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:4/28/2016)... ... April 28, 2016 , ... The ... successful events, attracting medical professionals from around the globe who attended a week’s ... Opening Ceremonies Sunday, April 17 included the introduction of the 2016 ARRS Distinguished ...
(Date:4/28/2016)... Portland, Maine (PRWEB) , ... April 28, 2016 , ... ... of death and principal determinant of childhood mortality. This is particularly true in underdeveloped ... A lecture at the University of New England’s campus in Tangier, Morocco, will examine ...
(Date:4/28/2016)... ... April 28, 2016 , ... ... at VitaFoods 2016. , Nominated in the Healthy Ageing category, Cognizin® is being ... safety. The Healthy Ageing division can include everything from antioxidants, lipids, proteins, and ...
(Date:4/28/2016)... ... April 28, 2016 , ... The American Society for ... developers of the AnzuMedical™ Knowledge Sharing and Collaboration Platform™ , today announced ... platform is scheduled to launch in July 2016 and will be a combined ...
(Date:4/28/2016)... PA (PRWEB) , ... April 28, 2016 , ... ... Browne, M.D. has been named a Top Doc in Physical Medicine and Rehabilitation ... conjunction with Castle Connolly Medical, Ltd. by randomly surveying physicians and medical leadership ...
Breaking Medicine News(10 mins):
(Date:4/29/2016)... BERLIN , April 29, 2016 ... world-leading glyco-biology expertise, today announces the appointment of Dr. ... Dr. Zurlo is an oncologist with many years ... pharmaceutical and biotechnology industries. His last role was at ... Member of the Executive Board. Previously Dr. Zurlo held ...
(Date:4/29/2016)... 2016 Automation is one of ... to the growing demands for productivity in speed, accuracy, ... systems are already adept of a wide range of ... manual labor. Instrumentation continues to evolve, and is poised ... a few years ago. Originally used mostly by the ...
(Date:4/28/2016)... Mich. , April 28, 2016   ... . Diplomat Pharmacy, Inc. (NYSE: DPLO), the nation,s ... has signed a definitive agreement to acquire Valley ... Specialty Pharmacy ("TNH"), a leading specialty pharmacy that ... Van Nuys, California . In 2015, TNH ...
Breaking Medicine Technology: