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

Condition(s) targeted: Major Depression

Intervention: Paroxetine (Drug); Sertraline (Drug); Citalopram (Drug); Venlafaxine (Drug); Amitriptyline (Drug); Escitalopram (Drug); Amitriptylinoxide (Drug); Nortriptyline (Drug); Trimipramine (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: HolsboerMaschmeyer NeuroChemie GmbH

Official(s) and/or principal investigator(s):
Florian Holsboer, MD, PHD, Principal Investigator, Affiliation: Max-Planck-Institute of Psychiatry

Overall contact:
Barbara Breitenstein, MSc, Phone: 0049 89 30622, Ext: 244, Email: barbara_breitenstein@mpipsykl.mpg.de

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Investigator, Outcomes Assessor)

Primary outcome: 25% improvement in the HAM-D

Secondary outcome: side effects

Minimum age: 18 Years. Maximum age: 79 Years. Gender(s): Both.

Criteria:

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

Barbara Breitenstein, MSc, Phone: 0049 89 30622, Ext: 244, Email: barbara_breitenstein@mpipsykl.mpg.de

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

Starting date: September 2011
Last updated: September 9, 2014