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

Study Overview
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Brief Summary
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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.

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

Conditions
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Major Depression

Intervention / Treatment
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* Drug: Paroxetine
* Drug: Sertraline
* Drug: Citalopram
* Drug: Venlafaxine
* Drug: Amitriptyline
* Drug: Escitalopram
* Drug: Amitriptylinoxide
* Drug: Nortriptyline
* Drug: Trimipramine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal dosage<br>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 | Drug: Paroxetine<br> <br> Drug: Sertraline<br> <br> Drug: Citalopram<br> <br> Drug: Venlafaxine<br> <br> Drug: Amitriptyline<br> <br> Drug: Escitalopram<br> <br> Drug: Amitriptylinoxide<br> <br> Drug: Nortriptyline<br> <br> Drug: Trimipramine<br> <br> |
| Experimental: High dosage<br>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 | Drug: Paroxetine<br> <br> Drug: Sertraline<br> <br> Drug: Citalopram<br> <br> Drug: Venlafaxine<br> <br> Drug: Amitriptyline<br> <br> Drug: Escitalopram<br> <br> Drug: Amitriptylinoxide<br> <br> Drug: Nortriptyline<br> <br> Drug: Trimipramine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 25% improvement in the HAM-D | Partial response indicated by at least 25% improvement in the Hamilton Rating Scale for Depression (HAM-D) | after 28 days of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| side effects | UKU side effect scale, AMDP side effect scale | after 28 days of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Affective Disorder