg/d
• trimipramine < 150 mg/d

Exclusion criteria

• Acute suicidality (HAM-D Item 3 score > 2)
• Acute alcohol-, hypnotics-, analgesics- or psychopharmacological intoxication or delirium
• Current alcohol dependence, or dependencies from other psychotropic substances
• Severe medical or neurological diseases: patients with severe hepatic (severe impairment of liver function, cirrhosis of the liver), renal (kidney malfunctions), cardiovascular (recent myocardial infarction, instable heart disease), neurological diseases (e.g. multiple sclerosis, Parkinson, dementia)
• Patients incapable of giving informed consent
• Pregnant or breast-feeding women
• Women of reproductive age without effective contraception
• Simultaneous participation in other clinical trials or participation in an other clinical trial within 6 weeks before the start of the study
• Hypersensitivity to the study medication or to one of the ingredients of the medication
• Simultaneous treatment with another antidepressant besides study medication (exception: trazodone up to 75 mg/d, mirtazapine up to 15 mg/d, trimipramine up to 50 mg/d)
• Simultaneous treatment with mood stabilizers or neuroleptic drugs (exception: quetiapine up to 50 mg/d, olanzapine up to 5 mg/d)
• Exclusion criteria of the study medication

Trial design

80 participants in 2 patient groups

Normal dosage

Experimental group

Description:

Selected antidepressants that are substrates of the P-glycoprotein: Dosage: * paroxetine \< 40 mg/d * sertraline \< 100 mg/d * citalopram \< 40 mg/d * escitalopram \< 20 mg/d * venlafaxine \< 225 mg/d * amitriptyline \< 150 mg/d * amitriptylinoxide \< 150 mg/d * nortriptyline \< 150 mg/d * trimipramine \< 150 mg/d

Treatment:

Drug: Citalopram

Drug: Trimipramine

Drug: Venlafaxine

Drug: Amitriptylinoxide

Drug: Sertraline

Drug: Amitriptyline

Drug: Nortriptyline

Drug: Escitalopram

Drug: Paroxetine

High dosage

Experimental group

Description:

Selected antidepressants that are substrates of the P-glycoprotein: Dosage: * paroxetine \< 80 mg/d * sertraline \< 200 mg/d * citalopram \< 80 mg/d * escitalopram \< 40 mg/d * venlafaxine \< 450 mg/d * amitriptyline \< 300 mg/d * amitriptylinoxide \< 300 mg/d * nortriptyline \< 300 mg/d * trimipramine \< 300 mg/d

Treatment:

Drug: Citalopram

Drug: Trimipramine

Drug: Venlafaxine

Drug: Amitriptylinoxide

Drug: Sertraline

Drug: Amitriptyline

Drug: Nortriptyline

Drug: Escitalopram

Drug: Paroxetine