Genetic test could match mentally ill patients with the best drug

Genetic test could match mentally ill patients with the best drug


The new test will assess whether 26 psychiatric drugs ? including Prozac ? are likely to work or cause side-effects

http://www.timesonline.co.uk/tol/life_and_style/health/mental_health/article7078157.ece


Mark Henderson, Science Editor 1 Comment

Recommend? (3) A genetic test that predicts how patients with mental illnesses such as depression and schizophrenia will respond to drugs is to be offered to British doctors, in a step towards a new era of personalised medicine.



The £1,000 procedure, which is already used in several US hospitals, uses individuals’ DNA to assess whether 26 psychiatric drugs — including Prozac and Seroxat — are likely to work or cause side-effects.



It promises to bring significant improvements to the care of patients with psychiatric conditions, at least a third of whom do not currently benefit from the first drug they are prescribed because they cannot tolerate it or it has no effect.



The development highlights the growing potential of genetics to tailor treatment according to patients’ DNA profiles. This practice, known as pharmacogenetics or pharmacogenomics, is expected to transform many branches of medicine over the next decade, helping doctors to select the therapy that works best for a particular patient.




The psychiatric DNA test, known as GeneSightRx, is offered by the US company AssureRx, which plans to introduce it in Europe by the end of the year.



It is intended for patients who have already proved difficult to treat but could eventually be used by GPs before they prescribe anti-depressants. British experts agreed that such tests could have significant benefits, but cautioned that while the science behind GeneSightRx is sound, there is little evidence yet that it improves patient outcomes.



Peter McGuffin, Professor of Psychiatric Genetics at the Institute of Psychiatry in London, said: “There’s a lot of promise here, and in the long run pharmacogenomics will work, but it’s complex.



“We need evidence that these tests provide an advantage over practice as usual, and in my view that hasn’t been done yet. There is sound science underlying this, but the practicalities have not been looked at in nearly enough detail.”



Donald Singer, Professor of Clincial Pharmacology and Therapeutics at the University of Warwick, said: “At the sharp end of psychiatry, when people are having suicidal thoughts, you really have to get the drug right at the beginning, and a test like this could be very helpful.



“The technology is there, but clinical evidence is the stumbling block: we need to investigate the human element of how it is used and whether it affects patient outcomes.”



Pharmacogenomic tests are founded on the understanding that variations in DNA alter the way that individuals respond to medicines.



Some genes influence the speed with which drugs are metabolised: too fast and a patient may get no benefit, too slow and levels can build up to cause side-effects. Other genes affect the biological receptors on which drugs are designed to work, so that some peoplelack the ability to respond.



GeneSightRx uses a cheek swab to collect DNA, after which five genes are analysed. These are CYP2D6, CYP2C19 and CYP1A2, which affect metabolism, and SLC6A4 and 5HTR2A, which affect serotonin, the brain-signalling chemical on which many psychiatric drugs work. The test was developed by scientists at the Mayo Clinic in Minnesota and Cincinnati Children’s Hospital in Ohio, and is in standard use at both hospitals.



It sorts antipsychotics and antidepressants into three colour-coded groups. A green code indicates drugs that should be safe to use normally, yellow denotes drugs that should be used “with caution”, and red highlights greater risks.



Jim Burns, President of AssureRx, said: “It’s a tool to guide doctors to a medication that might be a better choice for that patient, or to make a dosage adjustment. It is mostly about identifying patients at risk for extreme side-effects: if you cannot tolerate a drug, it will not be useful.”



Caroline Wright, head of science at the PHG Foundation, a genetics think-tank, said the results would be important.“The question is whether such tests improve clinical practice. We don’t yet know whether this actually helps doctors to find the best drug, or whether it’s easier just to try out several different treatments.”



Majorie Wallace, chief executive of the mental health charity SANE, said: “It would be marvellous if there were a way of identifying those people who responded well to certain psychotropic drugs while avoiding giving particular drugs to those for whom it may not be effective or cause distressing side-effects.”



Tailored for a better fit



Warfarin Two genes, CYP2C9 and VKORC1, affect response to the blood-thinning drug given to heart attack and stroke patients. DNA tests can be used to adjust dosage to ensure patients benefit while avoiding potentially fatal bleeding



Abacavir About 6 per cent of people have a gene that makes them hypersensitive to this HIV drug. DNA screening is now recommended before use



Codeine About 10 per cent of Caucasian people have a version of the CYP2D6 gene that means they cannot process the painkiller, and thus derive no benefit



Statins The SLC01B1 gene influences risk of muscle damage while on the cholesterol-lowering drugs. Scientists are investigating whether genetic factors affect which statin is most likely to work



Cancer drugs About 1 in 300 people lacks the gene to metabolise the leukaemia drug 6-mercaptopurine, and thus risk fatal side-effects. Cancer drugs such as Herceptin and Iressa are also tailored to target particular genetic mutations in tumours



Source: Francis Collins, The Language of Life; Times database