Prospective Pharmacogenetic Testing and Clinical Outcomes in Patients With Early-Phase Psychosis

Study Overview
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Brief Summary
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This study evaluates whether prospective pharmacogenetic testing is cost-effective in affecting clinical treatment outcomes in patients with early-phase psychosis.

Detailed Description
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Large scale clinical trials have demonstrated that a substantial proportion of patients with psychotic disorders, such as schizophrenia and bipolar disorder, discontinue their antipsychotic medications due to either lack of efficacy or intolerable side effects, such as extrapyramidal symptoms (EPS) and weight gain. In clinical practice, it is essentially a trial and error process in deciding the best antipsychotic drug to start or switch to after a failed trial as there is little empirical data available to guide clinicians in drug selection. One promising tool, which can potentially provide valuable information to help guide medication management, is pharmacogenetic testing of certain genetic variants that are associated with psychiatric drug response. However, most pharmacogenetic studies to date have been retrospective, and there is no prospective clinical trial evaluating the clinical utility of pharmacogenetic testing in guiding clinical practice. Furthermore, it is unknown whether pharmacogenetic testing is cost effective. Until recently, pharmacogenetic testing has been expensive and time-consuming. New technology in the past few years makes it possible for cheaper and faster testing. One of the companies that offer pharmacogenetic testing services, Genomind LLC, provides genotyping of variants (GeneceptTM Assay) that are relevant to psychiatric drug response. For example, the serotonin 2C receptor gene (HTR2C) has variants that protect patients from antipsychotic drug induced weight gain (-759C/T, rs3813929); a deletion variant of the dopamine D2 receptor gene (DRD2) suggests poor efficacy with antipsychotic drug treatment (-141C Ins/Del, rs1799732); the short allele of the serotonin transporter gene (SLC6A4) is associated with antidepressant side effects. In the present study, investigators propose to conduct a prospective, randomized, rater-blinded clinical trial to test the clinical utility and cost-effectiveness of pharmacogenetic testing in guiding medication treatment in patients with recent-onset psychotic disorders. Patients will be assigned to either a pharmacogenetic testing guided treatment condition (PGT) or a treatment as usual condition (TAU). In the PGT condition, patients will utilize the GeneceptTM Assay and results will be provided to their prescribers who may use the results to guide medication management. In the TAU condition, patients will also utilize the GeneceptTM Assay but the results will not be provided back to their prescribers, who will treat the patients without the knowledge of pharmacogenetic testing results. Pharmacogenetic testing may be more relevant in recent-onset or early stage illnesses because past medication history that is typically used to guide medication choice may not be available. Pharmacogenomic testing may be particularly pertinent to younger patients because they tend to be medication naïve and do not have previous medication history to guide future treatment. Pharmacogenomic testing may provide valuable information to guide medication choice in clinical practice.

Official Title
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Prospective Pharmacogenetic Testing and Clinical Outcomes in Patients With Early-Phase Psychosis

Conditions
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Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, Psychotic Disorders, Bipolar Disorder

Intervention / Treatment
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* Biological: PGx testing guided treatment (PGT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 15-64; Diagnostic and Statistical Manual Diploma in Social Medicine diagnosis of schizophrenia (DSM IV), schizoaffective disorder, schizophreniform disorder, psychotic disorder NOS, and bipolar disorder; Onset of antipsychotic treatment within the past 3 years; Able to provide informed consent. (assent for those under age 18) Exclusion Criteria: Evidence of serious medical conditions, Female patients who are pregnant or breast feeding; Patients who are not willing to take medications for treatment; Patients who are unable to provide informed consent due to impairment in decision-making ability.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PGx testing guided treatment (PGT)<br>Results of the GeneceptTM Assay will be provided to their prescribers who may use the knowledge to guide medication management. | Biological: PGx testing guided treatment (PGT)<br>* Genecept Assay (GeneceptTM Assay) will provide information on genotypes of genetic variants that are relevant to psychiatric drug response. The provider can use the information to decide on which psychotropic drugs to use.<br>|
| No Intervention: Treatment as usual condition (TAU)<br>Patients will also utilize the GeneceptTM Assay but the results will not be provided back to their prescribers, who will treat the patients without the knowledge of pharmacogenetic testing results. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Discontinuation of First Medication | Due to lack of efficacy or intolerability | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prescribing Behavior Change Based on the Results of the Pharmacogenetic Testing | The clinician is asked to fill out a questionnaire elaborating the medication decision-making process for each patient, including whether or not acting on the genetic information provided clinically relevant information. | 12 months |