Pharmacogenetic-Guided Treatment for Depression

(ADOPT PGx Trial)

Recruiting at 12 trial locations

Overseen By Deepak Voora, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must be taking: SSRIs

Disqualifiers: Psychosis, Dementia, Seizure, Bipolar, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

1461 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial helps doctors choose the best treatment for patients with depression by understanding how their bodies process medication, potentially improving symptoms more quickly.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should have recently started or revised SSRI therapy, or have an anticipated need for it, which suggests that continuing or adjusting current medications might be part of the study.

What data supports the effectiveness of the treatment Clinical decision support, Pharmacogenetic testing for depression?

Research shows that using pharmacogenetic testing to guide drug selection in depression can improve treatment outcomes. A meta-analysis found that this approach increased the odds of a positive clinical response by about 1.8 times compared to standard treatment, especially in patients with moderate to severe depression. ^{1 2 3 4 5}

Is pharmacogenetic testing safe for humans?

Pharmacogenetic testing is generally considered safe, but some studies suggest it may cause concerns for certain individuals, particularly those who are psychologically vulnerable. Additionally, there may be higher side effects for people with specific genetic profiles, like CYP2D6 poor metabolizers, when using certain medications. ^{1 2 6 7 8}

How does pharmacogenetic-guided treatment for depression differ from other treatments?

Pharmacogenetic-guided treatment for depression is unique because it uses genetic testing to help choose the most effective medication for each individual, potentially improving treatment outcomes compared to standard approaches that do not consider genetic factors. ^{1 3 5 9 10}

Research Team

Hrishikesh Chakraborty

Principal Investigator

Duke University

Josh F. Peterson, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for English or Spanish speakers aged 8 years and above with depression, who are starting or changing SSRI therapy at participating clinics. They must have had depressive symptoms for at least 3 months. Excluded are those too ill to consent, planning to move soon, with bipolar disorder, seizure disorders, certain genetic test results, psychosis, dementia or cognitive disabilities.

Inclusion Criteria

I have been diagnosed with depression.

I am 8 years old or older.

Patients followed at psychiatry clinics or primary care clinics at an enrolling site (such as, but not limited to, Internal Medicine, Family Medicine, or Pediatrics)

Exclusion Criteria

I am unable to understand or follow the study's procedures due to cognitive issues.

Have cognitive developmental delay and/or cognitive disability, including autism spectrum disorders (Note: ADHD is not an exclusion criteria)

I have a condition that causes seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either immediate pharmacogenetic testing and genotype-guided anti-depressant therapy or standard care with 6-month delayed pharmacogenetic testing

6 months

Regular visits as per trial protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Clinical decision support
• Pharmacogenetic testing

Trial Overview The Depression Trial compares immediate pharmacogenetic testing and tailored anti-depressant therapy against standard care with delayed testing. It aims to see if personalized treatment based on how a person's body processes SSRIs can better reduce depression symptoms.

Participant Groups

Group I: Depression - Immediate PGx Testing Experimental Treatment 2 Interventions

Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider

Group II: Depression - Delayed PGx Testing Experimental Treatment 1 Intervention

Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

University of Florida

Collaborator

Trials

1,428

Recruited

987,000+

Vanderbilt University Medical Center

Collaborator

Trials

922

Recruited

939,000+

Indiana University School of Medicine

Collaborator

Trials

194

Recruited

181,000+

Icahn School of Medicine at Mount Sinai

Collaborator

Trials

933

Recruited

579,000+

National Human Genome Research Institute (NHGRI)

Collaborator

Trials

273

Recruited

299,000+

Findings from Research

Pharmacogenomic testing in patients with major depressive disorder significantly improves response and remission rates at 8 and 12 weeks compared to standard treatment, with odds ratios indicating a 32% and 36% increase in response rates, respectively.

Patients receiving pharmacogenomic-guided treatment also experienced a notable reduction in medication changes within 30 days, suggesting that this approach leads to more consistent and effective treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of pharmacogenomics testing guiding on clinical outcomes in major depressive disorder: a systematic review and meta-analysis of RCT. Wang, X., Wang, C., Zhang, Y., et al.[2023]

The pharmacogenetic tool Neuropharmagen® significantly improves treatment outcomes for patients with depression, showing a 1.8-fold increase in the odds of clinical response compared to standard drug selection, based on a meta-analysis of 450 subjects.

In patients with moderate to severe depression, the effectiveness of pharmacogenetic-guided prescriptions is even greater, with an effect size of 0.42, indicating a 2.14-fold increase in the odds of response, suggesting this tool is particularly beneficial for more severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of a Pharmacogenetic Tool at Improving Treatment Efficacy in Major Depressive Disorder: A Meta-Analysis of Three Clinical Studies. Vilches, S., Tuson, M., Vieta, E., et al.[2020]

Pharmacogenetic-guided treatment for major depressive disorder (MDD) resulted in higher quality-adjusted life-years (QALYs) and lower costs compared to standard care, with a cumulative effect of 2.07 QALYs for the pharmacogenetic group versus 1.97 QALYs for standard care over three years.

The pharmacogenetic test (IDGx) not only improved treatment outcomes but also saved $2,918 in direct medical costs and $1,680 in indirect costs, particularly benefiting patients with severe depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of a Pharmacogenetic Test to Guide Treatment for Major Depressive Disorder. Groessl, EJ., Tally, SR., Hillery, N., et al.[2023]

The GeneSight pharmacogenomic test significantly increases the likelihood of response and remission in patients with major depression, showing over double the improvement in depressive symptoms compared to standard treatment after 10 weeks.

Patients identified with severe gene-drug interactions who switched to genetically suitable medications experienced a notable improvement in their symptoms, highlighting the test's potential to optimize antidepressant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder. Winner, JG., Carhart, JM., Altar, CA., et al.[2022]

In a study of 352 patients with depression, pharmacogenetic testing was able to predict the effectiveness of psychotherapeutic medications with a significant correlation (p < 0.001).

However, the same testing did not effectively predict side effect tolerability, indicating that while it can help in choosing effective treatments, it may not provide insights into how well patients will tolerate those treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenetic profile and major depressive and/or bipolar disorder treatment: a retrospective, cross-sectional study. Tonozzi, TR., Braunstein, GD., Kammesheidt, A., et al.[2022]

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]

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]

References

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

Effect of pharmacogenomics testing guiding on clinical outcomes in major depressive disorder: a systematic review and meta-analysis of RCT. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Pharmacogenetic tests to guide drug treatment in depression: Comparison of the available testing kits and clinical trials. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of a Pharmacogenetic Tool at Improving Treatment Efficacy in Major Depressive Disorder: A Meta-Analysis of Three Clinical Studies. [2020]

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

Cost-Effectiveness of a Pharmacogenetic Test to Guide Treatment for Major Depressive Disorder. [2023]

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

A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Pharmacogenetic profile and major depressive and/or bipolar disorder treatment: a retrospective, cross-sectional study. [2022]

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

Attitudes on pharmacogenetic testing in psychiatric patients with treatment-resistant depression. [2021]

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

Acceptability, Feasibility, and Utility of Integrating Pharmacogenetic Testing into a Child Psychiatry Clinic. [2022]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

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