Are The Answers in Our Genes?!

In psychiatric care, finding the right medication can be a slow and sometimes frustrating process. When pharmacogenetic testing first became available, there was understandable excitement about the prospect of a personalized approach based on an individual’s unique genetic makeup. However as pharmacogenetic testing became more common, it became clear to clinicians the necessity for a clear-eyed assessment of the clinical value and limitations of this emerging technology. The resulting investigations have led to some dampening of the initial promise and confusion among parents, patients, and clinicians about how best to use testing as it exists today. This article aims to review the nuts and bolts of pharmacogenetic testing, as well as the current evidence and guidelines for its use.

To start, it is important to clarify the terminology of genetic tests. “Genetic testing” is an umbrella term used for two main types of tests – diagnostic and pharmacogenetic:

• Diagnostic testing attempts to identify specific disorders based on an individual’s genetic profile. In psychiatry, this is mainly focused on identifying developmental/genetic disorders related to intellectual disability and autism spectrum disorder such as Down Syndrome and Fragile X Syndrome.

• Pharmacogenetic testing attempts to understand how an individual may react/respond to a medication. This is available primarily through private direct-to-consumer/clinician companies such as Genesight, Genomind, and Assurex (amongst many others). This article will be focusing on this type of testing.

How does pharmacogenetic testing work?

• Pharmacogenetic testing analyzes an individual’s genetic makeup (“genotype”) at clusters of genes related to how a medication acts in the body. The hope is to use this information about an individual’s genetic profile to make better and more personalized decisions when prescribing medication.

Wait, so can this tell me what medication I (or a loved one) will respond to?

• The simple answer is no. Pharmacogenetic testing has yet to be proven to reliably predict what response (or therapeutic effect) a person will have to a particular medication. There has yet to be an established connection between genetic variations at the genes that are tested and a medication’s effects.

Ok, so what CAN it tell us then?

• As it exists currently, pharmacogenetic testing can help guide clinicians with how to dose SOME medications for SOME people. By identifying genetic variations of the enzymes involved in the metabolism and/or action of certain medications, the testing categorizes individuals as either a poor, intermediate, or rapid metabolizer, with each category carrying a different clinical implication.
• For example: a “slow metabolizer” has a less active enzyme and therefore may break down a medication more slowly. This might encourage a clinician to take a more “low and slow” approach than is standard in this individual, as they may be more sensitive to side effects and/or require lower doses to experience a positive effect.

Are there any risks of pharmacogenetic testing?

• There are no known significant direct physical/medical risks of taking a genetic test. However, given that the utility and consistency of these tests remains in question, there is a risk of using these tests inappropriately. If these tests are used to make decisions in lieu of or to override established clinical evidence regarding efficacy, this may result in an individual receiving treatment that is not evidence-based and does not meet the standard of care.
• Currently, there are no tests authorized by the FDA to predict response/adverse effects of a specific medication. Additionally, studies have shown that the results can vary between companies (Bousman CA et al, Pharmacogenet Genomics 2017;27(11):387–393).

What are the current recommendations on the use of these tests?

• The majority of mental health/medical governing bodies and organizations including the APA, AACAP, IGPA, and FDA currently recommend against the use of pharmacogenetic testing as part of the standard psychiatric evaluation/treatment process (see below for links to each).
• There are certain situations where testing can/should be considered. These include:
• Multiple failed medication trials
• Unusual responses and/or adverse effects to medications
• Very specific clinical scenarios such as the initiation of carbamazepine in an individual of Asian descent

Takeaways:

• Pharmacogenetic testing can be useful in certain situations, but is not currently recommended as part of routine, evidence-based psychiatric care.
• Do not change or stop medication based on a genetic test completed on your own and please speak to your clinician if you are considering pharmacogenetic testing to make the most informed decision that matches your needs and goals.
• The field of genetics is continually evolving and we are learning more every day. While not currently recommended, the hope is that pharmacogenetic testing will eventually be used as part of standard personalized medical and mental health care as the technology develops further.

Resources/Guidelines:

• American Psychiatry Association (APA) guidelines
• American Academy of Child and Adolescent Psychiatry (AACAP) guidelines
• International Society of Psychiatric Genetics (ISPG) Statement on Testing
• FDA Safety Communication on Pharmacogenetic Testing