Pharmacogenetic-Guided Antidepressants for Anxiety and Depression

(PGx-GAP Trial)

Overseen By Laina McAusland, MSc

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Must be taking: SSRIs

Disqualifiers: OCD, Psychosis, Bipolar, Autism, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

452 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it involves starting a new SSRI for depression or anxiety. It's best to discuss with the trial team or your doctor.

What data supports the effectiveness of pharmacogenetic-guided antidepressant prescribing for anxiety and depression?

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

Is pharmacogenetic-guided antidepressant treatment safe for humans?

Pharmacogenetic-guided antidepressant treatment is generally considered safe and can help reduce side effects by tailoring medication to individual genetic profiles. Studies suggest it can improve safety in psychiatric care by predicting potential risks, such as adverse reactions in certain patients, and help avoid toxic effects while maintaining treatment effectiveness. ^{1 6 7 8 9}

How is pharmacogenetic-guided antidepressant prescribing different from other treatments for anxiety and depression?

Pharmacogenetic-guided antidepressant prescribing is unique because it uses genetic testing to tailor antidepressant treatment to an individual's genetic makeup, potentially improving drug effectiveness and reducing side effects compared to standard treatments that do not consider genetic differences. ^{1 2 3 8 10}

What is the purpose of this trial?

This is a parallel arm randomized (1:1) controlled trial. Adolescents aged 12-17 years (n=452) who are starting or changing a selective serotonin reuptake inhibitor (SSRI) for depression and/or anxiety will be randomly allocated to receive 12-weeks of pharmacogenetic-guided antidepressant therapy (experimental intervention) or current prescribing guidelines/recommendations guided therapy (control intervention).

Research Team

Chad Bousman, PhD

Principal Investigator

University of Calgary

Amanda Newton, PhD

Principal Investigator

University of Alberta

Eligibility Criteria

Adolescents aged 12-17 with depression and/or anxiety starting or changing an SSRI medication can join. They must speak English fluently. Those with certain disorders like OCD, psychosis, bipolar disorder, eating disorders, autism spectrum disorder, fetal alcohol spectrum disorder, or intellectual disability cannot participate.

Inclusion Criteria

English fluency

I plan to start taking a new SSRI medication.

I am between 12 and 17 years old.

Exclusion Criteria

I have tried 3 or more SSRI medications without success.

I started or plan to start brain stimulation therapy soon after my referral.

Co-occurring obsessive compulsive disorder, psychosis, bipolar disorder, eating disorder, autism spectrum disorder, fetal alcohol spectrum disorder, or intellectual disability

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete baseline assessments and receive a one-time prescribing report

1 week

1 visit (in-person)

Treatment

Participants receive 12 weeks of pharmacogenetic-guided or guideline-based SSRI therapy

12 weeks

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pharmacogenetic-guided Antidepressant Prescribing

Trial Overview The trial is testing if using genetic information to guide antidepressant dosing (pharmacogenetic-guided) is better than the usual prescribing methods for treating depression and anxiety in adolescents over a period of 12 weeks.

Participant Groups

Group I: Experimental: Pharmacogenetic (PGx)-Guided Experimental Treatment 1 Intervention

Participants and their physician will receive a one-time prescribing report after completing baseline for selective serotonin reuptake inhibitors with dosing information based on CYP2B6, CYP2C19, and CYP2D6 genotype data, and clinical practice guidelines for fluoxetine as there are no pharmacogenetic guidelines for this medication.

Group II: Current Prescribing Guidelines/Recommendations Active Control 1 Intervention

Participants and their physician will receive a one-time prescribing report after completing baseline for selective serotonin reuptake inhibitors based on current prescribing guidelines/recommendations.

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Findings from Research

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]

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]

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]

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]

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 study of 224 psychiatric patients, pharmacogenetic testing for the CYP2D6 gene revealed that bipolar patients with poor metabolizer status experienced maniac switching when prescribed selective serotonin reuptake inhibitors, indicating a significant safety concern.

The findings suggest that pharmacogenetic testing could be a valuable tool in predicting adverse effects in psychiatric patients, particularly for those at risk of affective switching when treated with CYP2D6 substrates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Pharmacogenetics in Improving the Safety of Psychiatric Care by Predicting the Potential Risks of Mania in CYP2D6 Poor Metabolizers Diagnosed With Bipolar Disorder. Sánchez-Iglesias, S., García-Solaesa, V., García-Berrocal, B., et al.[2022]

Pharmacogenetic testing for genes like CYP2D6 and CYP2C19 can help personalize antidepressant treatment, potentially improving effectiveness and reducing side effects for patients with major depressive disorder.

The article discusses how understanding genetic variations can lead to better pharmacotherapeutic recommendations, enhancing patient outcomes beyond what is achieved through standard clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Pharmacogenetic Prescribing Guidelines for Antidepressants: A Template for Psychiatric Precision Medicine. Nassan, M., Nicholson, WT., Elliott, MA., et al.[2022]

Pharmacogenetic testing for the CYP2C19 and CYP2D6 genes can help tailor antidepressant therapy, potentially reducing adverse effects and improving treatment outcomes for psychiatric patients.

The French National Network of Pharmacogenetics recommends these tests as a useful tool in optimizing antidepressant treatment, highlighting their role in personalizing medication based on individual genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenetics of antidepressant drugs: State of the art and clinical implementation - recommendations from the French National Network of Pharmacogenetics. Quaranta, S., Dupouey, J., Colle, R., et al.[2017]

Genetic factors significantly influence how antidepressants are processed in the body, affecting their effectiveness and safety, which can be identified through modern genotyping methods.

Adjusting antidepressant dosages based on individual genetic variants, particularly those affecting drug-metabolizing enzymes like cytochrome P450, can improve treatment outcomes and tolerance for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The value of pharmacogenetic tests in antidepressive medication therapy]. Kirchheiner, J., Sasse, J., Roots, I., et al.[2018]

References

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

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

2. 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]

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

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

5. 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]

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

Role of Pharmacogenetics in Improving the Safety of Psychiatric Care by Predicting the Potential Risks of Mania in CYP2D6 Poor Metabolizers Diagnosed With Bipolar Disorder. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Pharmacogenetic Prescribing Guidelines for Antidepressants: A Template for Psychiatric Precision Medicine. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Pharmacogenetics of antidepressant drugs: State of the art and clinical implementation - recommendations from the French National Network of Pharmacogenetics. [2017]

10. Germany pubmed.ncbi.nlm.nih.gov

[The value of pharmacogenetic tests in antidepressive medication therapy]. [2018]