Some people find that the first medication they try delivers great results: their depression lifts, they feel more like themselves, and they have few or no side effects. But for many others, finding the right medication is a frustrating exercise in trial and error.
What if a simple test could tell you what medication is right for you? Right now, such a test doesn’t exist. But as we report in Harvard Medical School’s updated special health report, Understanding Depression, researchers are uncovering which genes influence mood and finding out how they function. The hope is that these discoveries will make it possible to test who has what kind of depression, perhaps eliminating some of the guesswork involved in prescribing antidepressants.
In effect, depression may be many diseases, not a single one. Scientists have found that dozens of genes affect mood, and as our genetic endowments differ, so do our depressions. That may be more apparent when symptoms differ—for example, when one person experiences depression as profound sadness and another primarily feels listless and takes pleasure in nothing. But even when symptoms are similar, the underlying causes may vary—and thus the same drug that works marvelously for one person may have little effect on another.
If gene- and protein-based work being done in labs today fulfills its promise, future patients will receive different medicines for different types of depression. Researchers are pursuing the goal of targeting medication more effectively, one “snip” at a time. A snip, or SNP, is a single nucleotide polymorphism; these are small variations in the DNA sequence that can lead to big differences in biological function.
An example is the SNP code-named G1463A. People with G1463A produce very low levels of serotonin, a neurotransmitter that helps regulate mood. This aberrant SNP shows up more often in people who have major depression than those who don’t. And depressed people with G1463A are relatively resistant to SSRI antidepressants like Prozac and Zoloft, which act on serotonin. Some day doctors may be able to test for this variant to determine whether an individual is a good candidate for treatment with an SSRI or if another medication is a better fit.
In 2008, scientists discovered another gene variation that seems to influence how well patients respond to treatment. People who have certain variations in the TREK1 gene are more likely to have treatment-resistant depression, meaning that they failed to respond to at least one and sometimes many different medications.
Not only is current research adding to our understanding of why people respond differently to antidepressants, it’s also paving the way for blood tests that can help your doctor track how well you are responding to a medication. Scientists have discovered that levels of a protein called beta-arrestin-1 are low in depressed people, but return to normal after treatment with an antidepressant. One day, doctors may be able to monitor a patient’s progress on a given treatment by measuring levels of this protein.
These kinds of tests are not yet realities, but in the years to come, it’s likely that today’s scientific discoveries will significantly reshape how depression is treated.
Have you been reading about genetic research in depression? What reports have interested you? What do you think of these advances?
Dr. Michael Miller has been on staff of the Beth Israel Deaconess Medical Center, a large teaching hospital in Boston, for more than 25 years. He is also an Assistant Professor of Psychiatry at Harvard Medical School.
Depression
Nearly 1 in 10 adults will suffer from some form of depression in a given year, affecting not only them, but also their friends and family. Thankfully, years of research and recent breakthroughs have made this serious illness easier to treat. With Understanding Depression, a special health report from Harvard Medical School, you can stay up-to-date on the latest information on depression symptoms and treatments to improve your life—or the life of somseone close to you.
Are you Living With Depression? Connect with others with similar health concerns and issues. Click here to join the group.
This content is not intended to substitute for personalized medical advice, diagnosis, or treatment from your healthcare provider. Read our full disclaimer.
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Comments: 11
Thanks for writing -- your experience is very common. It is a trial and error business now and we all hope the science will help us predict better which treatment will work with the fewest side effects.
Keep us posted on how that goes -- vagus nerve stimulation is an interesting treatment.
Thanks for telling us about your experience. It can be terribly frustrating to bear with trials of antidepressants — especially if the results are disappointing or the side effects too much to take. Given the current state of the art, you would almost have to try every antidepressant on the market for several weeks each to figure out the best balance of positive and negative effects.
And — even if you had the time and patience for that process — you would have to keep track of the results, which isn’t so easy.
But a systematic approach like that can work. If you and your doctor take notes about your experience, you might be able to find the treatment that works best for you.
In the end, I completely agree — being able to test in advance will be an amazing improvement on what we have now.
and other who died in shock treatment, I was certain there was a connection. I'm glad that it is being researched.
I would love it if we could measure our serotonin and other hormone levels and adjust medications accordingly.
Additionally to have the ability to test before medication therapy to determine what medications would work best would be incredible. I have been on almost every SSRI on the market and am finally showing results with Lexapro after almost 10 years of trying different medications and combinations of medications.