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

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.

Inclusion Criteria:

1. Age 15-64;

2. Diagnostic and Statistical Manual Diploma in Social Medicine diagnosis of
schizophrenia (DSM IV), schizoaffective disorder, schizophreniform disorder, psychotic
disorder NOS, and bipolar disorder;

3. Onset of antipsychotic treatment within the past 3 years;

4. Able to provide informed consent. (assent for those under age 18)

Exclusion Criteria:

1. Evidence of serious medical conditions,

2. Female patients who are pregnant or breast feeding;

3. Patients who are not willing to take medications for treatment;

4. Patients who are unable to provide informed consent due to impairment in
decision-making ability.