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

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.

Study Overview

• Status: Unknown
• Conditions: Major Depression
• Intervention / Treatment: Drug: Paroxetine; Drug: Escitalopram; Drug: Sertraline; Drug: Amitriptyline; Drug: Citalopram; Drug: Venlafaxine; Drug: Nortriptyline; Drug: Trimipramine; Drug: Amitriptylinoxide

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Barbara Breitenstein, MSc; Phone Number: 244 0049 89 30622; Email: barbara_breitenstein@mpipsykl.mpg.de

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 80804
      • Recruiting
      • Max Planck Institute of Psychiatry
      • Principal Investigator: Barbara Breitenstein, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal dosage; 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; Drug: Escitalopram; Drug: Sertraline; Drug: Amitriptyline; Drug: Citalopram; Drug: Venlafaxine; Drug: Nortriptyline; Drug: Trimipramine; Drug: Amitriptylinoxide
Experimental: High dosage; 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; Drug: Escitalopram; Drug: Sertraline; Drug: Amitriptyline; Drug: Citalopram; Drug: Venlafaxine; Drug: Nortriptyline; Drug: Trimipramine; Drug: Amitriptylinoxide

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: HolsboerMaschmeyer NeuroChemie GmbH
• Collaborators: Max-Planck-Institute of Psychiatry
• Investigators: Principal Investigator: Florian Holsboer, MD, PHD, Max-Planck-Institute of Psychiatry

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: August 26, 2013
• First Submitted That Met QC Criteria: September 9, 2014
• First Posted (Estimate): September 12, 2014

Study Record Updates

• Last Update Posted (Estimate): September 12, 2014
• Last Update Submitted That Met QC Criteria: September 9, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Depression, Affective Disorder
• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Antidepressive Agents, Tricyclic; Cytochrome P-450 CYP2D6 Inhibitors; Adrenergic Uptake Inhibitors; Sertraline; Citalopram; Paroxetine; Amitriptyline; Venlafaxine Hydrochloride; Nortriptyline; Trimipramine
• Other Study ID Numbers: 2011-003190-29