Debunking the Myths Surrounding Genetic Testing for Psychiatric Medications
In recent years, psychiatric care has joined other medical specialties in the quest for personalized medicine. Genetic testing is being marketed as a game-changing resource for predicting how well a patient will respond to a psychiatric medication, based on that certain components of that individual’s unique genetic code. This approach, a function of the medical science known as pharmacogenomics—the study of how genes influence a person’s response to drugs—holds the promise of tailoring treatment plans to the genetic profiles of individual patients, as it has already in the area of cancer treatment. Despite this promise however, experts and research organizations have consistently expressed concern about the current utility and validity of the practice in psychiatry, noting numerous limitations and advising a cautious approach, or, as the American Psychiatric Association has advised, avoiding these tests altogether as being as yet not adequately develop for psychiatry [1].
Genetic Testing for Psychiatric Medications: An Introduction
The concept is compelling in its simplicity: Genetic testing for psychiatric medications is heralded as the epitome of personalized precision medicine, whereby the use of genetic information to guide the selection of medications is believed to lead to treatment regimens that are more likely to succeed. The test results could ostensibly save the patient and clinician from the potentially long and painful process of giving a medication 4-6 weeks to work and then tapering off, only to switch to a different medication and start the process all over again if the medication fails. However, the reality is significantly more complex, and the relative effectiveness of such tests is far from a given [2].
The Science Behind the Skepticism: Lack of Proof
Despite the growing interest in using genetic tests to guide treatment with psychiatric medications, a confluence of scientific and commercial factors has created a dearth of well-validated tests and left many patients and providers in an information vacuum. The example of antidepressants is illustrative. The FDA has specifically warned against using genetic tests to guide the choice of antidepressants because “the relationship between DNA variations and the effectiveness of medication has not been established.”
The FDA went further, warning that the use of gene-drug pairs in this way might lead to “inappropriate treatment” of patients that could cause “serious adverse health effects or death.”
Research studies have produced inconsistent results regarding the ability of genetic tests to predict how individuals with psychiatric conditions will respond to a variety of psychotropic medications. The causes of these inconsistent results are multiple and complex. Mental health disorders are complex, nutritionally influenced, environmentally impacted conditions that are the result of numerous genetic, environmental and personal experiential factors. Genomic testing cannot determine if a person has a psychiatric disorder; if they do, which disorder it is; or—most importantly—which medications work most effectively for them even though marketing materials make it seem this is what they do. Furthermore, because of their spectrum nature, psychiatry patients almost always have multiple psychiatric “disorders” that blend into one another with fuzzy boundaries, meaning their genetic profile is immensely complex, making it exceedingly difficult to definably match specific medications with a patient.
Indeed, at this time, genetic testing for psychiatric conditions does not actually test for the condition itself but rather for a single or handful of jeans that are responsible for breaking down a given medication. This means that the tests for the most part can only determine whether a high or low dose of the medication will produce side effects, saying nothing about its efficacy.
What makes identifying the genetics of psychiatric conditions so challenging is that are predicated upon not a single or nor handful of genes, but rather gene networks that run into the hundreds of mutually interacting genes, with different conditions sharing many of the same genes and blending clinically into each other. The prospect of actually testing for the condition and matching it to the medication is going to require very much more research then in those cases in the rest of medicine where single genetic variations can be matched to a given medication protocol. Indeed, it requires an entirely different approach to diagnosis than the rigid categories of the DSM.
Two observations:
First, the network structure of the genetic background to psychiatric conditions is analogous to the network structure of symptoms. However there is not a one-one-one correspondence between a gene and a symptom–they are different networks altogether though based on a similar principle that orders many different levels of biological systems.
Second, you can see directly whether looking at the gene network or the symptom network that a spectrum model of diagnosis emerges naturally in contrast to the black and white diagnostic “boxes” that we are familiar with. In fact, this familiar rigid categorical structure of diagnosis was known to be inaccurate in the 1950’s when it was developed for the first DSM (Diagnostic and Statistical Manual). It was deliberately imposed firstly to make psychiatric diagnosis look more like diagnosis in the rest of medicine and secondly because the makers of the DSM thought the true, spectrum, model would be too confusing for people. This decision has caused many more problems than it has solved–and most people in fact intuitively understand that the boxed categories are not correct. Fortunately, is slowly being dismantled by research necessities.
Currently marketed genetic testing for psychiatric medications looks at one or few genes, and in most cases these are not even the genes that underlie the condition being treated, but the metabolic genes (e.g., governing liver function) that break down medication either quickly or slowly. There are research projects underway that do look at the gene network structure, and all its huge number of individual variations, and the correlation of the network variations to medication response, but as you might imagine looking at the network example above, the task of translating this into medical decision-making for an individual is still far off.
The Limits on Genetic Testing for Psychiatric Medications
Professional Stance
Due to their many limitations, the American Psychiatric Association (APA) and the Food and Drug Administration (FDA) are among the many organizations that have cautioned against the use of genetic testing for psychiatric medication selection [1]. A more comprehensive approach to the use of genetic information consists of evaluating all the genetic, environmental and lifestyle information along with the clinical symptoms of psychiatric disorders of an individual. The best genetic information actually comes from the family history, including, if available, medications that have been effective for first or second degree relatives.
Marketing May be Misleading
Despite these limitations, genetic tests are being aggressively marketed to prescribers of medication, to specialists, to general practitioners, and to the public, and are leaving some patients with an implicit impression that the tests definitively forecast which medications are best for them. Disillusion on the one hand, or else exaggerated belief on the other hand, ensue when the tests, simply by chance, proves either incorrect or correct—a distortion either way. Insurance companies such as Blue Cross Blue Shield and Anthem have likewise established that the tests show a “lack of compelling evidence of the medical necessity of the test” and that these tests “do not improve health outcomes.” Like other research techniques that have been brought to market prematurely, these tests are therefore also costly.
Comprehensive Evaluation is Paramount
Experts advocate a comprehensive review of symptoms, titration of medication doses, and consultation with one or more subspecialists (e.g. a clinical psychiatrist, and/or a child psychiatrist) as more fruitful alternatives to genetic testing. Such professionals should have extensive psychopharmacologic training–to know the recipes and algorithms well–and experience–to know when and how to go beyond. The Sterling Institute finds that true mental health optimization comes from a multi-disciplinary approach. In short the Sterling Institute feels a combination of psychiatry, pharmacology and psychotherapy can yield the best outcomes.
The Future of Genetic Testing in Psychiatry
Potential for Personalized Medicine
Although the current evidence doesn’t support the widespread use of genetic testing in the selection of psychiatric medications, there is a future where that won’t be the case. The technology involved is always improving. When reliable tests emerge, ones that prove to play an important role in customizing psychiatric treatment, the psychiatrists at Sterling Institute, with strong research backgrounds, will deploy them immediately
In Summary …
The Sterling Institute offers a comprehensive range of neuropsychiatric, psychotherapeutic, and mind-body services and prides itself on taking a scholarly and humanistic approach to patient centered care. For those who are researching treatment options for various mental health conditions, Sterling Institute offers the perfect place to start to ensure results that are truly the best achievable.