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

Overview

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 Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Single Group Assignment
  • Masking: Double (Investigator, Outcomes Assessor)
• Study Primary Completion Date: December 2014

Interventions

• Drug: Paroxetine
• Drug: Sertraline
• Drug: Citalopram
• Drug: Venlafaxine
• Drug: Amitriptyline
• Drug: Escitalopram
• Drug: Amitriptylinoxide
• Drug: Nortriptyline
• Drug: Trimipramine

Arms, Groups and Cohorts

• 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
• 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

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

• side effects
  • Time Frame: after 28 days of treatment
  • UKU side effect scale, AMDP side effect scale

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 79 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

• Lead Sponsor
  • HolsboerMaschmeyer NeuroChemie GmbH
• Collaborator
  • Max-Planck-Institute of Psychiatry
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Florian Holsboer, MD, PHD, Principal Investigator, Max-Planck-Institute of Psychiatry
• Overall Contact(s)
  • Barbara Breitenstein, MSc, 0049 89 30622, barbara_breitenstein@mpipsykl.mpg.de