What is Pharmacogenetic Testing?
And how does it help in the management of depression
There are many aspects of antidepressants that makes them challenging to prescribe, the complicating aspects are:
- They take weeks for their effect to be felt
- They cause side effects almost immediately, these side effects may be intolerable, such that some drop the drug before it becomes effective. Most side effects are temporary and can be managed until the drug becomes effective. Unfortunately, most healthcare providers do not pay enough attention to this fact, resulting in drug failure due to side effects intolerance and not drug efficacy.
- There are many genetic hurdles that could cause a medication to fail for a patient, so a pharmacogenomics test is very important to ascertain the most compatible medication. Side effects are also a genetic variable
- Some patients can build tolerance to some antidepressants i.e., they work for a while then stop working. This is also a genetic variable.
Pharmacogenomics testing is NOT a commodity or a mere transaction, is a complex SERVICE.
To determine the most compatible antidepressant for a patient, the pharmacogenomics service must include:
- Testing for metabolic genes to ensure the drug can achieve the optimal concentration in the blood
- Testing for the blood brain barrier protein to ensure entry of the drug into the brain
- Testing for brain receptors that are the various antidepressant’s targets
- And most importantly, the service must include the services of a specially trained psychopharmacist who will:
- Interpret the results of the three components of the test and provide an antidepressant treatment plan, including tapering the existing antidepressant/s, and titrating the recommended antidepressant/s,
- Will advise on expected side effects, prepare the patient to manage them and will be available in the event of unexpected side effects.
- The pharmacist might include some adjunct medication that may be necessary.
Metabolic genes (pharmacokinetics)
Drug metabolism refers to chemical processes that facilitate the rate at which a given liver enzyme can clear a drug from the system. Metabolism may also refer to the conversion of a pro-drug into its’ biologically active metabolite or substance via liver enzyme.
Most anti-depressants are cleared by CYP2D6, and a few by CYP2C19.
- Some patients are normal metabolizers, which means that the normal dose should work for them.
- Some patients are poor metabolizers, that means the drug is not cleared from the blood sufficiently, that will cause severe side effects, so avoidance or reduction of the dose is a must.
- Some patients are rapid metabolizers, which means the drug is cleared from the blood rapidly such that the drug is ineffective. In that case, avoidance or increasing the dose is a must.
- There are intermediate metabolizers, that are in-between the degrees of metabolism, some dose adjustment may be warranted.
Blood Brain Barrier (BBB)
This is a protein called the ‘p-glycoprotein pump’ (p-gp), it is encoded by a gene called the ABCB1. This pump acts as a barrier separating the blood and the brain and act to expel any substance recognized by the protein as foreign. Many anti-depressants are substrates (high affinity) of the ‘p-gp’ pump and are easily expelled from the brain, resulting in antidepressant failure. However,
- Some patients may have an ABCB1 variant that has a weakened (lower activity) P-gp protein, in that case, most antidepressants would work for them.
- Some antidepressants are not substrates of the BBB (not recognized by the P-gp protein), in that case these antidepressants would work for patients with the active variant of the ABCB1 gene.
- In some cases, the compatible medication might be a substrate of the BBB and the patient has the active variant of the ABCB1 gene. The psychopharmacist may recommend an increased dose or an inhibitor of the BBB as an adjunct medication.
Brain receptors (pharmacodynamics)
- This refers to the target transporters and receptors in the brain (i.e. SERT, HTR1A, DRD2, COMT and BDNF etc.) that the drug aims to block or excite.
- Depending on genetic expression, antagonism or inhibition of certain brain receptors, antidepressant occupancy may not be achieved effectively.
- For antidepressants to be compatible, the brain receptors of their mechanism of action must not have disagreeable variants.
They are specially trained pharmacists that have knowledge of both the mechanism of action of the antidepressants as well as the genes that are implicated in the outcomes of these antidepressants.
They navigate your genetic variants, interpret how these variants impact the many aspects of antidepressants and will produce a clear recommendation of the most compatible medication for you. They are available to you and your doctor to explain their recommendations.