Navigation Links
Genetic difference predicts antidepressant response
Date:1/23/2008

Researchers have identified subtle genetic variations that predict the efficacy of two widely used antidepressant drugs. They found that certain variants in the gene for a protective transporter protein that pumps drugs and other substances out of the brain compromise the effectiveness of the antidepressants citalopram (trade name Celexa) and venlafaxine (Effexor).

The researchers said their findings indicate that genetic testing could help predict the responses of patients to particular antidepressants. More broadly, they said, such tests could help predict the efficacy of any drugs used to treat neurological disease.

Manfred Uhr and colleagues published their findings in the January 24, 2008, issue of the journal Neuron, published by Cell Press.

Antidepressants are the first-line treatment for major depression, but their overall clinical efficacy is unsatisfactory, as remission occurs in only one-third of the patients after a trial with an adequately dosed single drug, and remission rates further decline following successive treatment failures, wrote the researchers. This situation is particularly alarming in view of the fact that major depression constitutes one of the greatest disease burdens worldwide and is anticipated to be the second leading global disease burden by the year 2020, trailing only cardiovascular disease.

One reason for such poor response rates, said the researchers, is that protective transporter proteins pump such substances as drugs and some hormones back into the bloodstream, preventing them from crossing the blood-brain barrier.

In their studies, the researchers explored the function of one such transporter protein, called P-gp, in preventing the entry of antidepressants into the brain. They first knocked out genes for the transporter protein in mice and administered the antidepressants to the animals. The researchers found that brain concentrations of citalopram and venlafaxine were regulated by P-gpthat the antidepressants were thus substrates of the transporter.

Studying 443 patients on the antidepressants, they next searched for variants in the human gene that correlated with reduced efficacy of the drugs. Their genetic analysis identified 11 such variants.

To our knowledge, our results provide for the first time evidence that genetic variants in the [gene for P-gp] account for differences in the clinical efficacy of antidepressants, most likely by influencing their access to the brain, they wrote.

The general conclusion to be drawn is that any drug administered to treat CNS diseases should be analyzed for its P-gp substrate status, which can be determined by using knockout mice. From a clinical point of view, the findings warrant that patients receiving a drug that is a P-gp substrate for the treatment of brain diseases are genotyped to exclude the possibility that a patient receives a drug that fails to enter the CNS to an extent required for efficacy.

The researchers also suggested that development of future antidepressants should take into account whether the candidate drugs are transported by P-gp. And, clinical trials of antidepressants should be designed to take into account the P-gp genetic status of patients in the trial.


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related medicine news :

1. Genetics May Determine Antidepressants Effectiveness
2. Genetics Influence Blood Pressure Medications
3. Lupus in women: New genetic risk factors identified
4. Scripps research scientists find new genetic mutation that halts the development of lupus
5. Genetic Mutations Boost Prostate Cancer Risk
6. People with anorexia less likely to be blamed when biology, genetics explained
7. Years-Long Search Unlocks Deadly Genetic Disease
8. Brain imaging and genetic studies link thinking patterns to addiction
9. Human genetic variation -- Sciences Breakthrough of the Year
10. Top10 research advances include studies on genetics and stem cell research, stents
11. Twins study shows genetic basis for face and place recognition
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... ... Quality metrics are proliferating in cancer care, and are derived from many ... the beholder, according to experts who offered insights and commentary in the current issue ... the full issue, click here . , For the American Society of Clinical ...
(Date:6/26/2016)... , ... June 26, 2016 , ... PawPaws brand ... new product that was developed to enhance the health of felines. The formula is ... The two main herbs in the PawPaws Cat Kidney Support Supplement Soft ...
(Date:6/25/2016)... ... June 25, 2016 , ... ... and applications at AcademyHealth’s Annual Research Meeting June 26-28, 2016, at the Hynes ... important health care topics including advance care planning, healthcare costs and patient and ...
(Date:6/25/2016)... California (PRWEB) , ... June 25, 2016 , ... "With ... fit their specific project," said Christina Austin - CEO of Pixel Film Studios. ... customizable and all within Final Cut Pro X . Simply select a ProHand ...
(Date:6/25/2016)... ... June 25, 2016 , ... Dr. Calvin Johnson has dedicated ... has implemented orthobiologic procedures as a method for treating his patients. The procedure ... doctors to perform the treatment. Orthobiologics are substances that orthopaedic surgeons use to ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... June 24, 2016 Research and Markets ... for Companion Diagnostic Tests" report to their offering. ... Companion Diagnostics The World Market for Companion ... medicine diagnostics. Market analysis in the report includes the following: ... (In Vitro Diagnostic Kits) by Region (N. America, EU, ROW), ...
(Date:6/24/2016)... , June 24, 2016  Arkis BioSciences, a ... invasive and more durable cerebrospinal fluid treatments, today ... The Series-A funding is led by Innova Memphis, ... and other private investors.  Arkis, new financing will ... and the market release of its in-licensed Endexo® ...
(Date:6/23/2016)... June 23, 2016 Research and ... Excipients Market by Type (Organic Chemical (Sugar, Petrochemical, Glycerin), ... Topical, Coating, Parenteral) - Global Forecast to 2021" ... The global pharmaceutical excipients market is projected ... CAGR of 6.1% in the forecast period 2016 to ...
Breaking Medicine Technology: