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

Trial Summary

What is the purpose of this trial?

A 24-week, patient- and rater-blinded, two-arm, parallel-group controlled, and multi-centre randomized clinical trial (RCT) to establish the benefits of pharmacogenetics-informed pharmacotherapy versus dosing as usual (DAU) in psychiatric patients suffering from mood, anxiety, or psychotic disorders.

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 data supports the idea that Pharmacogenomics-informed Pharmacotherapy for Psychiatric Disorders is an effective treatment?

The available research shows that using genetic information to guide psychiatric treatment can improve outcomes for patients. For example, recent large studies with over 1,000 patients have shown that genetic testing can help doctors choose the right medication, leading to better results and fewer side effects. This approach is more effective than the traditional trial-and-error method of prescribing drugs, which often leads to poor results and unwanted side effects. By using genetic testing, doctors can personalize treatment plans, making them more effective and improving patient satisfaction. ^{1 2 3 4 5}

What safety data exists for pharmacogenomics-informed pharmacotherapy in psychiatry?

Pharmacogenomics-informed pharmacotherapy in psychiatry is still in the early stages of implementation, with ongoing efforts to integrate it into clinical practice. Safety data primarily focuses on genetic variability in drug-metabolizing enzymes, particularly CYP2C19 and CYP2D6, which influence drug response and adverse effects. Clinical guidelines, such as those from the Dutch Clinical Psychiatric Association, recommend considering genotyping to address side effects or inefficacy. While promising, the clinical utility of pharmacogenomics in psychiatry requires further validation through large prospective trials to establish its safety and cost-effectiveness. ^{2 6 7 8 9}

Is personalized medication advice based on genetic testing a promising treatment for psychiatric disorders?

Yes, personalized medication advice based on genetic testing is promising because it can improve treatment outcomes for depression and other psychiatric disorders. It helps doctors choose the right medication for each person, reducing side effects and improving effectiveness. This approach can also lower healthcare costs by avoiding ineffective treatments. ^{1 2 10 11 12}

Research Team

Roos van Westrhenen, Ass. Prof.

Principal Investigator

Parnassia Psychiatric Institute (Amsterdam)

Roos van Westrhenen, Ass. Prof.

Principal Investigator

Parnassia Psychiatric Institute (Amsterdam)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pharmacogenetics--genomics and personalized psychiatry. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacogenomics of Antidepressant and Antipsychotic Treatment: How Far Have We Got and Where Are We Going? [2020]

3. England pubmed.ncbi.nlm.nih.gov

Precision psychiatry in clinical practice. [2021]

4. England pubmed.ncbi.nlm.nih.gov

What is the role of pharmacogenetics in clinical psychiatry? [2012]

5. United States pubmed.ncbi.nlm.nih.gov

Pharmacogenetic testing for the guidance of psychiatric treatment: a multicenter retrospective analysis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Towards the integration of pharmacogenetics in psychiatry: a minimum, evidence-based genetic testing panel. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Pharmacogenetics and psychoactive drug therapy: ready for the patient? [2010]

8. Ireland pubmed.ncbi.nlm.nih.gov

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

Policy and Practice Review: A First Guideline on the Use of Pharmacogenetics in Clinical Psychiatric Practice. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Pharmacogenomics in Psychiatric Practice. [2019]

11. England pubmed.ncbi.nlm.nih.gov

A model to incorporate genetic testing (5-HTTLPR) in pharmacological treatment of major depressive disorders. [2015]

12. Korea (South) 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. [2021]