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The ABCB1-gene product P-glycoprotein is an integral membrane protein that actively transports substrates out of the intracellular compartment. One of the major sites of its action is the blood-brain-barrier. It is highly expressed in brain capillary endothelial cells and involved in limiting the access of substrates such as antidepressants to the central nervous system. A single nucleotide polymorphism (SNP) of the ABCB1-gene was recently identified showing a different treatment response to antidepressant drugs depending on the genotype. Therefore, it is assumed that healthy subjects with different genotypes of that SNP will be associated with significantly different brain levels of the antidepressant escitalopram after 6 days of intake. Sleep recordings are a useful bio-marker for effects of antidepressants on the CNS. Selective serotonin reuptake inhibitors (e.g. escitalopram) cause a suppression of REM sleep and a stronger fragmentation of sleep compared to untreated subjects. Higher plasma levels of antidepressants affected the sleep to a greater extent than lower levels. In line with this finding, we suppose that sleep EEG recordings of healthy subjects with different genotypes of the above mentioned SNP will be differently affected after taking 6 days escitalopram. In addition, effects of drug intake on the gene expression in lymphocytes and metabolic changes will be assessed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Other | Healthy subjects with a single nucleotide polymorphism (SNP) of the ABCB1-gene (Genotype A) |
|
| 2 | Other | Healthy subjects with a single nucleotide polymorphism (SNP) of the ABCB1-gene (Genotype B) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| escitalopram | Drug | escitalopram 4 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time spent in rapid-eye-movement (REM) sleep assessed by polysomnography. | Time spent in rapid-eye-movement (REM) sleep assessed by polysomnography. | after 6 days of intake of escitalopram |
| Measure | Description | Time Frame |
|---|---|---|
| Sleep stages | Sleep stages beside REM sleep (wake, NonREM sleep) assessed by polysomnography | after 6 days of intake of escitalopram |
| Sleep continuity | Sleep continuity measures assessed by polysomnography |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Axel Steiger, MD | Max-Planck-Institute of Psychiatry | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Max Planck Institute of Psychiatry | Munich | 81667 | Germany |
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| ID | Term |
|---|---|
| D000089983 | Escitalopram |
| ID | Term |
|---|---|
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009570 | Nitriles |
| D001572 |
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| after 6 days of intake of escitalopram |
| ABCB1 gene expression | messenger ribonucleic acid (mRNA) expression of the target gene ABCB1 | baseline and after 6 days of intake of escitalopram |
| Metabolic changes | Small molecule metabolic changes in blood serum | baseline and after 6 days of intake of escitalopram |
| Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |