What Are Liver Enzymes?

Liver enzymes are genes process a medication after you take it.

They can influence how quickly a medicine is:

1. absorbed
2. processed by the liver
3. carried through the body
4. broken down
5. removed from the body

For mental health medications, the most important effect is often how quickly the liver breaks the medication down. These are also known as pharmacokinetic genes that help determine what your body does with a medication after you take it.

Why Does This Matter?

Two people can take the same medication at the same dose but have very different amounts of that medication in their body.

One person may break it down quickly.

Another may break it down slowly.

This can affect whether the medication:

• Works well
• Does not work well enough
• Causes side effects
• Builds up to a higher level than expected Your genes are one reason these differences can occur.

Think of Liver Enzymes as Medication Workers

The liver contains enzymes that help process medications.

You can think of these enzymes as workers in a medication-processing factory.

Your genes provide the instructions for how well those workers function.

Depending on your genetics, some workers may be:

• Slow

1. The medication is removed more slowly.
2. More medication may remain in the body.
3. Side effects may be more likely for some drugs.

• Normal

1. The medication is processed at the expected rate.
2. Standard doses may work as expected.

• Fast

1. The medication may be removed more quickly.
2. Less medication may remain in the body.
3. The medication may not work as well for some drugs.

The effect is different for every medication, so being a fast or slow metabolizer is not automatically good or bad.

Important Pharmacokinetic Genes in Mental Health Medications

Several genes are particularly important because they help process many psychiatric medications.

• CYP2D6 CYP2D6 helps process many:

• Antidepressants

• Antipsychotics

• ADHD medications Examples include medications such as, paroxetine, venlafaxine, vortioxetine, aripiprazole, brexpiprazole, risperidone and atomoxetine.

If CYP2D6 works very slowly, some medications may build up.

If it works very quickly, certain medications may be cleared faster.

• CYP2C19 CYP2C19 is important for several antidepressants, including citalopram, escitalopram and sertraline.

A person who processes these medications slowly may have higher medication levels.

A person who processes them very quickly may have lower levels.

This information can sometimes help a clinician decide whether to adjust the dose or consider another medication.

• CYP1A2 CYP1A2 helps process medications such as clozapine and olanzapine**.**

Genetics can influence this enzyme, but so can other factors.

For example, cigarette smoke can make CYP1A2 work faster, while some medications can slow it down.

This is a good example of why genes are only one part of medication response.

• CYP2B6 CYP2B6 helps process some mental health medications, including bupropion and sertraline**.**

Genetic differences can change how active this enzyme is and therefore influence medication exposure.

CYP3A4 and CYP3A5

These enzymes process many medications.

However, their activity is often strongly affected by:

• Other medications
• Foods
• Supplements
• Medical conditions For many psychiatric medications, these factors may be more important than genetic differences alone.

What Do “Poor” and “Rapid Metabolizer” Mean?

A pharmacogenomic report may describe someone as:

• Poor Metabolizer The enzyme works very slowly or hardly at all.

For some medications:

1. Drug breaks down slowly
2. Higher medication exposure
3. Greater chance of side effects

• Intermediate Metabolizer The enzyme works, but more slowly than usual.

• Normal Metabolizer The enzyme works at the expected rate.

• Rapid Metabolizer The enzyme works faster than usual.

• Ultrarapid Metabolizer The enzyme works much faster than usual.

For some medications:

1. Drug is removed quickly
2. Lower medication exposure
3. Medication may be less effective

But these effects are drug specific. Some medications are converted into their active form by an enzyme, so the effect can sometimes be the opposite.

How Pharmacokinetic Genes Can Help with Mental Health Medications

Pharmacokinetic information may help answer questions such as:

• Is this person likely to process this medication normally?
• Could the medication build up and cause side effects?
• Could the medication be removed too quickly to work properly?
• Would another medication be easier for this person’s body to process?
• Should the clinician consider a different starting dose? This can provide useful information before or during treatment.

A Simple Example

Imagine two people both take the same antidepressant.

Person A

Breaks the medication down normally.

1. Standard dose
2. Expected medication level
3. Good chance of normal exposure

Person B

Breaks the medication down very slowly.

1. Same dose
2. Medication remains in the body longer
3. Higher medication level
4. Greater possibility of side effects

The medication is the same.

The dose is the same.

But their bodies handle it differently.

Pharmacokinetics Does Not Tell the Whole Story

Knowing how a person processes a medication is important, but it does not tell us everything about whether the medication will work.

A useful distinction is:

Pharmacokinetics: What your body does to the medication

Pharmacodynamics: What the medication does to your brain and body

A person can process a medication perfectly normally but still not respond well to it.

That is why medication selection should consider:

• Pharmacokinetic genetics
• How the medication works
• Symptoms
• Previous medication response
• Other medications and medical conditions More personalized prescribing

Simple Summary

Pharmacokinetic genes influence how your body processes medications. Some people break certain mental health medications down slowly, while others process them very quickly. This can affect how much medication reaches the body, how well it works and the chance of side effects. Pharmacogenomic testing can help clinicians understand these differences and, when appropriate, choose a medication or dose that better fits the individual.