Genetic testing for antidepressants - help or hype?

[bananas]

Two recent articles with very different perspectives.

http://www.marketwatch.com/story/this-test-is-changing-the-way-depression-is-treated-2016-02-17

This test is changing the way depression is treated

By Amy Hoak
Published: Feb 17, 2016 9:40 a.m. ET

<snip>

But a company in Mason, Ohio, is making advances in helping pinpoint the medicine best suited to an individual suffering from depression or another mental illness — by analyzing DNA swabbed from the inside of the patient’s cheek. The GeneSight test is based on technology licensed from the Mayo Clinic and Cincinnati Children’s Hospital Medical Center.

So far, 250,000 patients have been tested using GeneSight. Many commercial and government insurance plans — Medicare and the U.S. Department of Veterans Affairs included — cover all or part of the cost of testing.

<snip>

Recently, MarketWatch interviewed Virginia C. Drosos, Assurex’s president and chief executive, and Bryan M. Dechairo, the company’s vice president of medical affairs and clinical development. Below is an edited Q & A.

<snip>

MW: What type of patient is most likely to benefit from this test? Are there any patients who are less likely to benefit?

Drosos: GeneSight is appropriate for any person who did not respond to the medication prescribed to him or her for a mental health disease. After the first failed medication, only 29% respond to the second medication and only 17% respond on the third. At the same time, side effects go up. Anyone whose medication isn’t working or is taking multiple medications would significantly benefit from GeneSight. Also any people who have multiple or complex health conditions, children, or someone who is elderly.

MW: How successful is the test in pairing a patient with the best medication for him or her?

Drosos: When a doctor [prescribes] medication [he or she believes] is right for the patient, they only get it right 49% of the time the first time and 29% of the time the second time. When the doctor uses GeneSight for patients failing their current medication, we more than double the patient’s response rate to their new medication.

Dechairo: There’s no way that we will make the medications that exist today work for all patients, no matter how good our test is. Without GeneSight, only 1 in 4 patients [who are on their second medication] are getting better. We are making it 2 in 4. That’s a major improvement, but it’s not perfect. Antidepressants currently work through a few brain receptor pathways, including serotonin, norepinephrine, and dopamine. Mental health disorders occur through modulation of a constellation of neuro-networks which will require future molecular medicine discovery to effectively treat all patients.

MW: What is in the future for the company, and this field?

Drosos: We upgraded our test last November, going from 8 genes to 12 genes. We also added a significant number of medications in two new classes. We always had antidepressants and antipsychotics, and added anxiolytics [medications for anxiety] and mood stabilizers. This means that our Psychotropic [medicine that affects mental activity] panel is the most comprehensive available, covering more than 95% of the prescriptions written for depression, anxiety and bipolar disorder. We also have an Analgesic [pain killer] panel, which has broad coverage of medications used to treat chronic back pain, and an Attention Deficit Hyperactivity Disorder [ADHD] panel, which covers 100% of prescribed stimulant and non-stimulant medications. Our mission is to help patients with psychiatric, chronic pain and neurologic conditions achieve wellness, so we will keep expanding our treatment decision support products to achieve this as we make more scientific discoveries.

<snip>

http://necir.org/2015/10/03/more-harm-than-good-documentation/

More harm than good? Use of genetic mental health tests has grown rapidly. But evidence they work is scant. (+documentation)

By Beth Daley
October 3, 2015

RUTLAND, Vt. — For the first time in John R. Brown's two-decade quest for the right medication to make his brain behave, his psychiatrist offered him hope in the form of what seemed like rock-solid science.

By collecting the former editor's DNA with a quick cheek swab, a new genetic test retailing at $3,800 would reveal which depression medications Brown would likely respond well to and those he would not.

The GeneSight test result helped prompt Brown's psychiatrist to switch him to a new drug in June, making Brown optimistic that there might be a path back to a job, an apartment and even a new girlfriend. But three weeks later Brown, 40, was suicidal, checking into a mental hospital at his therapist’s urging.

"I can't help but wonder if I should have stuck with the devil I know," Brown now says.

<snip>

But a review by the New England Center for Investigative Reporting has found that virtually all the evidence that these psychiatric tests work is based on limited studies funded by the companies themselves or researchers they fund, including all five studies used to promote GeneSight on the company’s website.

The federal government doesn't require companies to prove thousands of tests are accurate before marketing and selling them. Unlike drugs, the Food and Drug Administration does not regulate them, although the agency has announced plans to.

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"It is the Wild West," said Mildred Cho, associate director at the Stanford Center for Biomedical Ethics, who says there is little published evidence on the effectiveness of drug response tests.

Eric Lander, a leader of the Human Genome Project and founding director of the Broad Institute in Cambridge, goes further, saying in a New England Journal of Medicine article earlier this year that the mental health testing company claims are "not harmless and may be quite dangerous."

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"The claims of these companies are weak," said Robert Klitzman, a psychiatrist and bioethicist at Columbia University who had a commentary published last week in a mental health journal calling for vigilance in the marketing of genetic mental health tests.

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Yet critics of these tests say it’s impossible for doctors — or anyone — to truly evaluate many of the tests. GeneSight’s proprietary formula for interpreting genetic information has never been independently assessed. The test examines genes well-known to play a role in antidepressant response, but it adds in others that do not have the same level of evidence, some researchers say.

Robert Howland, associate professor of psychiatry at the University of Pittsburgh, wrote a paper last year concluding that the makers of the GeneSight test have overstated the findings of their studies, making outside review more urgent.

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[Igel]

1. They should have edited the transcript more.

Not just remove the "uhs" and "ums".

(I'd note this is a standard kind of problem: When we think, we become dysfluent in speaking. Our foes we insist on being lightly edited at most because then we get to mock them. Our friends we insist on being highly edited because they're great and always grammatical and fluent. If the GeneSight spokesperson were a (R) candidate, we'd be mocking their inability to speak English grammatically. As soon as the spokesperson reverts to tried and true talking points, gets in a familiar groove, grammaticality increases because cognitive load decreases.

(I'd note that I did transcriptions for a while in-house at a non-profit, and once my boss insisted on an edited transcript. He wanted there to be no question about editing that might change, however slightly, his meaning. He came out of his office, red-faced, 10 minutes after I plopped the transcript on his desk. He insisted he did not, could not, would not ever speak the way the transcript said he did. So I pulled out the recording and he listened for the first few minutes, going from red-faced and angrily self-righteous to livid and furiously thwarted. He simply hadn't ever heard the dysfluencies in his speech, and those who focused on his train of thought also saw through the dysfluencies. Foes heard them; friends didn't notice them. He then asked me to revise the transcript, "lightly edit" is an appropriate description.)

[HuckleB]

2. A pharmacist's take: These tests are not ready for "prime time."

Genomic testing at your pharmacy: Ready for prime time?
https://www.sciencebasedmedicine.org/genomic-testing-at-your-pharmacy-ready-for-prime-time/

"Genomic testing isn’t routinely offered by your physician for a reason: At this time, its usefulness is not clear. Until better evidence emerges to demonstrate that genomic testing actually helps improve health, buying it from your pharmacy may do more harm than good. Genomic testing looks promising. But until its effectiveness has been validated, it’s probably best to seek out clinical trials, where you can help build the evidence base. There may as yet be an important role for pharmacists in the community to offer this testing. They are well positioned to guide advice to consumers (and other health professionals) on therapy decisions. But testing and advice needs to be offered when it’s useful to patient care – and not just when it supports a pharmacy’s bottom line."

[HuckleB]

3. A Test That Finds the Perfect Drug? Not likely.

http://www.theatlantic.com/health/archive/2015/05/a-test-that-finds-the-perfect-drug/393611/