Pharmacogenomics-informed Pharmacotherapy for Psychiatric Disorders

(PSY-PGx Trial)

Recruiting at 8 trial locations

Overseen By Roos van Westrhenen, Ass. Prof.

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Maastricht University Medical Center

Must be taking: Sertraline, Escitalopram, Aripiprazole, Risperidone

Disqualifiers: Severe somatic comorbidities, Alcohol/substance abuse, Polypharmacy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

2500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if personalized medication advice based on genetic testing can help people with mood, anxiety, or psychotic disorders more effectively than standard dosing. Participants will receive either medication tailored to their genetic makeup or the usual dosing without genetic information. The trial seeks individuals who have struggled to respond to current psychiatric medications and are switching to specific medications like sertraline or aripiprazole. Participants should already be receiving psychiatric treatment and possess a smartphone for monitoring. As an unphased study, this trial offers a unique opportunity to explore personalized treatment options that could enhance medication response.

Do I have to stop taking my current medications to join the trial?

The trial requires participants to switch to specific medications (sertraline, escitalopram, aripiprazole, or risperidone) if they haven't already done so within the last 2 weeks. This means you may need to stop your current medication if it's not one of these.

What prior data suggests that pharmacogenetics-informed pharmacotherapy is safe for psychiatric patients?

Research has shown that genetic testing to guide medication selection for mental health conditions is generally well-accepted. This testing helps doctors choose medications based on a person's genes, reducing the risk of side effects. Studies have found that patients who received medications chosen with genetic testing were more likely to experience positive outcomes, such as symptom relief, compared to those who did not. No specific reports of serious safety issues or negative effects have emerged from using this testing, suggesting that genetic testing is a safe option for managing mental health conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about pharmacogenomics-informed pharmacotherapy for psychiatric disorders because it personalizes medication recommendations based on an individual's genetic makeup. Unlike standard treatments that follow a one-size-fits-all approach, this method tailors drug choices and dosages to how a person metabolizes medications, potentially reducing side effects and improving effectiveness. This personalized approach could revolutionize psychiatric care by ensuring that patients receive the most suitable treatment faster, enhancing both safety and efficacy.

What evidence suggests that personalised medication advice based on pharmacogenetic testing could be effective for psychiatric disorders?

Research has shown that genetic testing to personalize medication can enhance treatment for mental health conditions. In this trial, participants in the PSY-PGx Group will receive personalized medication advice based on pharmacogenetic testing. Studies have found that this approach can lead to better symptom relief and reduce the risk of drug side effects. Evidence is particularly promising for treating mood, anxiety, and psychotic disorders. By understanding how a person's genes affect their reaction to medication, doctors can choose the most effective treatment with fewer trials and errors. ^{1 3 6 7 8}

Who Is on the Research Team?

Roos van Westrhenen, Ass. Prof.

Principal Investigator

Parnassia Psychiatric Institute (Amsterdam)

Roos van Westrhenen, Ass. Prof.

Principal Investigator

Parnassia Psychiatric Institute (Amsterdam)

Are You a Good Fit for This Trial?

This trial is for individuals aged 16-65 with mood, anxiety, or psychotic disorders who are switching to specific medications due to inadequate response or intolerance. Participants must be currently receiving psychiatric treatment and own a smartphone for monitoring. Exclusions include prior pharmacogenomic testing, certain medical conditions like liver disease, diabetes, cardiac issues, polypharmacy use, pregnancy/breastfeeding women, medication-naïve patients and substance abuse.

Inclusion Criteria

Ownership of a mobile phone (Android or iOS operation system) for passive monitoring

I have been diagnosed with a moderate to severe psychotic disorder.

Be able to understand the requirements of the study and provide written informed consent

Exclusion Criteria

My kidney function is reduced with an eGFR below 60.

I have a heart condition that affects my heart's electrical activity.

Severe somatic comorbidities

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pharmacogenetics-informed pharmacotherapy or dosing as usual for psychiatric disorders

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Personalised medication advice based on pharmacogenetic testing

Trial Overview The study tests personalized medication advice based on genetic testing against standard dosing in treating psychiatric disorders over 24 weeks. It's blinded and randomized: neither the participants nor the raters know who gets which treatment until after the results are collected.

How Is the Trial Designed?

Group I: PSY-PGx Group Experimental Treatment 1 Intervention

This is the intervention group. All patients will be treated according to a personalised medication recommendation based on the results of pharmacogenetic testing, following the prespecified dosing guideline. Prescribing physicians will prescribe one of the predefined drugs and will be unblinded for genotype and the resulting metabolisation phenotype.

Group II: Dosing as usual (DAU) group Active Control 1 Intervention

This is the control group. In this group, prescribing physicians will also prescribe one of the predefined drugs, but will remain blinded to their patients' genotype and resulting metabolism phenotype for the duration of their participation in the study. After the study, patients in the control group will also be given their pharmacogenetic profile, which will make it possible to personalise their medication if necessary.

Who Is Running the Clinical Trial?

Maastricht University Medical Center

Lead Sponsor

Trials

992

Recruited

3,304,000+

Maastricht University

Lead Sponsor

Trials

246

Recruited

13,190,000+

Ludwig-Maximilians - University of Munich

Collaborator

Trials

365

Recruited

210,000+

University of Bonn

Collaborator

Trials

64

Recruited

48,400+

State University of New York - Upstate Medical University

Collaborator

Trials

176

Recruited

27,600+

Babes-Bolyai University

Collaborator

Trials

48

Recruited

19,900+

Parnassia Psychiatric Institute

Collaborator

Trials

1

Recruited

2,500+

University of Barcelona

Collaborator

Trials

161

Recruited

63,200+

University of Belgrade

Collaborator

Trials

82

Recruited

55,600+

King's College London

Collaborator

Trials

772

Recruited

26,130,000+

Published Research Related to This Trial

Pharmacogenetic testing in psychiatry is not yet standard practice due to barriers like the lack of standardized testing panels and evidence-based recommendations, but there is a growing knowledgebase of gene-drug interactions relevant to psychiatric medications.

The proposed minimum gene and allele set for pharmacogenetic testing includes 16 variant alleles across five key genes (CYP2C9, CYP2C19, CYP2D6, HLA-A, HLA-B), which aims to help clinicians make informed decisions about medication selection and dosing for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards the integration of pharmacogenetics in psychiatry: a minimum, evidence-based genetic testing panel. Bousman, C., Maruf, AA., Müller, DJ.[2020]

Pharmacogenomics has the potential to significantly improve treatment outcomes in psychiatric disorders like depression and schizophrenia, where 30% to 50% of patients do not respond well to initial treatments.

Genetic variations in drug-metabolizing enzymes can influence both the effectiveness and side effects of psychiatric medications, but the integration of genetic testing into routine clinical practice remains limited and lacks clear guidelines for when it should be used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenetics and psychoactive drug therapy: ready for the patient? Steimer, W.[2010]

Pharmacogenetics can improve treatment outcomes for psychiatric disorders by tailoring medication choices based on patients' genetic profiles, particularly focusing on the CYP2C19 and CYP2D6 enzymes that affect drug metabolism.

A new clinical guideline from the Dutch Clinical Psychiatric Association recommends using genotyping to guide the selection and dosing of psychotropic medications, especially when patients experience side effects or treatment inefficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Policy and Practice Review: A First Guideline on the Use of Pharmacogenetics in Clinical Psychiatric Practice. van Westrhenen, R., van Schaik, RHN., van Gelder, T., et al.[2021]

In a study of 182 adult psychiatric patients, those whose treatment followed pharmacogenetic test recommendations had nearly four times higher odds of improvement compared to those who did not follow the recommendations.

The study found that following pharmacogenetic recommendations led to a significantly higher rate of stabilization in patients with more severe symptoms, without increasing the incidence of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenetic testing for the guidance of psychiatric treatment: a multicenter retrospective analysis. Espadaler, J., Tuson, M., Lopez-Ibor, JM., et al.[2022]

Pharmacogenetics has the potential to significantly improve psychiatric drug therapy, as psychotropic medications account for over one-third of drugs with available pharmacogenetic guidelines, yet its implementation in psychiatry remains limited.

Barriers to the use of pharmacogenetics in psychiatry include the complexity of drug metabolism and the classification of pharmacogenetic testing as only potentially beneficial, which may hinder its adoption despite the potential to reduce ineffective treatments and adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenetics in psychiatric care, a call for uptake of available applications. Lunenburg, CATC., Gasse, C.[2021]

Pharmacogenetics and pharmacogenomics aim to improve the understanding of how genetic factors influence individual responses to psychiatric medications, such as antidepressants and neuroleptics.

By developing predictive tools based on genetic information, personalized medicine in psychiatry could enhance treatment efficacy and reduce side effects, ultimately improving patient compliance and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenetics--genomics and personalized psychiatry. Möller, HJ., Rujescu, D.[2020]

Pharmacogenomic testing is becoming a standard practice in psychiatry, helping to predict how patients will respond to medications for depression and other psychiatric conditions.

These tests have been shown to improve treatment outcomes and reduce healthcare costs for patients who do not respond well to standard treatments, while ongoing research is identifying new gene variants that may further enhance personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenomics in Psychiatric Practice. El-Mallakh, RS., Roberts, RJ., El-Mallakh, PL., et al.[2019]

Most genetic variations that affect how patients respond to psychiatric medications are linked to drug metabolism genes, particularly CYP2C19 and CYP2D6, highlighting the importance of personalized treatment based on genetic profiles.

Recent studies involving over 1,000 patients have confirmed the clinical relevance of these genetic biomarkers, suggesting that integrating pharmacogenomics into psychiatric care could enhance treatment outcomes, though further large-scale trials are needed to assess the cost-effectiveness of such approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenomics of Antidepressant and Antipsychotic Treatment: How Far Have We Got and Where Are We Going? van Westrhenen, R., Aitchison, KJ., Ingelman-Sundberg, M., et al.[2020]

In a clinical trial involving 100 patients with major depressive disorder, pharmacogenomic-based antidepressant treatment (PGATx) showed a significant improvement in depression scores compared to standard treatment, with a mean difference of -4.1 points on the Hamilton Depression Rating Scale.

PGATx also demonstrated better tolerability, with fewer patients dropping out due to adverse events compared to those receiving standard treatment, suggesting it may be a safer option for managing depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial. Han, C., Wang, SM., Bahk, WM., et al.[2021]

Pharmacogenetic biomarkers, particularly those related to cytochrome enzymes, are now included in prescribing guidelines, marking a significant advancement towards precision psychiatry that personalizes depression treatment based on genetic information.

Integrating pharmacogenetic testing with therapeutic drug monitoring and other individual factors, such as symptom profiles and concomitant diseases, could optimize treatment outcomes, although challenges like staff training and infrastructure need to be addressed for widespread implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision psychiatry in clinical practice. Zanardi, R., Prestifilippo, D., Fabbri, C., et al.[2021]

Psychiatric disorders are complex and challenging to diagnose and treat due to overlapping symptoms, comorbidities, and varying patient responses to medications, highlighting the need for better diagnostic tools.

Pharmacogenetics could play a crucial role in personalizing psychiatric treatment by identifying biomarkers that improve diagnosis and predict treatment outcomes, potentially enhancing efficacy and reducing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the role of pharmacogenetics in clinical psychiatry? Lombard, J., Doraiswamy, PM.[2012]

Using pharmacogenetic testing to guide antidepressant treatment can improve response and tolerability in patients with major depressive disorder, as shown in a simulated trial with 100,000 subjects.

The cost-effectiveness of this approach becomes favorable when considering multiple treatment episodes, suggesting that incorporating genetic testing could be beneficial in clinical practice despite some limitations in the study design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A model to incorporate genetic testing (5-HTTLPR) in pharmacological treatment of major depressive disorders. Serretti, A., Olgiati, P., Bajo, E., et al.[2015]

Citations

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An Overview of Pharmacogenomic Testing for Psychiatric ... The results of the meta-analysis suggested that people who received therapy guided by pharmacogenomic testing experienced improved response rates and remission ...

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Utility of pharmacogenetic testing to optimise antidepressant ... In particular, the use of PGx testing in psychiatry has shown promising evidence in improving drug efficacy as well as reducing toxicity and ...

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Pharmacogenomics to support mental health medication ... With 4- to 6-week medication trials needed to evaluate clinical effectiveness, many available treatment options, and <50% response rates to ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0165032724007997

Effect of pharmacogenomic testing on the clinical treatment ... Pharmacogenomic testing is available to guide the treatment of depression. Pharmacogenomic guided medication enhances remission and response rates.

5. nature.com nature.com/articles/s44220-024-00240-2

A systematic review of pharmacogenetic testing to guide ... Here we conducted a systematic review to investigate whether pharmacogenetic testing in individuals undergoing antipsychotic treatment influences clinical or ...

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Pharmacogenetics Test - McGovern Medical School This essay explores the significance of pharmacogenetic testing in the context of psychiatric disorders, highlighting its potential to enhance treatment ...

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DNA Testing For Medications Pharmacogenomics testing for personalised medication treatment in areas such as mental health, pain management, cardiology & gastrointestinal.

8. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1276410/full

an umbrella review and updated meta-analysis Results: Patients who received PGx-guided medications were 41% to 78% more likely to achieve remission and 20% to 49% more likely to respond to ...