Pharmacogenomic Testing In Obsessive Compulsive Disorder by Carol Mathews, MD
Pharmacogenomic Testing for OCD is considered an adjunctive option, or something that could be added on to evidence-based care, with limitations. This article will teach you more about pharmacogenomic testing in general, and will remind you that there is not enough evidence at this time to know if it is helpful for OCD. There have only been one or two small studies of it in OCD, and they were too small to be conclusive.
Q: What is pharmacogenomic testing?
Pharmacogenomic (PGX) testing is a type of genetic testing that examines genes that that influence how a person metabolizes certain medications, as well as those that may influence response to certain medications. While PGX is a form of genetic testing, it does not assess all of a person’s genes. Instead, a small subset of individual genes that are known or thought to be important for drug metabolism or drug response are examined.
Pharmacokinetic (PK) testing
There are two major types of PGX testing. The first, and the most common, is pharmacokinetic (PK) testing, which examines genes involved in drug metabolism, or how the body processes or breaks down a particular medication or type of medication. This information can tell a healthcare provider whether someone is likely to have side effects from standard medication doses because they don’t metabolize it very effectively and thus, the medication builds up in their system.
Conversely, this type of test can also indicate whether someone metabolizes that medication faster than expected, which may make it less effective. The most common genes included in this form of PGX testing are the cytochrome (CYP) P450 genes, specifically CYP2D6 and CYP2C19. Depending on the drug, other genes may also be included.
Pharmacodynamic (PD) testing
The second form of PGX testing examines genes that are involved in how or where the medications are thought to work in the body. This is called pharmacodynamic (PD) testing. In principle, pharmacodynamic testing assesses how the person may respond to a particular medication, which in turn may tell a healthcare provider how effective the medication is likely to be. However, there is minimal evidence that PGX testing can accurately predict response of OCD to specific medications.
At this point, pharmacokinetic testing is much more common, and much better studied, than pharmacodynamic testing — although many direct-to-consumer companies offer this type of testing, the research behind this is not conclusive for most medications.
Q: How is PGX used in guiding treatment for a specific disorder?
PGX testing is used in clinical care before prescribing certain medications for specific illnesses or conditions. Some examples of medications that have PGX tests associated with their use include warfarin and clopidogrel, which are blood thinners, tamoxifen, which is used to treat breast cancer, and abacavir, which is a treatment for HIV.
In these instances, PGX testing can indicate whether a person is likely to have serious side effects from a particular medication, and in some cases, whether a person is likely to have a good response from that medication.
Q: Is pharmacogenomic testing useful in guiding medication treatment for psychiatric disorders?
A: The evidence for using PGX to guide medication treatment for psychiatric disorders is mixed. The US Food and Drug Administration (FDA) has identified several commonly used psychiatric medications for which PGX testing might be useful. However, the FDA also says that they do not necessarily advocate the use of PGX testing in everyone before prescribing these medications. Instead, they suggest that for the medications that they list, there is enough evidence to suggest that PGX testing may be useful in some cases.
They also say that healthcare providers should take into account a number of factors when deciding to prescribe a certain medication, and that PGX testing is only one of the many possibly important considerations.
The FDA makes recommendations regarding whether or how to use a medication when a given genetic variant is present. These recommendations are aimed at identifying people who, because of their genetic profiles, may be at increased risk of having serious side effects or adverse reactions if they take medication at the typically recommended doses. This information can be found on the medication package inserts and can also be found online.
The medications identified by the FDA as potentially having a PGX test that may help in guiding prescribing practices include aripiprazole (Abilify), amphetamine (which is in several commonly used medications for attention deficit hyperactivity disorder such as Adderall), atomoxetine (Strattera), brexpiprazole (Rexulti), carbamazepine (Tegretol), citalopram (Celexa), clozapine (Clozaril), Pimozide (Orap), thioridazine (Mellaril), venlafaxine (Effexor), and vortioxetine (Trintellix).
For all but two of these medications, the FDA recommends pharmacokinetic testing for the CYP2D6 metabolic pathway gene. In some cases, a different genetic test is recommended. For example, HLA-B testing is recommended before prescribing carbamazepine, and testing for the CYP2C19 gene is recommended for citalopram.
It is also important to note that for most psychiatric medications, there are no FDA recommendations for PGX testing, even for drugs that are also metabolized by the CYP2D6 or CYP2C19 genes. The reason for this is that while research is ongoing, for most psychiatric medications there is not yet clear evidence that PGX testing makes a difference in whether people will respond well to them or not, or whether they are more likely to have side effects.
This is also true for most of the medications that are on the FDA list — although there is some evidence that PGX testing may be useful for some people, there is not yet enough data to suggest that it will make a difference for most people.
For example, several studies have examined the use of PGX testing in major depressive disorder. Overall, the results of these studies are inconclusive, and do not provide strong evidence either in favor of using PGX testing or against using PGX testing.
One exception to this may be for people who have tried multiple (usually three or more) medications for depression and who have either not had a good result, or who have had multiple side effects. For these people, PGX testing may be useful in choosing an antidepressant with a lower risk of side effects. PGX testing may also be useful in determining what dose of a given medication may be needed to either see a response or to minimize the risk of side effects.
Q: Is PGX testing useful for OCD?
A: We don’t know the answer to this question yet, as there have only been one or two small studies of PGX testing in OCD, and they were too small to be conclusive. These studies did not show a difference in people with normal drug metabolism compared to those who metabolize OCD medications more slowly or more quickly than usual.
There was a suggestion in one study that people who did not metabolize these medications normally were more likely to have tried multiple medications to treat their OCD without success.
Q: Which psychiatric medications have a PGX test available?
A: Most of the medications that are used to treat psychiatric disorders have a PGX test available, as they are metabolized either by the CYP2D6 gene or by the CYP2C19 gene, which are included in almost all PGX panels. This includes the selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs) and other antidepressants, neuroleptics (also known as antipsychotics), and some, but not all, benzodiazepines.
Q: How can I get PGX testing?
If you would like to have PGX testing done, your healthcare provider will have to order it for you, as it is a laboratory test that requires a prescription. Some hospitals and laboratories offer their own PGX testing. Several direct-to-consumer companies also offer PGX testing for medications commonly used in psychiatric disorders, including SSRIs, other antidepressants, and neuroleptics.
Q: How does PGX testing get used by my healthcare provider to decide what medications I should take?
Most laboratories or hospital systems that offer PGX testing will also help your healthcare provider interpret the results and how to use them to guide your treatment. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has also published guidelines on how to interpret the results of PGX tests. These guidelines are publicly available and can be used by your healthcare provider to determine which medication and dose are right for you.
The direct-to-consumer companies typically report the results of their PGX testing panels in the form of a green/yellow/red message (or something similar), where green indicates that the medication can be used safely at standard doses, yellow means that the medication can be used, but caution and possibly altered doses are needed, and red means that the medication is not recommended for use by that person.
It is important to know that many direct-to-consumer companies also test PD genes, which have little or no evidence to support their use, and these genes are also included in the green/yellow/red recommendations. Therefore, while the green recommendation (OK to use as prescribed) is accurate on these panels, the yellow and red recommendations must be interpreted with caution, as they often exclude medications that might be beneficial.
If you do receive direct-to-consumer PGX testing, it is important to have someone who understands how to interpret the actual genetic results look over your tests rather than relying on the green/yellow/red recommendations. Your healthcare provider can also use the CPIC guidelines to interpret your genetic results and decide how best to incorporate them into your treatment.
Q: Is PGX testing covered by insurance?
Insurance coverage for PGX testing depends on the insurance and on the reason for testing. For most medications that are used for OCD, PGX testing is typically not covered by insurance, although there may be some exceptions.