childhood, Mandy E. has struggled with feelings of
hopelessness and inadequacy. She seemed incapable of having
fun. She experienced what she described as "constant
parents felt it was a matter of the will to fix the problem;
they didnít accept the possibility of mental illness.
a year ago, Mandy, 24, a marketer for a Boston e-commerce
startup (she asked that her full name be withheld) sought
psychiatric help. "I needed to do something because I
wanted to move my life in a certain direction, and I felt I
wasnít going to do that if I didnít get help," she
Dr. Mindy Rosenbloom, a psychiatrist in Barrington, R.I., who
practices near Mandyís hometown.
a clinical assistant professor at Brown University, diagnosed
Mandy with dysthymia, a mild but persistent form of
depression. The psychiatrist, who specializes in hard-to-treat
cases, said finding the right anti-depression drug is a
complicated process that can take months, even years. In Mandyís
case, Rosenbloom simplified the trial-and-error process with a
doctor turned to cotton swabs and DNA testing to personalize
her recommendations for Mandy. She used the swabs to collect
Mandyís cheek cells and sent them for DNA extraction and a
genomic scan to Assurex Health, a precision medicine startup
based in Mason, Ohio, "to identify the antidepressant
medication options Mandy would tolerate best and would most
likely respond to."
approach is an emerging field known as pharmacogenomics, or
Food and Drug Administration in recent years has recognized
the power of pharmacogenomics and lists known genetic factors
on package inserts for 137 medications, including several
dozen for psychiatric conditions such as depression and
anxiety. (For a list of the drugs with warnings, go to .)
Mark Dunnenberger, who runs the Pharmacogenomics Clinic at
NorthShore University HealthSystem, in Chicago, one of the
first clinics in the U.S. dedicated to interpreting the
effects DNA has on drugs, said inroads are being made in the
field. The process is to analyze the individualís ability to
metabolize anti-depression and antipsychotic medicines as well
as medicines to treat arthritis, heart disease, infectious
disease, lung disease, cancer and many other conditions.
we inherit eye and hair color from our parents, we inherit
genes that determine how our bodies respond to medicines,
especially genes used to break down drugs in the liver,
kidneys and other organs. Genes are the bodyís manuals that
determine how we respond individually to drugs.
genomics differ, doctors generally have taken a
one-size-fits-all approach to prescribing meds, taking into
consideration age, sex and weight while overlooking growing
evidence of differences based on genetic inheritance.
NorthShore clinic, in Evanston, Ill., collects
pharmacogenomics data on psychiatric illnesses and other
conditions to incorporate the information in the patientís
electronic medical record.
said genomic testing is not a panacea but it helps reduce
guesswork: Drugs that likely wonít work can be avoided, and
doses can be adjusted based on the individualís genomic
need to help our patients understand pharmacogenomics can be
helpful to them when they get certain medications but not
every medication," he said. "And we can discuss cost
and risk of getting genetic information and wrap that up
handful of personalized companies extract DNA from cheek swabs
or saliva samples and compare genes with findings in medical
literature of how gene mutations affect the bodyís ability
to metabolize medicines.
Health, the company that processed Mandyís DNA sample, uses
technology licensed by the Mayo Clinic in Rochester, Minn.,
and by Cincinnati Childrenís Hospital, with financial
backing from Sequoia Capital, the Silicon Valley venture
capital firm behind Google, Airbnb and PayPal.
GeneSight line of tests specializes in psychiatric and
neurological disorders. Competitors offer broader
pharmacogenetic testing, which includes psychiatric
Mamiya, director of pharmacy at Seattle-based Genelex Corp.,
noted that more than 75 percent of the population has genetic
variations that determine how their bodies process and use
drugs. "This applies not only to prescription medications
but also to over-the-counter medicines, herbal and dietary
supplements, and recreational drugs such as marijuana,"
the pharmacist said.
had three tests. One was GeneSight Psychotropic, a
pharmacogenomic test involving the analysis of 50 markers from
six genes and a clinical outcomes-based tool that weighs the
influence the markers have on 32 different agents. A second
was Genesight ADHD for determining drugs to use for attention
deficit hyperactivity disorder. The third, MTHFR, tested her
ability to process folate, a B vitamin. If insufficiently
metabolized, folate can result in deficiencies of three brain
chemicals that antidepressants use.
received the report in a few days with a traffic signal-style
list of medicines, a strategy typically used by testing
listed under green can be used as directed. Those in the
yellow category should be used with caution. Those in the red
category should be used with increased caution and more
frequent monitoring. Additional notes explain whether higher
or lower doses are indicated, whether the patientís genes
may reduce efficacy of meds or whether a drug simply should be
said testing reduces but doesnít eliminate trial and error.
She said Mandy "felt tired all day" during the first
days on a green-zone medicine and has felt well on a red-zone
option, Wellbutrin XL (bupropion), prescribed at the lowest
dose to compensate for her much slower than average metabolism
of that drug.
significantly, testing showed Mandy had a single mutation in
the MTHFR enzyme critical in metabolizing folate found in
foods or vitamin supplements. Researchers showed in the 1960s
that folate deficiency could trigger depression. Genetic
testing can reveal enzyme mutations linked to commonly
consumed drugs and vitamins.
gave Mandy a prescription form of processed folate, l-methylfolate,
that can cross the blood-brain barrier and switch on enzymes
that would help her metabolize antidepression medicines such
as Wellbutrin. "The rest is history. Mandy applied for
and obtained a full-time job in Boston and has been commuting
and doing well," she said.
panels are not cheap. GeneSight Psychotropic, Assurexís most
commonly prescribed test, lists for $3,800, which Don Wright,
executive vice president and chief operating officer of
Assurex Health, said is comparable to that for many other
that multiple studies have shown the testing on average saves
patients $2,500 per year in prescription costs and reduced
number of medical office and emergency room visits. Patient
co-insurance responsibility for bills is typically 10 percent
to 20 percent for commercial insurance, while Medicare and
Medicaid patients have no out-of-pocket expense.
said her familyís Blue Cross plan covered all but $6 of the
testing. Insurance coverage varies.
James Evans, a medical geneticist at the University of North
Carolina and editor-in-chief of Genetics in Medicine, the
official journal of the American College of Medical Genetics
and Genomics, is bullish on genomics. He even has a DNA tattoo
on his shoulder.
has been skeptical about pharmacogenomics, even as President
Barack Obama gave the field a boost in his 2015 State of the
Union along with the promise of a $215 million investment and
a genomic study of more than a million Americans.
pharmacogenomics is well-established for cancer but is on
shaky ground in many areas, such as testing for the
anti-clotting drug Coumadin (warfarin). "The public
clamors for astrology, too. Itís just not a good reason to
offer a medical test," he said. "Some of it is snake
oil." Evans examined the research Assurex Health has
sponsored and was impressed that the researchers are
"publishing in peer-reviewed journals and going about
collecting evidence in the right way."
Rosenbloom said pharmacogenomics is dramatically changing
psychiatric practice. She said psychiatric patients
traditionally were, in effect, "guinea pigs" as they
tried out a variety of medications in a variety of doses.
were limited criteria to help us select medications," she
said. "Personalizing psychiatric prescriptions based on
DNA makes pharmacology safer, better tolerated, improves
patient adherence and the likelihood of their response to the
medications we prescribe."