Is Anxiety Inherited?

Genetic Testing For Anxiety

by Melissa Smith, PharmD, CPH

In this day and age, it is inevitable for people to experience anxiety on occasion. However, there are individuals that deal with debilitating symptoms from diagnosed anxiety disorders. Anxiety disorders can make it very difficult to function normally; paralyzed by the fear of the unknown. One’s life can be so profoundly impacted it can affect the daily grind of existence in things such as job performance, social relationships, and schoolwork. [1]

According to the Morbidity and Mortality Weekly Report (MMWR) from the Center on Disease Control and Prevention (CDC) the percentage of adults with more recent symptoms of anxiety and depressive disorders rose from 36.4% to 41.5% from August 2020 to February of 2021.[2] With growing concern in mental health in society, it is imperative that mental health care teams have access to the most up to date diagnostic tools to help their patients. Pharmacogenomics (PGx) testing is an evidence based genetic test that can help providers find the most appropriate therapy for their patients. ClarityX has a specialized PGx test called the Mindwell test that provides insights specifically to mental health medications unique to their patient’s individual genetic profile.

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Anxiety Disorders

It is completely normal for people to experience anxiety and can be beneficial in some scenarios. Anxiety is referred to as the anticipation of future concerns that can present with symptoms of muscle tension and avoidance behaviors. Anxiety has been shown to affect nearly 30% of adults in their lifetime. However, anxiety disorders significantly differ from more common feelings of anxiety. There are a wide variety of anxiety disorders some examples include: Generalized Anxiety Disorder, Social Anxiety Disorder, Separation Anxiety Disorder, and Phobias (ex. Agoraphobia).[3] The good news is that anxiety disorders can be managed by the patient and mental health providers with counseling and prescription medications. However, prescription medications can be difficult to pinpoint for each patient and they can take up to 4-6 weeks to start providing relief of anxiety symptoms. The Mindwell test from ClarityX is an excellent tool that can be utilized to reduce the trial-and-error method of prescribing medications, potentially expediting the relief of symptoms of anxiety.

Treatments for Anxiety Disorders

There three areas that are usually covered when treating individuals diagnosed with anxiety disorders. Typically, patients are initially treated with psychological counseling which can include methods such as cognitive behavioral therapy, and behavior techniques. However, prescription medications are the first line of defense for mental health providers to implement when getting the symptoms of anxiety under control for their patients. If patients are not able to control the symptoms of anxiety with medications the likelihood of successful treatment of the anxiety disorder becomes exponentially more difficult.[4]

The key players when first prescribing medications for anxiety disorders fall into the following classes of medications: Serotonin Reuptake Inhibitors (SSRI’s), Serotonin Norepinephrine Reuptake Inhibitors (SNRI’s), Tricyclic Antidepressants (TCA’s), and Benzodiazepines. Some examples of commonly utilized medications by providers are citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), venlafaxine (Effexor), duloxetine (Cymbalta), and alprazolam (Xanax). All these medications have pharmacogenomic supporting evidence that can help providers in deciding which therapies would be most appropriate for their patients based on their genetics.[5]

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Pharmacogenetic (PGx) Testing Overview

To comprehend pharmacogenomics there needs to be a basic knowledge of how DNA can impact the genes that influence drug metabolism. It is easiest to think of DNA as a code that utilizes the letters A, C, G, and T to comprise its many genes. Different combinations of these letters signify the instructions those genes utilized to produce proteins in the body. Proteins are made up of amino acids sequenced from a corresponding gene. Proteins carry out many different functions of the body and one of those functions the breakdown of medications (CYP450 enzymes). The presence of genetic variations in the genes can impact the instructions needed to produce these enzymes, affecting how individuals respond to medications. [6]

There are typically five ways to identify genetic variations in these enzymes in PGx testing they are as follows: Poor Metabolizer, Intermediate Metabolizer, Normal Metabolizer, Rapid Metabolizer, and Ultra-Rapid Metabolizer. These labels foreshadow how medications can be broken down in the body or activated. Low enzymatic activity may prevent a patient from metabolizing medications like antidepressants and antipsychotics. When the drugs remain in the system too long, they can cause serious side effects. In contrast, in those with high levels of enzymatic activity, medications can break down too quickly resulting in no therapeutic benefit.

According to the Clinical Pharmacogenetics Implementation Consortium (CPIC) there is meaningful, well documented evidence to support the findings around the enzymes CYP3A4 and CYP2C19 being affected by genetic variations. The genetic variations of these enzymes have been clinically shown to alter the effects of serotonin reuptake inhibitors (SSRIs) and benzodiazepines, which are common first-line therapies prescribed when treating anxiety disorders. Patients potentially could experience treatment failure if these genetic variations are not identified prior to initial treatments. In addition, nearly 25,000 patients annually in the United States will need to go to the emergency department due to adverse events caused by antidepressants.[7]

SSRIs Affected by Genetic Variations in CYP2C19

Three common SSRI treatments in mental health are citalopram (Celexa), and escitalopram (Lexapro). These medications can be strongly affected by patients that carry the genetic variant to make the enzyme CYP2C19 have ultrarapid metabolism. Having CYP2C19 ultrarapid metabolism with these medications can cause a person to not have any therapeutic benefit because the drugs are eliminated out of the body too quickly. Conversely, if a patient is found to be a poor metabolizer of CYP2C19, the patient may experience a buildup of the medication in the body and experience side effects or adverse events.[8]

Benzodiazepines Affected by Genetic Variations in CYP3A4

A common benzodiazepine that is regularly prescribed when treating anxiety disorders is alprazolam (Xanax). Alprazolam is strongly affected by the metabolism of the CYP3A4 enzyme. It can be affected in two ways. If a patient is found to carry two copies of CYP3A4*1 allele, there is a lower likelihood of this patient experiencing adverse events. Conversely, if a patient has one copy of CYP3A4*22 allele in combination with one copy of *1 allele this patient may have an increased risk of side effects or adverse events that could result in hospitalization.[9]

Mindwell Test Benefits

There are so many antidepressant and psychiatric medication options for patients dealing with anxiety disorders. It can be overwhelming for all involved to find the right treatment plan. Choosing the wrong medication can produce a number of unpleasant side effects and sometimes the original problem remains unresolved. Luckily having access to this invaluable pharmacogenomic information is just a click away. The Mindwell test from ClarityX provides a seamless in-home testing experience for its customers. Simply visit the website clarityxdna.com, select the Mindwell test option from the drop-down menu and complete the checkout process. Once the kit is received follow the package instructions, activate your kit, perform a simple cheek swab, and then mail the sample back using the prepaid envelope. The sample is then sent to the lab for processing and the results are received by the customer and provider in 7-14 days on average. One of the most important facts about pharmacogenetic (PGx) testing is the results can be reevaluated for future medication changes as this test does not have to be repeated for those specific genes tested. Another key function of the Mindwell test is specific medications can be entered to be evaluated to see how an individual’s genetic make-up can affect those therapies. Speak to your provider today about implementing information from the Mindwell test in your treatment plan.

Citations

[1] U.S. Department of Health and Human Services. (n.d.). Anxiety disorders. National Institute of Mental Health. Retrieved May 9, 2022, from https://www.nimh.nih.gov/health/topics/anxiety-disorders

[2] Centers for Disease Control and Prevention. (2021, April 1). Symptoms of anxiety or depressive disorder and use of mental health care among adults during the COVID-19 pandemic – United States, August 2020–February 2021. Centers for Disease Control and Prevention. Retrieved May 9, 2022, from https://www.cdc.gov/mmwr/volumes/70/wr/mm7013e2.htm

[3] What are anxiety disorders? Psychiatry.org – What are Anxiety Disorders? (n.d.). Retrieved May 9, 2022, from https://psychiatry.org/patients-families/anxiety-disorders/what-are-anxiety-disorders

[4] Gautam, S., Jain, A., Gautam, M., Vahia, V. N., & Gautam, A. (2017, January). Clinical practice guidelines for the management of Generalised Anxiety Disorder (GAD) and panic disorder (PD). Indian journal of psychiatry. Retrieved May 9, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310105/

[5] Anxiety Disorders. PharmGKB. (n.d.). Retrieved May 9, 2022, from https://www.pharmgkb.org/disease/PA447196/clinicalAnnotation

[6] https://www.pharmgkb.org/whatIsPharmacogenomics

[7] Hicks, J. K., Bishop, J. R., Sangkuhl, K., Müller, D. J., Ji, Y., Leckband, S. G., Leeder, J. S., Graham, R. L., Chiulli, D. L., LLerena, A., Skaar, T. C., Scott, S. A., Stingl, J. C., Klein, T. E., Caudle, K. E., & Gaedigk, A. (2015). Clinical pharmacogenetics implementation consortium (CPIC) guideline forcyp2d6andcyp2c19genotypes and dosing of selective serotonin reuptake inhibitors. Clinical Pharmacology & Therapeutics, 98(2), 127–134. https://doi.org/10.1002/cpt.147

[8] Hicks, J. K., Bishop, J. R., Sangkuhl, K., Müller, D. J., Ji, Y., Leckband, S. G., Leeder, J. S., Graham, R. L., Chiulli, D. L., LLerena, A., Skaar, T. C., Scott, S. A., Stingl, J. C., Klein, T. E., Caudle, K. E., & Gaedigk, A. (2015). Clinical pharmacogenetics implementation consortium (CPIC) guideline forcyp2d6andcyp2c19genotypes and dosing of selective serotonin reuptake inhibitors. Clinical Pharmacology & Therapeutics, 98(2), 127–134. https://doi.org/10.1002/cpt.147

[9] Clinical Annotation for CYP3A4*1, CYP3A4*22; alprazolam; adverse events, Alcoholism and Anxiety Disorders (level 3 Toxicity). PharmGKB. (n.d.). Retrieved May 9, 2022, from https://www.pharmgkb.org/clinicalAnnotation/1451725560

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