Introduction

Depression is a common mental health disorder that affects millions of people worldwide. It can cause feelings of sadness, loss of interest in activities, and a variety of physical and emotional symptoms. While there are several treatment options available, including therapy and medication, finding the right antidepressant medication can be a challenging and often frustrating process. Trial-and-error in medication selection can lead to prolonged suffering and can even be life-threatening. However, recent advancements in genetics have led to the development of a DNA test that can help determine which antidepressant medication may work best for an individual.

The DNA test, known as a pharmacogenomic test, analyzes an individual's genetic makeup to determine how their body metabolizes medication. This test can identify genetic variations that can impact how the body processes and responds to different antidepressant medications. This information can then be used by a healthcare provider to tailor treatment plans to the individual's specific genetic makeup, increasing the likelihood of finding an effective and safe medication.

In this article, we will explore the DNA test for antidepressants and how it can help individuals suffering from depression find the right medication for their unique needs.

What is a Pharmacogenomic Test?

Explanation of How a Pharmacogenomic Test Works

Pharmacogenomic (or pharmacogenetic) testing is a medical test that analyzes an individual's genetic makeup to predict their response to certain medications. This testing combines the fields of pharmacology (the study of how drugs work in the body) and genetics (the study of genes and their impact on traits and diseases). The sample collected is processed and then analyzed. The results are then compared to known genetic variants that have been shown to influence how a person metabolizes or responds to certain medicines.

Advantages of Using a Pharmacogenomic Test for Antidepressants

  • Personalized treatment: Antidepressants, as well as many other medicines, work differently in different people. Pharmacogenetic testing (PGX), as part of precision medicine, helps to tailor your therapy, reducing the need for trying multiple medications before finding one that helps to reduce your depression symptoms.
  • Increased safety: Antidepressants may lead to adverse drug reactions. PGX testing can help eliminate the medications most likely to cause an issue.
  • Reduced cost: The trial-and-error process historically used can result in the need to try multiple different medications, multiple dose adjustments, and more frequent visits. PGX testing saves both time and money. Patients suffering from severe depression or bipolar commonly try multiple medications before finding complete symptom relief.

Types of Genetic Variations That Can Impact Medication Metabolism

  • Single Nucleotide Polymorphisms (SNPs): The most common change in our genes is one small change in a single nucleotide base of the DNA sequence. (Nucleotides are the building blocks that make up our DNA.) This is like changing the spelling of a word by one letter causing the upcoming word to have a different meaning or is not a word at all.
  • Insertions and deletions: Similar to SNPs but with a nucleotide being added or removed. This is when DNA ‘words’ are changed by adding or deleting ‘letters’. Often these genes become non-functional.
  • Copy Number Variations (CNVs): Some genes are more likely to be duplicated than others. The duplication may lead to the production of extra copies of certain enzymes.  CNVs can change gene dosage and affect protein activity. This can alter drug metabolism or response for enzymes and targets. Some of these genes can end up having multiple copies, the larger the copy number the greater the impact.
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How the Test Works for Antidepressants

Explanation of how the DNA Test for Antidepressants Works

A DNA test for antidepressants analyzes an individual's genetic makeup to determine how they may respond to multiple psychological medications. Genetic variations related to drug metabolism and response are identified to guide treatment decisions and personalize medication choices. Your depression disorder, along with your medical history and blood tests results, guides the type of treatment chosen. Precision medicine takes your entire history into account. Pharmacogenetic testing serves an integral part.

Sample Collection Process

There are a variety of ways to collect a sample. DNA can be found in most body samples; however, a pharmacogenomic test is usually taken one of three ways.

  • Blood sample: A healthcare professional collects a small blood sample with a needle and syringe. The blood is then processed in a laboratory to isolate the DNA.
  • Cheek swab (Buccal Swab): A sterile swab is rubbed against the inside of your cheek to collect cells containing DNA. The swab is then placed in a container and sent to a lab to extract the DNA.
  • Saliva sample: You provide a sample of your saliva by spitting into a collection tube provided. The tube is then sealed and sent to a laboratory where the DNA is extracted.

Laboratory Analysis of DNA Sample

The DNA is isolated from the sample using the method of extraction most appropriate to the type of sample collected. When the DNA is isolated, it is then replicated through a process called PCR. PCR, or polymerase chain reaction, is used to amplify a specific segment of DNA through a series of heating and cooling cycles allowing the DNA to be copied exponentially. The result is millions of copies of the targeted sequence. These copies are then sequenced to determine the precise order of nucleotides in the DNA. The results are then checked for known genetic variations that are associated with drug response.

Using Test Results to Choose Antidepressants

Explanation of How Healthcare Providers Use the Test Results to Choose Medications

Healthcare providers use test results to choose antidepressant medications by considering the patient's genetic profile to select more effective and well-tolerated options, adjust dosage if needed, avoid risky medications, and minimize trial-and-error in treatment selection.

Tailor Treatment Plans to an Individual’s Genetic Makeup

  1. Medications selection: There are dozens of antidepressants. Test results can be used by your primary care provider or psychiatrist to reduce the number of potential candidates.
  2. Dosage optimization: Genetic variations can affect how you metabolize a medicine. The test results may suggest that a smaller or larger dose is preferred.
  3. Avoid Risky Medications: The test results help identify medications that have a higher risk of adverse drug reactions or poor response to specific antidepressants. There may be instances when the only appropriate medicine available is more likely to cause common side effects; knowing ahead of time will help your prescriber better treat any symptoms that appear.
  4. Minimize trial-and-error: When we find the right antidepressant medication at the beginning, it helps us save time and money, makes it easier to stick to the treatment, and increases the chances of positive results. Those with treatment resistant depression may finally find relief by having a genetic drug test.
  5. Personalized treatment approach: Precision medicine increases positive outcomes and patient satisfaction. Personalized healthcare empowers patients and doctors by increasing patient satisfaction and engagement.

Examples of How the Test Results can Impact Medication Selection

  1. Selective Serotonin Reuptake Inhibitors (SSRIs): Medications in this class, such as fluoxetine and escitalopram, are commonly prescribed for depression. The enzymes CYP2C19 and CYP2D6 can affect the metabolism of SSRIs. Differences in these genes can affect how quickly or slowly your body processes these medications resulting in medications being less effective or having increased side effects.
  2. Tricyclic Antidepressants (TCAs): This is an older class of antidepressants still prescribed when other medications have failed. Tricyclic antidepressants, such as amitriptyline and nortriptyline, have a higher risk of side effects and of overdose than the newer antidepressant classes. TCAs are affected by genetic variations in the CYP2D6 enzyme which may lead to poorer effectiveness and increased side effects.
  3. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): SNRIs, such as venlafaxine and duloxetine, are another class of antidepressants. Similar to SSRIs, variations in the CYP2D6 enzyme can influence their metabolism leading to potentially ineffective response or greater adverse events.
  4. Monoamine Oxidase Inhibitors (MAOIs): MAOIs, such as phenelzine and tranylcypromine, are less commonly prescribed due to many interactions with foods and medications. Interactions in the gene responsible for encoding the enzyme monoamine oxidase (MAOA) can influence an individual's response to MAOIs; leading to potentially poor efficacy and adverse reactions.
  5. Atypical antidepressants: Bupropion, affected by variants in the CYP2D6 gene, primarily inhibits the reuptake of dopamine and norepinephrine. Vilazodone, affected by CYP2C19, CYP2D6 and others, modulates serotonin levels differently than SSRIs. Variants in these genes could alter effectiveness or lead to adverse drug reactions.

Conclusion

Knowing your pharmacogenomic profile will help you and your healthcare provider determine which medications may work best in your body with the least risk of side effects. Thankfully, many people can discover a regimen that works well for them even after having tried multiple other medications. Doing this test prior to needing therapy would help prevent much of the trial-and-error commonly seen in depression treatments.

Looking for help determining the best medication options for your specific health concern? See how ClarityX can help!

Resources

  1. https://medlineplus.gov/lab-tests/pharmacogenetic-tests/
  2. https://www.psychiatrist.com/pcc/neurologic/neurology/pharmacogenetic-guided-treatment-for-neuropsychiatric-disorders/
  3. https://www.pharmgkb.org/whatIsPharmacogenomics
  4. https://www.yourgenome.org/facts/what-is-pharmacogenomics/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682947/
  6. fluoxetine: Dosing, contraindications, side effects, and pill pictures - epocrates online
  7. escitalopram: Dosing, contraindications, side effects, and pill pictures - epocrates online
  8. amitriptyline: Dosing, contraindications, side effects, and pill pictures - epocrates online
  9. nortriptyline: Dosing, contraindications, side effects, and pill pictures - epocrates online
  10. phenelzine: Dosing, contraindications, side effects, and pill pictures - epocrates online
  11. tranylcypromine: Dosing, contraindications, side effects, and pill pictures - epocrates online
  12. bupropion hydrochloride: Dosing, contraindications, side effects, and pill pictures - epocrates online
  13. vilazodone: Dosing, contraindications, side effects, and pill pictures - epocrates online