How Genetics Influence SSRI Effectiveness

What Are SSRIs & How Do They Work?

SSRIs, or Selective Serotonin Reuptake Inhibitors, are a class of medications that cause
serotonin naturally found in your nervous system to concentrate in the space between the nerves, which ultimately transmits adaptations throughout the nervous system (including the brain). They do this by blocking a transporter that re-absorbs serotonin into the sending neuron (to be subsequently broken down) from the space where it interacts with the receiving neuron. Over time, this is what contributes to SSRI effectiveness, which includes reducing symptoms of depression (like low mood and loss of interest in most activities) and/or anxiety (like persistent worry), but also contributes to SSRI side effects.

Why SSRIs Work Differently for Each Person

SSRI efficacy and side effects are influenced by several factors. This can include the
specifics of your diagnosis, the health and functioning of your liver and kidneys, interactions with other medications you might be taking, your medical history, pregnancy and genetic factors. In fact, genetic differences can result in an increased risk of side effects, or, in other cases, reduced likelihood of benefit when they are prescribed based on generally accepted dosing ranges.

What Pharmacogenetics Reveals About SSRI Response

SSRI genetic testing identifies genetic variations in key genes responsible for metabolizing these medications. These variations can result in reduced functioning of these enzymes, which can result in accumulation of these medications as they aren't being cleared from your body as we would hope. This accumulation means the medications are "over-staying their welcome" when it's time for the next dose to be taken. As a result, side effects become more likely, or are worse than would otherwise be seen. On the other hand, for many SSRIs, the opposite can happen. Due to other genetic variants that cause over-functioning of these metabolizing enzymes, the SSRI is cleared too rapidly from the body. This means that they don't have enough time to exert their effects and help control mental health symptoms as would be expected. By using knowledge of this information, prescriber decisions to use the medication (per usual or with modified dosing) or consider alternatives can be enhanced. [1]

Escitalopram vs Sertraline: What Genes Can Tell Us

Both escitalopram and sertraline are significantly metabolized by the enzyme for the gene CYP2C19. However, other enzymes can also play roles in metabolizing each of these medications. In fact, in the case of sertraline, the role of CYP2B6 can also significantly impact its overall metabolism, which helps differentiate its metabolism from that of escitalopram. As a result, it is important to look at the combination of variations (or lack thereof) in both CYP2C19 and CYP2B6. In fact, in many cases, variations in each respective gene can offset one another, resulting in a normal or expected response to sertraline. In others, they may only partially offset one another, or be additive (e.g., reduced or increased function in both genes and thus potentially creating relative sertraline contraindications). As a result, insights into modified dosing or even whether to use at all can be considered because of genetically informed knowledge of sertraline side effects and sertraline effectiveness. [1]

In the case of escitalopram, only the impact of variations in the CYP2C19 gene are known to have such an impact that the way it is prescribed could be adjusted, if at all. This means that variations in CYP2C19 can result in slower or faster metabolism, an increased risk of escitalopram side effects or reduced chances of experiencing benefit.

When to Consider Genetic Testing for Your SSRI

Pharmacogenetic testing may be helpful if you are at the early stages of treatment with an SSRI, helping inform your health care provider's choices from the start. It can also be
helpful if you have previously found that SSRIs medications did not work well and/or caused difficult side effects.

How Inagene Supports Personalized SSRI Treatment

Pharmacogenetic testing provides actionable insights that can support health care providers in their medication treatment decisions. The results help identify which medications or dosing strategies are more compatible with a person’s genetic profile, helping to improve symptom management and reduce side effects. Practically speaking, this may mean that some individuals may have specific dosing requirements (higher or lower than usual) or a modified frequency of dose adjustments. It could also mean that other treatment options for depression or anxiety should be explored instead. These insights can help health care professionals better tailor their approach to the individual being treated.

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