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:5/26/2017)... ... May 26, 2017 , ... Amir Qureshi, MD is ... powerfully versatile, patient-centric spinal cord stimulation system. The Nuvectra™ Algovita SCS System has been ... pleased to be the first in Arkansas to introduce the most powerful SCS system ...
(Date:5/26/2017)... ... May 26, 2017 , ... Boar’s Head Brand®, one of ... Memorial Day entertaining that are sure to satisfy your guests’ flavor cravings, while ... and cheeses featured in these refreshingly balanced recipes are packed with flavor, creating ...
(Date:5/26/2017)... ... May 26, 2017 , ... After raising nearly $30,000 on Kickstarter ... to be available at a discounted crowdfunding price on Indiegogo . , “Along ... I also wanted to bring a fidget toy to the market that was made ...
(Date:5/26/2017)... ... May 26, 2017 , ... Rob Lowe acts as host and ... the series is on hiking in American. Viewers can reconnect with America as it ... of hiking. , Many consumers have looked for an inventive new place for a ...
(Date:5/26/2017)... ... , ... “THE FLINTHILLS FAMILY-Our Journey to the Cross”: the personal journey of Bob Massey and ... creation of published authors, Bob and Margaret Massey. Bob Massey is small in stature ... and leather tough." His love for others is apparent in all of his life ...
Breaking Medicine News(10 mins):
(Date:5/18/2017)... May 18, 2017  Two Bayer U.S. Pharmaceutical leaders ... during its recent 28 th Woman of ... event showcases HBA,s longstanding mission of furthering the advancement ... Cindy Powell-Steffen , senior director of ... division, and Libby Howe , a regional business ...
(Date:5/15/2017)... Inc., a privately-held CNS pharmaceutical company based in ... disease (PD), has enrolled the first patient in the RASMET ... study involving patients with PD and taking place at 12 ... period. The first stage is open label and involves single ... Denver , Boca Raton ...
(Date:5/10/2017)... Hologic, Inc. (Nasdaq: HOLX ) announced today ... ended April 1, 2017 .   GAAP diluted earnings ... the prior year period as the sale of the ... non-GAAP diluted EPS of $0.50 increased 6.4%.  Revenue of ... terms.  Excluding the effects of blood screening and the ...
Breaking Medicine Technology: