Pharmacogenetic-Guided Antidepressants for Anxiety and Depression
(PGx-GAP Trial)
Recruiting in Palo Alto (17 mi)
Overseen ByChad Bousman, PhD
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Calgary
Must be taking: SSRIs
Disqualifiers: OCD, Psychosis, Bipolar, Autism, others
No Placebo Group
Trial Summary
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).
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.
12345Is 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.
16789How 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.
123810Eligibility 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.
+1 more
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
+2 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Experimental: Pharmacogenetic (PGx)-GuidedExperimental Treatment1 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/RecommendationsActive Control1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of CalgaryCalgary, Canada
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Who Is Running the Clinical Trial?
University of CalgaryLead Sponsor
References
A model to incorporate genetic testing (5-HTTLPR) in pharmacological treatment of major depressive disorders. [2015]To evaluate the benefit of pharmacogenetics in antidepressant treatment.
A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial. [2021]Pharmacogenomic-based antidepressant treatment (PGATx) may result in more precise pharmacotherapy of major depressive disorder (MDD) with better drug therapy guidance.
Effectiveness of a Pharmacogenetic Tool at Improving Treatment Efficacy in Major Depressive Disorder: A Meta-Analysis of Three Clinical Studies. [2020]Several pharmacogenetic tests to support drug selection in psychiatric patients have recently become available. The current meta-analysis aimed to assess the clinical utility of a commercial pharmacogenetic-based tool for psychiatry (Neuropharmagen®) in the treatment management of depressive patients. Random-effects meta-analysis of clinical studies that had examined the effect of this tool on the improvement of depressive patients was performed. Effects were summarized as standardized differences between treatment groups. A total of 450 eligible subjects from three clinical studies were examined. The random effects model estimated a statistically significant effect size for the pharmacogenetic-guided prescription (d = 0.34, 95% CI = 0.11-0.56, p-value = 0.004), which corresponded to approximately a 1.8-fold increase in the odds of clinical response for pharmacogenetic-guided vs. unguided drug selection. After exclusion of patients with mild depression, the pooled estimated effect size increased to 0.42 (95% CI = 0.19-0.65, p-value = 0.004, n = 287), corresponding to an OR = 2.14 (95% CI = 1.40-3.27). These results support the clinical utility of this pharmacogenetic-based tool in the improvement of health outcomes in patients with depression, especially those with moderate-severe depression. Additional pragmatic RCTs are warranted to consolidate these findings in other patient populations.
A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder. [2022]A prospective double-blind randomized control trial (RCT) to evaluate the benefit of a combinatorial, five gene pharmacogenomic test and interpretive report (GeneSight) for the management of psychotropic medications used in the treatment of major depression in an outpatient psychiatric practice.
Effect of pharmacogenomics testing guiding on clinical outcomes in major depressive disorder: a systematic review and meta-analysis of RCT. [2023]Pharmacogenomic testing guided treatment have been developed to guide drug selection or conversion in major depressive disorder patients. Whether patients benefit from pharmacogenetic testing remains unclear. We aim to evaluates the effect of pharmacogenomic testing guiding on clinical outcomes of major depressive disorder.
Pharmacogenetic profile and major depressive and/or bipolar disorder treatment: a retrospective, cross-sectional study. [2022]To compare pharmacogenetic test predictions with self-reported treatment experience and side effect tolerability among patients with depression taking psychotherapeutic medications.
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]One of the main concerns in psychiatric care is safety related to drug management. Pharmacogenetics provides an important tool to assess causes that may have contributed the adverse events during psychiatric therapy. This study illustrates the potential of pharmacogenetics to identify those patients for which pharmacogenetic-guided therapy could be appropriate. It aimed to investigate CYP2D6 genotype in our psychiatric population to assess the value of introducing pharmacogenetics as a primary improvement for predicting side effects.A broad series of 224 psychiatric patients comprising psychotic disorders, depressive disturbances, bipolar disorders, and anxiety disorders was included. The patients were genotyped with the AmpliChip CYP450 Test to analyzing 33 allelic variants of the CYP2D6 gene.All bipolar patients with poor metabolizer status showed maniac switching when CYP2D6 substrates such as selective serotonin reuptake inhibitors were prescribed. No specific patterns were identified for adverse events for other disorders.We propose to utilize pharmacogenetic testing as an intervention to aid in the identification of patients who are at risk of developing affective switching in bipolar disorder treated with selective serotonin reuptake inhibitors, CYP2D6 substrates, and inhibitors.
Pharmacokinetic Pharmacogenetic Prescribing Guidelines for Antidepressants: A Template for Psychiatric Precision Medicine. [2022]Antidepressants are commonly prescribed medications in the United States, and there is increasing interest in individualizing treatment selection for more than 20 US Food and Drug Administration-approved treatments for major depressive disorder. Providing greater precision to pharmacotherapeutic recommendations for individual patients beyond the large-scale clinical trials evidence base can potentially reduce adverse effect toxicity profiles and increase response rates and overall effectiveness. It is increasingly recognized that genetic variation may contribute to this differential risk to benefit ratio and thus provides a unique opportunity to develop pharmacogenetic guidelines for psychiatry. Key studies and concepts that review the rationale for cytochrome P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19) genetic testing can be delineated by serum levels, adverse events, and clinical outcome measures (eg, antidepressant response). In this article, we report the evidence that contributed to the implementation of pharmacokinetic pharmacogenetic guidelines for antidepressants primarily metabolized by CYP2D6 and CYP2C19.
Pharmacogenetics of antidepressant drugs: State of the art and clinical implementation - recommendations from the French National Network of Pharmacogenetics. [2017]Tailoring antidepressant drug therapy to each individual patient is a complex process because these drugs have adverse effects leading to discontinuation. Pharmacogenetics may provide useful information in routine practice for optimizing antidepressant treatment by helping limit toxic effects while maintaining efficacy. This review presents the usefulness of pharmacogenetic tests for P450 cytochromes CYP2C19 and CYP2D6 in psychiatric patients taking antidepressants. Depending on the level of evidence, the French National Network of Pharmacogenetics (RNPGx) has issued recommendations stating that pharmacogenetic tests for CYP2D6 and CYP2C19 genes are potentially useful in psychiatric patients treated with antidepressant drugs.
[The value of pharmacogenetic tests in antidepressive medication therapy]. [2018]The pharmacokinetics and effect of antidepressants are influenced by genetic factors. Modern methods of genotyping allow fast and inexpensive identification of genetic variants and thus can be used in clinical diagnostics to improve the tolerance to drug therapy. Numerous studies have investigated the significance of genetic variants in drug-metabolizing enzymes, drug and natural substrate transporters, neurotransmitter receptors, and molecules involved in signal transduction. While the interindividual differences in oral clearance, half-life, and bioavailability caused by genetic variants in the cytochrome P450 liver enzymes can be overcome by individual adjustment of dosage according to certain genotypes, the effects of genetic variants in antidepressive target structures are more difficult to translate into clinical recommendations. This article gives an overview of the currently available literature and points to situations in which the determination of pharmacogenetic variants might change drug therapy or therapeutic strategies for the individual patient. Dose adjustments for common antidepressant drugs based upon differences in pharmacokinetic parameters caused by genetic variability will be given.