Olivia Bentley, PharmD, AAHIVP, CFTS

Pharmacogenetics has the potential to radically change the practice of psychiatry. Since the advent of psychopharmacology, psychiatrists and pharmacists have struggled with a set of baffling treatment outcomes: so-called idiosyncratic drug reactions, drug sensitivities, or, conversely, patients who require high doses of medication for a modest clinical benefit. As the science of pharmacogenetics has emerged over the past several years, professionals are now beginning to understand why some people in the real world react to medications far differently than clinical trial data would suggest.

Those who work in this field can see a future in which psychotropics are tailored to the patient; indeed, many findings can be applied in clinical practice right now. Other pharmacogenetics applications are not quite ready for standard care, and patients with mental health disorders may be filling in our knowledge gaps with misinformation. Pharmacists can play a key role in helping patients navigate this new world of psychopharmacogenetic testing.

Misconceptions: Separating Marketing from Science

It is encouraging that patients are increasingly aware of pharmacogenetics. They proudly proffer their red light/yellow light/green light reports to their psychiatrists and pharmacists. Unfortunately, some patients who make use of these reports are being provided too little education along with the results, leading to unrealistic expectations or misperceptions. This result is troublesome.

It is common for these patients to believe that pharmacogenetics testing can identify the perfect drug for them—a truly tailored treatment. The future may indeed hold that promise, but that is not the current reality. Psychiatrists, pharmacists, and patients can learn a great deal from pharmacogenetics testing; however, that report will not magically reveal the ideal medicine for a specific patient. It is important that psychiatrists and pharmacists help patients understand their results, especially when the results come from direct-to-consumer pharmacogenetic testing. Professionals can use test results as an opening to educate patients, and to clarify misconceptions.

Challenges: More Complex than a Stoplight

The red, yellow, and green light reports may seem like a simple way to describe pharmacogenetics results, but many patients seem to apply their own interpretation, especially in the absence of professional counseling and education. This can interfere with quality mental health care.

Without proper counseling, many patients believe that “green” medications are perfectly safe, "yellow" medications should be used only under dire circumstances, and "red" medications should be avoided at all costs. In some circumstances, a green medication may be a terrible choice for a specific patient, a yellow medication may be completely innocuous, and a red medication may be helpful, as long as the patient is given a very low dose or is willing to undergo periodic blood monitoring. Quite frequently, patients will fail to achieve a satisfactory clinical response from their first, second, or third medication trial. However, patients often are reluctant or even refuse to consider a “red” medicine because of misconceptions about what it means. This can shut the door to a potentially beneficial medication, perhaps the 

The stoplight reporting is not inherently flawed. In fact, it can be a useful starting point to discuss these issues with patients. However, the red/yellow/green reporting schema is not as straightforward as it may seem to patients (or some professionals). As with other laboratory results, imaging studies, or professional consultations, the information provided should be considered in context, and by a professional. Because pharmacists have deep training and expertise in pharmacokinetics, pharmacodynamics, and pharmacogenetics, they are in the ideal position to help patients look past the simple stoplight color coding and truly customize the details provided in the reports. Moreover, educating patients may improve patient adherence, which is key to success in psychiatric treatment.

Successes: How Pharmacogenetics Is Used in Psychiatry Today

While fully personalized psychiatry is still in the future, many current applications exist for pharmacogenetics in psychiatry practice. One example that arises quite commonly is in the management of patients who require antipsychotic medications, particularly aripiprazole and risperidone. People who are poor cytochrome P450 2D6 (CYP2D6) metabolizers will typically have substantial increases in circulating drug concentrations and area under the curve (AUC) on these medications. Pharmacogenetic testing of CYP2D6 can help determine if the initial and target dosage of certain antipsychotics should be lowered (eg, halved).

 (Aripiprazole and risperidone are also excellent examples of potentially “red” medications that can be safely and effectively dose adjusted.)

Consider the common situation of a 13-year-old boy diagnosed with ADHD and bipolar disorder. The treatment plan included psychostimulants and a second-generation antipsychotic, in this case, aripiprazole. The standard starting dose is 5 mg orally daily. After a week on aripiprazole, the boy experienced terrible nausea, akathisia, and sedation. On the other hand, his manic symptoms improved. Of course, when he refuses to take the medication because of the adverse effects (AEs), the manic symptoms return. Pharmacogenetics testing later revealed that the boy was a slow CYP2D6 metabolizer. The patient eventually agreed to take the medication at a dose of 2.5 mg. At the lower dose, the boy’s symptoms were well managed by the medication and it was well tolerated.

Pharmacogenetics testing may also assist in an opposite circumstance, such as when a patient is an ultra-rapid metabolizer, breaking down the active molecule at a higher-than-normal rate, making for lower-than-expected blood levels of the drug. Standard prescribed dosages, even at the high end of the recommended dosage range, may yield sub-therapeutic drug levels in ultra-rapid metabolizers.

Pharmacogenetics testing also informs antidepressant use. Tricyclic antidepressants (TCAs), for example, fell out of favor as selective serotonin reuptake inhibitors (SSRIs) gained prominence. The latter drug class generally has fewer serious AEs than the former. However, TCAs still play an important role in certain conditions, for certain patients. Pharmacogenetics testing can provide an explanation for why some people experience certain AEs while taking TCAs (eg, anticholinergic effects), and this information can be used to guide management decisions.

 Incidentally, we are tantalizingly close to being able to use polymorphisms in serotonin transporters and receptors to determine whether patients are more or less likely to respond to a specific antidepressants class.

These are just 2 examples of pharmacogenetic testing in modern clinical psychiatry. These results can also help guide the use of stimulants, mood stabilizers, and anxiolytics.

When pharmacogenetics testing is performed judiciously and interpreted thoughtfully, it can be a powerful tool to maximize treatment response and tolerability of medications commonly used to treat mental health disorders. Some pharmacogenetic results can be applied in psychiatric practice today, and many more will become the standard of care by the end of this decade. The pharmacist is ideally suited to help patients and clinicians navigate this emerging and important field so that findings are correctly interpreted and put into a clinical context. As pharmacists perform medication therapy management or other clinical consultations with a patient, they may be instrumental in identifying and educating patients who can benefit from pharmacogenetic testing. The overall outcome is greater treatment efficacy, fewer AEs and drug interactions, and improved medication adherence.

Dr. DelBello received funding for research from NIMH, NIDDK, PCORI, Eli Lilly, Assurex Health, Pfizer, Johnson and Johnson, Otsuka, Sunovion, Lundbeck, and Shire, and has served as a consultant for Sunovion, Neuronetics, Pfizer, Lundbeck, Takeda, and Supernus.

Dr. Olivia Santoso Bentley is a leader of the Pharmacogenetic Center of Excellence and clinical pharmacist consultant to the Rxight Pharmacogenetic Program.

Melissa P. DelBello, MD, MS, is a professor of psychiatry and pediatrics, and the Dr. Stanley and Mickey Kaplan Professor and Chair of the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine. Olivia Bentley, PharmD, AAHIVP, CFts, has advanced training and certification in pharmacogenetics and precision medicine.

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Articles

Pharmacogenetics has the potential to radically change the practice of psychiatry.

Pharmacogenetics in Psychiatry: Misconceptions, Challenges, and Successes

The top 5 causes of emergency hospitalizations due to adverse drug events are warfarin, insulin, oral antiplatelets, diabetes medications, and opioid pain medications.

 With the exception of insulin, science has shown how genetic implications in an individual’s metabolism influence the safety and efficacy of all of these medications. How many of the millions of adverse drug reactions and hospitalizations could be prevented if patients were consistently put on the right drug and the right dose based on their genetic makeup, and, importantly, avoided medications that were ineffective or put them at increased risk of an adverse drug event? As medication treatment becomes more proactive and personalized, pharmacists have a unique opportunity to play a vital role on the health care team through clinical application of pharmacogenetic information in patient care.

Pharmacogenetic testing is more than getting a cheek swabbed and seeing the results. Once patients know they are CYP2D6 ultrarapid metabolizers, what is next? Well, like normal individuals, they go to “Dr. Google.” What if, based on their Internet search, they discontinue all their medications that are affected by CYP2D6? Also, remember that pharmacogenetics is just one piece of the puzzle.

There are drug-drug interactions, liver and kidney function, and environmental factors to consider, as well. What if these patients were on a medication that inhibited CYP2D6? What would be the appropriate course of action then? This is called phenoconversion, which is when an individual’s genotypic phenotype differs from his or her observed phenotype due to nongenetic extrinsic factors, such as drug-drug interactions.

For precision medicine, pharmacists need to consider drug-drug-gene interactions, as well. These are the questions and concerns that arise when the medical community is asked about how pharmacogenetic information could be safely and ethically delivered to the community. Pharmacists have always been the medication experts dealing with drug-drug interactions on a daily basis. Now, with the new tool of pharmacogenetics, we can become the drug-druggene experts, as well.

As a profession, we have a responsibility to our patients to always be at the forefront of education and knowledge about medications and how they work in the body. As the most accessible (first-line) health care providers in our communities, pharmacists must have a solid understanding of this complex science in order to use the right language with patients and to clarify misconceptions and avoid misuse of this information. Most important, pharmacists should ensure coordination of care with patients’ medical providers to ensure that this information does not go to waste. By showing patients the potential impact of their genetic profile, pharmacists will truly have an impact on the lives of their patients and reduce avoidable health care costs.

Pharmacists can serve as a pharmacogenetic resource for medical providers. As most medical clinics may be short on clinical staff and have limited genetic counselors, pharmacists can become a tremendous resource and support for medical providers.

Pharmacists are ideal for disseminating pharmacogenetic information to patients who see multiple medical providers and specialists. Because all patients are encouraged to use 1 pharmacy, it can become the ideal center for housing patients’ pharmacogenetic information. Pharmacists are already intervening in drug-drug interactions from multiple providers; therefore, it seems fitting that pharmacists intervene when patients are placed on new medications with a pharmacogenetic implication, while also taking into account other inducers and inhibitors on patients’ profiles.

“Retailer” stigma is one of the challenges that the pharmacy profession faces when stepping into pharmacogenetics or any clinical role. The general public and, sometimes, the medical community may only see a pharmacist as someone behind a counter whose sole purpose is to put medications into bottles. We know the truth, but what are we doing in our daily practice to reveal it to our patients and other health care professionals? A grassroots movement does not start with Congress or legislation. It starts with each of us in our daily practice.

In the model we propose for best practices for the safe and ethical delivery of pharmacogenetic information, the prescriber is engaged from the outset, patients are counseled on their results by a pharmacist trained in pharmacogenetics, and pertinent findings are coordinated with patients’ medical providers. Pharmacy-dispensing software systems and electronic health records have started integrating patients’ pharmacogenetic information to alert a pharmacist or a medical provider with clinical decision support.

It is vitally important that pharmacists get involved in the field of pharmacogenetics. Direct-to-consumer pharmacogenetic testing has been stopped by the FDA, as this kind of testing puts patients at risk. The more we can avoid patient dependence on “Dr. Google” for answers to health care questions, the better. Pharmacists’ knowledge and accessibility to medical providers and to communities will bring value to precision medicine. The roles of pharmacists in all settings are shifting. As our profession takes on more clinical roles, we have a responsibility to our patients and to medical providers in our communities to be a knowledgeable and reliable medication resource, which increasingly includes pharmacogenetics.

Dr. Amina Abubakar and Dr. Olivia Santoso Bentley are the leaders of the Pharmacogenetic Center of Excellence and clinical pharmacist consultants to the Rxight Pharmacogenetic Program.

Amina Abubakar, PharmD, AAHIVP, has advanced training and certification in pharmacogenetics and precision medicine, is the owner of Rx Clinic, and has received the following honors: 2012 PDS Pharmacist of the Year, 2015 PDS Entrepreneur of the Year, 2014 Independent Pharmacy Leader, and 2014 NCAP Award for Excellence In Innovation. Olivia Bentley, PharmD, AAHIVP, CFts, has advanced training and certification in pharmacogenetics and precision medicine and has received the following honors: 2015 PDS Team Leader of the Year and 2016 Next-Generation Rising Star Pharmacist Finalist.

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