Optimizing Antidepressant Treatment by Genotype-dependent Adjustment of Medication According to the ABCB1 Gene
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- 25% improvement in the HAM-D
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: Paroxetine (Drug)
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
干预措施: Sertraline (Drug)
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
干预措施: Citalopram (Drug)
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
干预措施: Venlafaxine (Drug)
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
干预措施: Amitriptyline (Drug)
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
干预措施: Escitalopram (Drug)
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
干预措施: Amitriptylinoxide (Drug)
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
干预措施: Nortriptyline (Drug)
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
干预措施: Trimipramine (Drug)
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
干预措施: Paroxetine (Drug)
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
干预措施: Sertraline (Drug)
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
干预措施: Citalopram (Drug)
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
干预措施: Venlafaxine (Drug)
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
干预措施: Amitriptyline (Drug)
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
干预措施: Escitalopram (Drug)
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
干预措施: Amitriptylinoxide (Drug)
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
干预措施: Nortriptyline (Drug)
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
干预措施: Trimipramine (Drug)
结局指标
主要结局
25% improvement in the HAM-D
时间窗: after 28 days of treatment
Partial response indicated by at least 25% improvement in the Hamilton Rating Scale for Depression (HAM-D)
次要结局
- side effects(after 28 days of treatment)