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Genetic Tests Could Help Decide the Right Anti-depressants

Good news at hand for psychiatrists. And for patients too. Only the drug industry, those in marketing especially, might not be too very excited . Doctors may not have to fumble around switching from one anti-depressant to another hereafter. With a simple blood test, they will be able to characterize a patients unique genetic profile, determining what biological type of depression the patient has. Thereafter it should be relatively easy to figure out which antidepressant is likely to work best.

With hit-or-miss approach gone, doctors may have little time entertaining the nattily clad representatives of drug manufacturers. Scientists have identified genetic variations that affect specific neurotransmitter functions, which could explain why some patients respond to some drugs but not to others.

For example, some depressed patients respond quickly to selective serotonin reuptake inhibitors (SSRIs), which relieve depression, in part, by flooding the brain with serotonin. Serotonin is a hormone that transmits nerve signals between nerve cells and also causes blood vessels to narrow. Changes in the serotonin levels in the brain can alter the mood. Hence the rationale in using drugs containing serotonin in countering depression.

Now only those who have abnormally low levels of serotonin may respond to SSRIs. Yet others may have an abnormality in other neurotransmitters that regulate mood, like norepinephrine or dopamine. SSRIs could have no impact on them. In a report last October in the journal Science, Dr. Francis Lee identified a genetic mutation that could potentially predict patients responses to an entire class of antidepressants.

He inserted into a mouse a defective variant of the human gene for brain-derived neurotrophic factor, a protein that is increased in the brain with SSRI treatment and is critical to the health of neurons. Then he subjected these humanized mice to stress and found that they did not respo nd to Prozac with decreased anxiety. The clear implication is that people with this variant will not be able to respond to any SSRI, which requires normal neurotrophic-factor function to work.

A psychiatrist could identify this genetic variant and then steer his patient to a different class of antidepressants. Furthermore, other genes may play a role in the adverse effects of antidepressants that have made recent headlines: suicidal behavior. Recent evidence shows that a small number of depressed adolescents and young adults experience an increase in suicidal feelings and thoughts when they are treated with SSRIs, compared with a placebo.

It is entirely possible that a genetic variation in one or more genes that regulate serotonin function makes these people feel briefly more suicidal, rather than less, when exposed to the drugs. This new field of pharmacogenomics will also enable psychiatrists to predict which drugs might produce toxic side effects for certain patients. Nearly all drugs are metabolized by a group of enzymes that vary greatly in activity from person to person.

If patients have a genetic mutation that results in either deficient enzyme activity or none, they would be likely to have serious side effects if exposed to the drug that is metabolized by the enzyme. Within a few years, patients could be routinely screened for these genetic variations, which will tell a doctor which drugs to avoid. This could potentially prevent unnecessary drug toxicity, a major cause of illness and death.

Aside from the potential to transform clinical psychiatric practice, these new developments will surely change the relationship between doctors and the drug industry and between the industry and the public. Direct-to-consumer advertising will become nearly irrelevant because the drugs will no longer be interchangeable, but will be prescribed based on an individuals biological profile.

Likewise, docto rs will have little reason to meet with drug company representatives because they wont be able to give doctors the single most important piece of information: which drug for which patient. For that doctors will need a genetic test, not a salesman. Soon, your psychiatrist will really get to know you not just your mind, but your brain, too. Treatment doesnt get more personal than that.


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