How Pharmacogenetic Testing Can Support the Management of Neurological and Psychiatric Conditions

Mental health problems are among the leading causes of disease burden worldwide, encompassing a variety of nervous system disorders that still pose major challenges for medicine, both in diagnosis and treatment. 

 

To address these disorders, medication prescription is the main therapeutic strategy. However, treatment response can vary significantly from one patient to another due to genetic factors. This is where pharmacogenetic testing comes in, an innovative tool that makes it possible to personalize treatments according to each individual’s genetic profile. 

 

With pharmacogenetic testing, physicians can understand how genetic variants influence drug metabolism and effectiveness. This way, it becomes possible to recommend the most suitable medication, reduce side effects, and achieve better outcomes in the treatment of neurological and psychiatric conditions. 

 

Pharmacogenetic testing is already revolutionizing personalized medicine. Discover how this approach can transform clinical practice in the content we have prepared for you. 

What is Pharmacogenetics?

Pharmacogenetics is the field of medicine that studies how an individual’s genetic variations influence their response to medications. Combining pharmacology (the study of drugs) and genetics (the study of genes and inheritance), this field aims to develop personalized treatments that are more effective and have fewer adverse effects. 

 

These genetic variations can alter metabolizing enzymes, transporters, and receptors involved in the pathway a drug takes within the body. In other words, pharmacogenetics helps explain why some people metabolize a drug more quickly, while others do so more slowly, which can directly impact the effectiveness and safety of treatment. 

 

It is important to distinguish between pharmacogenetics and pharmacodynamics: 

• Pharmacogenetics: studies how a patient’s genes influence the absorption, metabolism, and elimination of medications;
• Pharmacodynamics: focuses on the effects of the drug on the body, that is, how the medication acts on its receptors and biological systems to produce the therapeutic effect.

Pharmacogenetics is particularly relevant in fields such as neurology and psychiatry, where treatments often involve a process of trial and error. Neurological and psychiatric disorders, such as epilepsy, depression, schizophrenia, and bipolar disorder, can be especially challenging to treat due to variability in patient response to medications. 

 

Major Neurological Conditions

Major depression (MD) is a highly prevalent neurological condition and one of the top global public health concerns. 

 

According to the World Health Organization (WHO), over 300 million people suffer from major depression, representing 4.4% of the global population (1). Additionally, a similar number face anxiety disorders, both incurring high healthcare costs and significantly impacting patients’ lives (2, 3). 

 

The complexity of depression, marked by variability in treatment response, presents a significant clinical management challenge. Responses to antidepressants vary widely among patients due to the interaction of genetic, environmental, and psychological factors. 

 

Although an increasing number of medications are available, psychiatry still relies on a “trial-and-error” model when selecting treatments, limiting success rates, especially for patients with mild depression (4, 5). Issues like poor treatment adherence and adverse effects further contribute to unsatisfactory outcomes. 

 

In some cases, depression becomes treatment-resistant, meaning it does not respond to at least two different classes of antidepressants administered at adequate doses for a sufficient period. This form of treatment-resistant depression accounts for 20% to 30% of MD cases (6), presenting an even greater challenge for professionals to find effective approaches for these patients. 

 

The Impact of Pharmacogenetics on the Treatment of Neurological and Psychiatric Diseases

The application of pharmacogenetics in the treatment of neurological and psychiatric disorders has the potential to revolutionize clinical practice. For example, in neurology, pharmacogenetics can help personalize treatments for conditions such as epilepsy, multiple sclerosis, and Parkinson’s disease.  

 

Patients with epilepsy may have genetic variants that affect the metabolism of anticonvulsants, and identifying these variants allows clinicians to adjust dosages to prevent seizures and minimize side effects. 

 

In psychiatry, pharmacogenetic analysis is particularly useful for disorders like depression, schizophrenia, and bipolar disorder. Many patients do not respond to the first prescribed medication, and pharmacogenetics can reduce the time needed to identify the right treatment. For example, genetic variants in the genes encoding drug-metabolizing enzymes can influence the efficacy of antidepressants and antipsychotics (7). 

 

Advances in pharmacogenomic studies have been highly relevant across various medical disciplines, especially in psychiatry. According to international guidelines, patients with complex conditions like bipolar disorder, major depressive disorder, psychotic depression, and borderline personality disorder should undergo these studies before initiating treatment due to the frequent use of combination therapies in these conditions (8). 

 

The Importance of Pharmacogenetics

Genetic variations can manifest at both pharmacokinetic and pharmacodynamic levels, ultimately resulting in distinct and personalized responses to specific treatments. 

 

Pharmacokinetic factors influence the plasma and tissue drug levels achieved with a given dose, determined by the processes of absorption, distribution, metabolism, and excretion. 

 

Pharmacodynamic factors govern the interaction between a drug and its receptor, leading to responses that may be more or less effective than expected. These factors affect receptors, enzymes, or proteins involved in signal transduction (9, 10). 

 

Moreover, the terms pharmacogenetics and pharmacogenomics are often used interchangeably. Pharmacogenetics refers to the study of individual genetic variability in genes associated with drug responses, while pharmacogenomics is used to describe the process of utilizing documented genetic variation to guide drug selection and dosing (11).

 

Pharmacogenetic studies aim to identify genetic variants and establish genetic biomarkers capable of influencing the magnitude of pharmacological effects, side effects, and drug interactions. These studies have become a cornerstone of personalized medicine, defining treatments based on each patient’s genetic profile (9, 12). 

 

However, therapeutic responses are influenced by various factors, including physiological aspects like age, sex, weight, and body fat; pathophysiological conditions like renal, hepatic, or cardiovascular function; environmental factors like smoking, alcohol consumption, nutrition, and pollutants; and genetic factors that affect the absorption, distribution, metabolism, and excretion of drugs. Personalized medicine involves tailoring patient treatment based on their genetic-molecular profile (12). 

 

Intestinal health and its connection with mental health

The gut microbiome plays a fundamental role in mental health, influencing disorders such as depression, anxiety, and ADHD. Changes in bacterial composition, known as dysbiosis, can affect mood through the so-called gut-brain axis, a bidirectional communication network that integrates the nervous, endocrine, and immune systems, connecting the gut and the brain (13). 

 

Intestinal microorganisms produce biologically active metabolites, such as short-chain fatty acids, GABA, and serotonin, which can reach the brain via the vagus nerve or the bloodstream, modulating neurotransmission, neural plasticity, and stress responses (14, 15). Alterations in this axis are also linked to activation of the HPA axis, systemic inflammation, and increased pro-inflammatory cytokines, factors often observed during depressive episodes (16). 

 

In addition, there is a feedback loop: depressive or anxious states can alter the microbiome, and these changes can, in turn, worsen psychiatric symptoms (17). This connection highlights how intestinal health is closely linked to mental well-being and suggests that strategies aimed at balancing the microbiome may have therapeutic potential. 

 

What is the purpose of pharmacogenetic testing in psychiatry? 

In clinical practice, one of the greatest challenges in psychiatry is that each person responds differently to medications. While some patients respond well from the beginning, others undergo several adjustments before finding the right medication and dose. 

 

It is precisely in this context that pharmacogenetic testing makes a difference. It helps understand how each individual’s genetic variations influence the way the body metabolizes and responds to drugs. In psychiatry, this is especially important in cases of depression, anxiety, and ADHD, where choosing the right medication can greatly accelerate clinical improvement. 

 

The test is usually recommended when the patient: 

• does not respond well to standard medications;
• experiences significant side effects;
• has a family history of difficulties with drug treatment;
• needs to start therapy with greater safety, avoiding a trial-and-error approach.

Pharmacogenetic testing does not replace medical evaluation, but it serves as a support tool, allowing treatment to be more targeted, safe, and effective from the start. 

 

What does pharmacogenetic testing reveal about medications?

The test analyzes variations in genes that influence how the body absorbs, distributes, metabolizes, and eliminates drugs (pharmacokinetics), as well as genes related to receptor sensitivity (pharmacodynamics). 

 

In practice, this makes it possible to identify, for example: whether a patient metabolizes an antidepressant slowly or rapidly; whether there is a higher risk of side effects; which drug classes are more likely to be effective. 

 

This information helps reduce the trial-and-error process, common in treatments for depression, anxiety, and other mental disorders. 

 

Pharmacogenetic testing does not replace medical evaluation and should not be used as a diagnostic tool—it does not indicate whether someone “has or does not have depression,” for example. Its role lies in therapeutic support, providing genetic information that guides the choice of the most appropriate drug and dose (7). 

 

Thus, it does not serve to confirm a diagnosis but can speed up treatment response and contribute to safer and more effective therapies. 

 

Key Genes in Psychiatric and Neurological Pharmacogenetics

 Several genes have been identified as important in psychiatric and neurological pharmacogenetics, including: 

• CYP2D6: This gene encodes a cytochrome P450 enzyme that metabolizes many psychiatric drugs, including antidepressants and antipsychotics. Variants in CYP2D6 can result in rapid or slow metabolizers, affecting drug efficacy and safety (18-21);
• CYP2C19: This gene is also involved in the metabolism of drugs such as antidepressants and anticonvulsants. Variants can influence treatment responses (22);
• HTR2A: This gene encodes a serotonin receptor targeted by many antidepressants. Variants in HTR2A can affect responses to selective serotonin reuptake inhibitors (SSRIs);
• COMT: The COMT gene encodes the enzyme catechol-O-methyltransferase, which degrades neurotransmitters like dopamine. Variants in COMT can influence responses to medications affecting dopamine levels, such as antipsychotics.

Variants in other enzymes involved in drug metabolism and transport also affect the pharmacokinetics and pharmacodynamics of drugs used in psychiatry and other medical fields.  

 

Benefits of Pharmacogenetic Analysis for Patients and Healthcare Professionals

The response to psychiatric medications varies greatly among individuals, both in therapeutic effects and the risk of adverse effects. Studies indicate that 60–70% of patients with depression do not achieve full remission with antidepressants, and 30–40% fail to respond adequately (23). 

 

Approximately 10% of patients discontinue antidepressants due to adverse effects. Antipsychotics and mood stabilizers are also frequently associated with side effects (24–26). 

 

It is estimated that up to 42% of variability in antidepressant response is attributable to common genetic variants (27). Hence, the establishment of pharmacogenetic biomarkers is crucial due to their implications for drug efficacy and associated side effects. 

 

Adverse drug effects are responsible for approximately 7% of hospitalizations, 20% of all readmissions, and about 4% of drug withdrawals from the market (28-30). 

 

In this context, pharmacogenetic analysis offers numerous benefits for both patients and healthcare professionals. 

 

For patients, key benefits include:

• Personalized Treatments: Tailoring treatments to individual genetic characteristics enhances drug efficacy and minimizes side effects;
• Reduced Treatment Time: By quickly identifying the most effective medications, pharmacogenetic analysis reduces the time needed to find the appropriate treatment, improving patients’ quality of life;
• Prevention of Adverse Reactions: Knowing genetic variants that influence drug metabolism helps avoid severe adverse reactions.

For healthcare professionals, benefits include: 

• Informed Decisions: Pharmacogenetic analysis provides valuable insights to guide treatment decisions, resulting in safer and more effective care;
• Treatment Efficiency: With accurate diagnoses and personalized treatments, healthcare providers can enhance care efficiency and reduce costs associated with ineffective therapies.

Understanding genetic variants involved in the expression of metabolizing enzymes enables the classification of a patient’s drug metabolism. 

 

The Future of Pharmacogenetics in Psychiatry and Neurology 

The future of pharmacogenetics in psychiatry and neurology is promising. As research progresses, pharmacogenetic analysis is expected to become a standard practice in medicine. Emerging technologies, such as next-generation sequencing (NGS), are making it easier and more affordable to identify relevant genetic variants. 

 

Additionally, integrating pharmacogenetics with other personalized medicine approaches, such as biomarker analysis and precision medicine, may lead to even more effective treatments. Collaboration among researchers, clinicians, and the pharmaceutical industry will be vital for the successful implementation of pharmacogenetics in clinical practice (7). 

 

Is pharmacogenetic testing worth it? 

Pharmacogenetic testing helps personalize psychiatric treatment by indicating which medications are more likely to be effective and carry a lower risk of side effects for each patient. 

 

Among the main advantages are: 

• Reduction of the trial-and-error process in medication selection;
• Greater safety and adherence to treatment;
• Optimization of dosages according to individual metabolism.

Limitations include the fact that the test does not replace clinical diagnosis, nor can it predict with 100% accuracy how a patient will respond to all medications, since environmental factors, lifestyle, and drug interactions also influence outcomes. 

 

Studies show that patients with depression, anxiety, or ADHD benefit from pharmacogenetic support, presenting better therapeutic responses and fewer adverse effects, while healthcare professionals report that testing supports clinical decision-making, making treatment more targeted, safe, and efficient (31). 

 

Which Pharmacogenetic Panel for Neurological Conditions Does SYNLAB Offer?

The Neuro PGx Pharmacogenetic Panel offered by SYNLAB evaluates variants in genes responsible for expressing key enzymes involved in the metabolism of medications commonly used to treat neurological and psychiatric conditions, such as depression, anxiety, schizophrenia, bipolar disorder, and others. 

 

The analysis provides relevant information on 81 medications widely used in clinical practice, based on the study of 50 genetic variants documented in scientific literature and found in 8 genes: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, CYP2B6 and ABCB1. 

 

To standardize and facilitate the implementation of pharmacogenetics in clinical practice, international expert consortia, such as the Clinical Pharmacogenetics Implementation Consortium (CPIC), Pharmacogene Variation Consortium (PharmVar), American College of Medical Genetics and Genomics (ACMG), American College of Molecular Pathology (ACMP), and the Human Genome Variation Society (HGVS), among others, are dedicated to issuing and updating evidence-based clinical guidelines. These include drug-gene associations, evidence levels, standardized terminology, and clinical recommendations (32-37). 

 

Currently, over 35 guidelines are available on the Pharmacogenomics Knowledge Base (PharmGKB) website (38). Various platforms store comprehensive information in their databases to guide clinicians in practice, and SYNLAB adheres to all these guidelines in the development of its pharmacogenetic panels. 

 

Which medications are analyzed in the Neuro PGx Pharmacogenetic Panel?

The panel analyzes 81 medications from the following classes: 

• CENTRAL ACTING ADRENERGIC AGONISTS: Clonidine, Guanfacine;
• ANTIDEPRESSANTS: NMDA RECEPTOR BLOCKERS: Ketamine, Esketamine;
• ANTIDEPRESSANTS: SEROTONIN RECEPTOR ANTAGONIST AND REUPTAKE INHIBITORS (SARI): Trazodone;
• ANTIDEPRESSANTS: SELECTIVE NOREPINEPHRINE REUPTAKE INHIBITORS: Levomilnacipran, Reboxetine;
• ANTIDEPRESSANTS: MONOAMINE OXIDASE A INHIBITORS: Moclobemide;
• ANTIDEPRESSANTS: NOREPINEPHRINE AND DOPAMINE REUPTAKE INHIBITORS (NDRI): Bupropion;
• ANTIDEPRESSANTS: SELECTIVE NA AND 5HT REUPTAKE INHIBITORS: Duloxetine, Venlafaxine;
• ANTIDEPRESSANTS: SELECTIVE SEROTONIN REUPTAKE INHIBITORS: Citalopram, Escitalopram, Fluvoxamine, Paroxetine;
• ANTIDEPRESSANTS: SELECTIVE SEROTONIN REUPTAKE INHIBITORS: Sertraline;
• OTHER ANTIDEPRESSANTS: Agomelatine, Maprotiline, Mianserin, Mirtazapine, Vilazodone, Vortioxetine;
• ANTIDEPRESSANTS: TRICYCLIC ANTIDEPRESSANTS: Amitriptyline, Clomipramine, Desipramine, Dothiepin, Doxepin, Imipramine, Nortriptyline, Trimipramine;
• ANXIOLYTICS: Alprazolam, Bromazepam, Buspirone, Clobazam, Clonazepam, Chlordiazepoxide, Diazepam, Flurazepam, Ketazolam, Triazolam;
• ANTIEPILEPTICS: Phenobarbital;
• ANTIPSYCHOTICS: Amisulpride, Aripiprazole, Asenapine, Brexpiprazole, Bromperidol, Cariprazine, Clozapine, Droperidol, Fluphenazine, Flupentixol, Haloperidol, Iloperidone, Levomepromazine, Loxapine, Lurasidone, Olanzapine, Perphenazine, Pimavanserin, Pimozide, Pipotiazine, Quetiapine, Risperidone, Sertindole, Thioridazine, Trifluoperazine, Zuclopentixol;
• HYPNOTICS AND SEDATIVES: Amobarbital, Brotizolam, Eszopiclone, Hydroxyzine, Mephobarbital, Zaleplon, Zolpidem, Zopiclone;
• PARKINSON AND ALZHEIMER’S: Levodopa, Rasagiline, Selegiline;
• ADHD: AMPHETAMINES: Atomoxetine, Caffeine, Dexamfetamine, Lisdexamfetamine.

 

Who is the Neuro PGx test intended for?

The SYNLAB Neuro PGx Pharmacogenetic Panel is intended for: 

• Patients with neurological or psychiatric conditions, such as depressive, psychotic, anxiolytic, or hypnotic disorders, who wish to personalize their treatment based on their genetic profile;
• Patients undergoing pharmacological treatment who do not achieve expected outcomes, with persistent symptoms despite medication;
• Patients on polypharmacy regimens;
• Patients experiencing significant side effects from medications.

 

What is the methodology used for the test?

The SYNLAB Neuro PGx Pharmacogenetic Panel utilizes the MassARRAY platform, which employs mass spectrometry to rapidly and accurately identify genetic variations, such as single nucleotide variants (SNVs), insertions, deletions, and mutations. 

 

The MassARRAY methodology combines DNA amplification with mass spectrometry detection. Initially, DNA is amplified via PCR. Instead of directly detecting the PCR products, the amplified fragments undergo allele-specific extension reactions. Subsequently, these fragments are ionized and analyzed by mass spectrometry, enabling the determination of the molecular weight of each genetic variant. 

 

Why perform the Neuro PGx panel?

Human genome variation is a key factor in modulating individual responses to medications. Pharmacogenetics studies how genetic differences influence drug responses.

 

The metabolism of a drug involves various reactions that generally modify it into a more soluble molecule for easier excretion.  

 

Several genes encoding enzymes involved in drug metabolism pathways contain genetic variants that alter enzyme expression, selectivity, or activity, leading to diverse drug responses. Thus, assessing the genetic profile based on these variants has become crucial for understanding drug metabolism. 

 

What other pharmacogenetic tests does SYNLAB offer?

SYNLAB also offers the following pharmacogenetic test: Global PGx.

 

This analysis provides relevant information about 161 drugs widely used in clinical practice, by examining 55 genetic variants present in the following genes: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A5, ABCB1, COMT, FACTOR II, FACTOR V, MTHFR, SLCO1B1 and VKORC1. 

 

 

Frequently Asked Questions about Pharmacogenetic Testing (FAQ)  

In this section, we answer the main questions about pharmacogenetic testing and its applications. 

 

Does pharmacogenetic testing detect depression?

No. Pharmacogenetic testing is not designed to diagnose depression or other psychiatric disorders. The diagnosis of depression remains clinical. The test’s role is to help select the most appropriate medication for each patient, considering their genetic profile. 

 

What is the best pharmacogenetic test?

The best test is the one that evaluates relevant genes for the metabolism of medications used in psychiatric treatment, with validated methodology and reliable clinical interpretation. 

 

How should pharmacogenetic test results be interpreted?

The results indicate how a patient metabolizes different medications and which drugs are more or less likely to be effective or cause side effects. Interpretation should always be done by a healthcare professional, who will integrate this information into the patient’s clinical history and individualized treatment plan. 

 

Which test can detect depression?

There is no test that directly detects depression. The diagnosis is clinical, based on medical evaluation, patient history, and, in some cases, the use of specific assessment scales performed by a mental health professional. 

 

How is pharmacogenetics applied in psychiatry?

The test helps select medications and dosages that are more compatible with the patient’s genetic profile, reducing side effects and increasing treatment effectiveness. 

 

What is the relationship between the gut and mental health?

The gut and the brain communicate through the gut-brain axis, involving the nervous, endocrine, and immune systems. A balanced microbiome influences neurotransmitter production, regulates stress responses, and may impact conditions such as depression and anxiety. 

 

How can I know if my gut is healthy?

Signs of gut balance include good digestive function, regular bowel movements, absence of chronic discomfort, and overall well-being. Specific tests, such as gut microbiota analysis, can provide detailed information about the composition and functioning of the intestine. 

 

Discover SYNLAB, a reference in the provision of medical diagnostic services!  

Conducting precise and up-to-date tests is essential for more accurate diagnoses and better treatment planning. SYNLAB is here to support you. 

 

We offer diagnostic solutions with rigorous quality control to the companies, patients, and physicians we serve. Present in Brazil for over 10 years, we operate in 36 countries across three continents and are leaders in service provision in Europe. 

 

Contact the SYNLAB team to learn more about the available tests. 

 

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