SAMPLE REPORT MENTAL HEALTH DNA INSIGHT LABORATORY INFO. Protected Health Information. SSRIs. TCAs. Other Antidepressants

Transcription

1 Test Results Reviewed & Approved by: Laboratory Director, Nilesh Dharajiya,.D. ENTAL HEALTH DNA INSIGHT PERSONAL DETAILS DOB Jan 1, 19XX ETHNICITY Caucasian ORDERING HEALTHCARE PROFESSIONAL Glenn Braunstein.D Nexus Center Drive San Diego, CA US LABORATORY INFO ACCESSION NUBER ACTIVATION CODE SPECIEN TYPE COLLECTED DATE G PGTST-NTAB SALIVA Feb 19, 2016 RECEIVED DATE Feb 22, 2016 Drug Class Drug Preferential Use Use As Directed ay Have Significant Limitations ay Cause Serious Adverse Events Citalopram Escitalopram Fluoxetine SSRIs Fluvoxamine Paroxetine Sertraline Vilazodone Amitriptyline Clomipramine Desipramine TCAs Doxepin Imipramine Nortriptyline Protriptyline Trimipramine Bupropion Buspirone Duloxetine Levomilnacipran Other Antidepressants irtazapine Nefazodone Trazodone Venlafaxine Vortioxetine Laboratory Director: Nilesh Dharajiya,.D. CLIA Number: 05D Nexus Center Drive, San Diego, CA PAGE 1 of 11

2 ENTAL HEALTH DNA INSIGHT Drug Class Drug Preferential Use Use As Directed ay Have Significant Limitations ay Cause Serious Adverse Events Aripiprazole Asenapine Clozapine Iloperidone Atypical Antipsychotics Lurasidone Olanzapine Paliperidone Quetiapine Risperidone Ziprasidone Haloperidol Perphenazine Typical Antipsychotics Pimozide Thioridazine Zuclopenthixol Carbamazepine Divalproex ood Stabilizers Lamotrigine Oxcarbazepine Phenytoin Valproic acid Norepinephrine Reuptake Inhibitor Atomoxetine Alprazolam Benzodiazepines Clobazam Diazepam Dextromethorphan and Quinidine Others Galantamine odafinil Tetrabenazine Laboratory Director: Nilesh Dharajiya,.D. CLIA Number: 05D Nexus Center Drive, San Diego, CA PAGE 2 of 11

3 ENTAL HEALTH DNA INSIGHT Drug Class Drug Comments SSRIs Citalopram ay Cause Serious Adverse Events Patient's genotype is associated with greatly reduced metabolism of citalopram compared to extensive metabolizers, which may increase the risk of adverse effects. Alternative medications that are not primarily metabolized by the CYP2C19 enzyme should be considered. Reduction of the starting dose is recommended if treatment of citalopram is warranted. The SLC6A4 alleles found in this patient cannot determine the benefit or limitation of the use of SSRI antidepressants. Escitalopram Sertraline Patient's genotype is associated with greatly reduced metabolism of escitalopram compared to extensive metabolizers, which may increase the risk of adverse effects. Alternative medications that are not primarily metabolized by the CYP2C19 enzyme should be considered. Reduction of the starting dose is recommended if treatment of escitalopram is warranted. Patient's genotype is associated with greatly reduced metabolism of sertraline compared to extensive metabolizers, which may increase the risk of adverse effects. Alternative medications that are not primarily metabolized by the CYP2C19 enzyme should be considered. Reduction of the starting dose is recommended if treatment of sertraline is warranted. Other Antidepressants Venlafaxine Patient's genotype is associated with increased plasma concentrations of venlafaxine at standard doses, which may increase risk of adverse effects. Consider alternative medications that are not primarily metabolized by the CYP2D6 enzyme. The SLC6A4 alleles found in this patient cannot determine the benefit or limitation of the use of SSRI antidepressants. Atypical Antipsychotics Risperidone Patient's genotype is associated with an increased plasma risperidone:9-oh-risperidone ratio, which may increase the risk of adverse effects. Consider an alternative drug or monitor patient for adverse events and adjust dosage accordingly. Typical Antipsychotics Thioridazine Patient's genotype is associated with decreased CYP2D6 enzyme activity. The CYP2D6 enzyme contributes to the clearance of cardiotoxic thioridazine and is inhibited by the drug. Thioridazine is contraindicated in patients with reduced CYP2D6 enzyme activity. Laboratory Director: Nilesh Dharajiya,.D. CLIA Number: 05D Nexus Center Drive, San Diego, CA PAGE 3 of 11

4 ENTAL HEALTH DNA INSIGHT Drug Class Drug Comments ood Stabilizers Carbamazepine ay Cause Serious Adverse Events (Continued) Patient's risk of developing carbamazepine hypersensitivity cannot be determined from the genotype results. It cannot be determined whether or not this patient has the HLA- B*1502 allele that is associated with serious skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, if treated with carbamazepine. The genetic test for this condition is most applicable to patients of Han Chinese descent. If clinically indicated, patients of Asian descent, including Han Chinese who receive an "Unknown" outcome, could be advised to undergo HLA sequencing to assess their risk of carbamazepine hypersensitivity. Other HLA alleles have been shown to be associated with carbamazepine hypersensitivity in people of Caucasian and Japanese descent, in whom HLA-B*1502 is largely absent. Lamotrigine Oxcarbazepine Phenytoin Patient's risk of developing severe cutaneous adverse reactions to lamotrigine cannot be determined from the genotype results. It cannot be determined whether or not this patient has the HLA-B*1502 allele that has been reported in patients who developed serious skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, when treated with lamotrigine. The genetic test for this condition is most applicable to patients of Han Chinese descent. If clinically indicated, patients of Asian descent, including Han Chinese who receive an "Unknown" outcome, could be advised to undergo HLA sequencing to assess their risk of lamotrigine hypersensitivity. Other HLA alleles have been shown to be associated with lamotrigine hypersensitivity in people of Caucasian and Japanese descent, in whom HLA-B*1502 is largely absent. Patient's risk of developing oxcarbazepine hypersensitivity cannot be determined from the genotype results. It cannot be determined whether or not this patient has the HLA-B*1502 allele that is associated with serious skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, if treated with oxcarbazepine. The genetic test for this condition is most applicable to patients of Han Chinese descent. If clinically indicated, patients of Asian descent, including Han Chinese who receive an "Unknown" outcome, could be advised to undergo HLA sequencing to assess their risk of oxcarbazepine hypersensitivity. Other risk factors may contribute to oxcarbazepine hypersensitivity in people of Caucasian and Japanese descent, in whom HLA-B*1502 is largely absent. Patient's risk of developing phenytoin hypersensitivity cannot be determined from the genotype results. It cannot be determined whether or not this patient has the HLA-B*1502 allele, which is associated with serious skin reactions, such as Stevens-Johnson syndrome or toxic epidermal Necrolysis (SJS/TEN), when treated with phenytoin. This genetic test is most applicable to patients of Han Chinese descent. If clinically indicated, patients of Asian descent, including Han Chinese who receive an Unknown outcome, may be advised to undergo HLA sequencing to assess their risk of phenytoin hypersensitivity. There are insufficient data to associate this allele with phenytoin hypersensitivity in other ethnicities. This patient's genotype is associated with low CYP2C9 enzyme activity; therefore, the patient may have increased plasma concentrations of phenytoin compared to most patients treated with the same dose. Some studies report an association between this patient's genotype and increased risk of phenytoin toxicity. Symptoms of toxicity include dizziness, nystagmus, ataxia and mental confusion, among others. A reduced dose, monitoring of serum phenytoin concentrations and/or alertness for signs of toxicity could be considered. Laboratory Director: Nilesh Dharajiya,.D. CLIA Number: 05D Nexus Center Drive, San Diego, CA PAGE 4 of 11

5 ENTAL HEALTH DNA INSIGHT Drug Class Drug Comments SSRIs Fluvoxamine ay Have Significant Limitations The SLC6A4 alleles found in this patient cannot determine the benefit or limitation of the use of SSRI antidepressants. Patient's genotype is associated with reduced metabolism of fluvoxamine compared to extensive metabolizers, which may increase the risk of adverse effects. Reduction of the starting dose is recommended. There are no specific recommendations on dose adjustments. Paroxetine Patient's genotype is associated with reduced metabolism of paroxetine compared to extensive metabolizers, which may increase the risk of adverse effects. Reduction of the starting dose is recommended. There are no specific recommendations on dose adjustments. TCAs Other Antidepressants Atypical Antipsychotics Amitriptyline Clomipramine Desipramine Doxepin Imipramine Nortriptyline Trimipramine Duloxetine irtazapine Vortioxetine Aripiprazole Iloperidone The SLC6A4 alleles found in this patient cannot determine the benefit or limitation of the use of SSRI antidepressants. Patient's genotype is associated with greatly reduced metabolism of TCAs compared to extensive metabolizers, which may increase the risk of adverse effects. edications other than TCAs should be considered. Therapeutic drug monitoring is recommended to guide dose adjustments if tricyclic treatment is warranted. Patient's genotype is associated with greatly reduced metabolism of TCAs compared to extensive metabolizers, which may increase the risk of adverse effects. Reduction of the starting dose and the use of therapeutic drug monitoring are recommended. Patient's genotype is associated with greatly reduced metabolism of TCAs compared to extensive metabolizers, which may increase the risk of adverse effects. edications other than TCAs should be considered. Therapeutic drug monitoring is recommended to guide dose adjustments if tricyclic treatment is warranted. Patient's genotype is associated with greatly reduced metabolism of TCAs compared to extensive metabolizers, which may increase the risk of adverse effects. Reduction of the starting dose and the use of therapeutic drug monitoring are recommended. Patient's genotype is associated with greatly reduced metabolism of TCAs compared to extensive metabolizers, which may increase the risk of adverse effects. edications other than TCAs should be considered. Therapeutic drug monitoring is recommended to guide dose adjustments if tricyclic treatment is warranted. Patient may have increased plasma concentrations of duloxetine at standard doses. Patient may have increased plasma concentrations of mirtazapine; though it is unclear if increased plasma concentrations of mirtazapine influences therapeutic benefits or the risk of adverse effects. Patient's genotype is associated with decreased oral clearance of vortioxetine compared to CYP2D6 extensive metabolizers. Due to the lack of clinical evidence, there are no specific recommendations on dose adjustment of vortioxetine. Patient's genotype is associated with increased plasma concentrations of aripiprazole at standard doses. Patient may have increased plasma concentrations of iloperidone and its active metabolite. Laboratory Director: Nilesh Dharajiya,.D. CLIA Number: 05D Nexus Center Drive, San Diego, CA PAGE 5 of 11

6 ENTAL HEALTH DNA INSIGHT Drug Class Drug Comments Typical Antipsychotics Haloperidol ay Have Significant Limitations (Continued) Patient's genotype is consistent with decreased CYP2D6 activity, and the patient may have increased plasma concentrations of a haloperidol metabolite known as reduced haloperidol. Accumulation of haloperidol and reduced haloperidol in the blood are associated with increased risk of adverse effects. Norepinephrine Reuptake Inhibitor Benzodiazepines Perphenazine Zuclopenthixol Atomoxetine Clobazam Diazepam Patient's genotype is associated with increased plasma concentrations of perphenazine, which may increase the risk of adverse effects. Patient may have increased plasma concentrations of zuclopenthixol, which may increase the risk of adverse effects. Consider reducing the dose by 25% or consider alternative medications. Patient's genotype is associated with increased plasma concentrations and slower elimination of atomoxetine. Due to the lack of clinical evidence, there are no specific recommendations on dose adjustment of atomoxetine. Patient's genotype is associated with increased plasma concentrations of a clobazam's active metabolite, N-desmethylclobazam, compared to CYP2C19 extensive metabolizers. Based on the FDA-approved drug label, clobazam dosage may need to be adjusted. Patient's genotype is associated with increased plasma concentrations and slower clearance of diazepam compared to CYP2C19 extensive metabolizers. Due to the lack of clinical evidence, there are no specific recommendations on dose adjustment of diazepam. Drug Class Drug Comments Atypical Antipsychotics Asenapine Preferential Use asenapine. Clozapine Lurasidone Olanzapine Paliperidone Quetiapine Ziprasidone clozapine. lurasidone. olanzapine. paliperidone. quetiapine. ziprasidone. Laboratory Director: Nilesh Dharajiya,.D. CLIA Number: 05D Nexus Center Drive, San Diego, CA PAGE 6 of 11

7 ENTAL HEALTH DNA INSIGHT Drug Class Drug Comments SSRIs Fluoxetine Use As Directed The SLC6A4 alleles found in this patient cannot determine the benefit or limitation of the use of SSRI antidepressants. Vilazodone The most recent label for this drug should be consulted for up-to-date dosing guidelines TCAs Protriptyline The most recent label for this drug should be consulted for up-to-date dosing guidelines Other Antidepressants Bupropion Buspirone Levomilnacipran Nefazodone Trazodone The most recent label for this drug should be consulted for up-to-date dosing guidelines Typical Antipsychotics Pimozide The most recent label for this drug should be consulted for up-to-date dosing guidelines ood Stabilizers Divalproex Valproic acid The most recent label for this drug should be consulted for up-to-date dosing guidelines Benzodiazepines Alprazolam The most recent label for this drug should be consulted for up-to-date dosing guidelines Others Dextromethorphan and Quinidine Galantamine odafinil Tetrabenazine The most recent label for this drug should be consulted for up-to-date dosing guidelines Laboratory Director: Nilesh Dharajiya,.D. CLIA Number: 05D Nexus Center Drive, San Diego, CA PAGE 7 of 11

8 ENTAL HEALTH DNA INSIGHT GENOTYPE/HAPLOTYPE DETAIL PHARACOGENETICS This section lists the genetic markers that were tested. Results are organized by gene. Each gene has up to three sections, which may include a "etabolizer Status" section, a "Genetic Result" section and an associated table with three columns. "etabolizer Status" indicates the patient's predicted metabolizer status. "Genetic Result" indicates the haplotype, genotype or presence of a mutation. A genetic result that contains ND indicates that a haplotype could not be determined. Unable To Report indicates that no result can be provided. In the tables, results are organized by gene in three columns: 1. Gene/Locus refers to the gene or intergenic region where the marker is located. 2. arker refers to the unique identifier of the tested marker. 3. Genotype refers to the combination of nucleotides at a particular marker. The letter(s) on each side of the slash refer(s) to the two copies of the patient s DNA. "Del" indicates a deletion of the nucleotide(s) in the patient's DNA. A genotype of - - indicates that a result could not be obtained. CYP1A2 CYP1A2 rs A/C CYP2B6 etabolizer Status: Extensive etabolizer Genetic Result: CYP2B6 *1/*4 CYP2B6 rs A/G CYP2B6 rs C/C CYP2B6 rs G/G CYP2B6 rs C/C CYP2B6 rs A/A CYP2C19 etabolizer Status: Poor etabolizer Genetic Result: CYP2C19 *2/*8 CYP2C19 rs G/A CYP2C19 rs G/G CYP2C19 rs C/C CYP2C19 rs A/A CYP2C19 rs T/C CYP2C19 rs C/C CYP2C19 rs G/G CYP2C19 rs T/T CYP2C9 etabolizer Status: Intermediate etabolizer Genetic Result: CYP2C9 *1/*3 CYP2C9 rs A/C CYP2C9 rs C/C CYP2C9 rs A/A CYP2D6 etabolizer Status: Intermediate etabolizer Genetic Result: CYP2D6 *4/*10 CYP2D6 rs16947 C/C CYP2D6 rs G/G CYP2D6 rs T/T CYP2D6 rs C/C CYP2D6 rs G/A CYP2D6 rs T/T CYP2D6 rs AAG/AAG CYP2D6 rs G/G CYP2D6 rs C/C CYP2D6 rs C/C CYP2D6 rs A/A CYP2D6 rs C/C CYP2D6 rs G/G CYP2D6 rs A/A CYP2D6 rs C/C CYP2D6 rs T/T CYP3A4 CYP3A4 rs A/A CYP3A4 rs C/C CYP3A4 rs C/C CYP3A4 rs A/A CYP3A4 rs A/A CYP3A4 rs C/C CYP3A5 etabolizer Status: Expressor Genetic Result: CYP3A5 *1/*1 CYP3A5 rs T/T DRD2 DRD2 rs C/del HLA-A Genetic Result: HLA-A x/x HLA Region rs A/A HLA-B Genetic Result: HLA-B x/x or *1502/x HLA Region rs C/T HLA Region rs G/C Laboratory Director: Nilesh Dharajiya,.D. CLIA Number: 05D Nexus Center Drive, San Diego, CA PAGE 8 of 11

9 ENTAL HEALTH DNA INSIGHT HTR2A HTR2A rs G/G HTR2A HTR2A rs6311 A/G HTR2C HTR2C rs G/G HTR2C rs G/A POLG POLG rs G/G POLG rs G/G POLG rs G/G SLC6A4 Genetic Result: Unknown SLC6A4 Haplotype SLC6A4 5-HTTLPR S/L SLC6A4 rs25531 A/G UGT1A4 UGT1A4 rs A/A Laboratory Director: Nilesh Dharajiya,.D. CLIA Number: 05D Nexus Center Drive, San Diego, CA PAGE 9 of 11

10 ENTAL HEALTH DNA INSIGHT TEST ETHODOLOGY Genotyping by PCR-based enrichment and next-generation sequencing or by array-based evaluation of multiple molecular probes. DISCLAIER This test was developed and its performance characteristics determined by Pathway Genomics Corporation. It has not been cleared or approved by the FDA. The laboratory is regulated under CLIA as qualified to perform high-complexity testing. This test is used for clinical purposes. It should not be regarded as investigational or for research. If you have any questions about this report or wish to speak with one of Pathway Genomics' genetic counselors, please call (877) RISKS AND LIITATIONS Risk of Laboratory Technical Problems or Laboratory Error The certified testing laboratory has standard and effective procedures in place to protect against technical and operational problems. However, such problems may still occur. The testing laboratory receives samples collected by patients and physicians. Problems in shipping to the laboratory or sample handling can occur, including but not limited to damage to the specimen or related paperwork, mislabeling, and loss or delay of receipt of the specimen. Laboratory problems can occur that might lead to inability to obtain results. Examples include, but are not limited to, sample mislabeling, DNA contamination, un-interpretable results, and human and/or testing system errors. In such cases, the testing laboratory may need to request a new sample. However, upon re-testing, results may still not be obtainable. As with all medical laboratory testing, there is a small chance that the laboratory could report inaccurate information. For example, the laboratory could report that a given genotype is present when in fact it is not. Any kind of laboratory error may lead to incorrect decisions regarding medical treatment and/or diet and fitness recommendations. If a laboratory error has occurred or is suspected, a health care professional may wish to pursue further evaluation and/or other testing. Further testing may be pursued to verify any results for any reason. Limitations The purpose of this test is to provide information about how a tested individual s genes may affect carrier status for some inherited diseases, responses to some drugs, risk for specific common health conditions, and/or selected diet, nutrition and/or exercise responses, as well as to learn more about the tested individual s ancient ancestry, depending upon the specific genetic testing that is ordered by the health care professional. Tested individuals should not make any changes to any medical care (including but not limited to changes to dosage or frequency of medications, diet and exercise regimens, or pregnancy planning) based on genetic testing results without consulting a health care professional. The science behind the significance or interpretation of certain testing results continues to evolve. Although great strides have been made to advance the potential usefulness of genetic testing, there is still much to be discovered. Genetic testing is based upon information, developments and testing techniques that are known today. Future research may reveal changes in the interpretation of previously obtained genetic testing results. For example, any genetic test is limited by the variants being tested. The interpretation of the significance of some variants may change as more research is done about them. Some variants that are associated with disease, drug response, or diet, nutrition and exercise response may not be tested; possibly these variants have not yet been identified in genetic studies. any of the conditions and drug responses that are tested are dependent on genetic factors as well as nongenetic factors such as age, personal health and family health history, diet, and ethnicity. As such, an individual may not exhibit the specific drug response, disease, or diet, nutrition and exercise response consistent with the genetic test results. Another limitation for some conditions, particularly in the areas of diet and exercise, is that genetic associations have been studied and observed in Caucasian populations only, and in some cases only in one gender. In this case, the interpretations and recommendations are made in the context of Caucasian studies, but the results may or may not be relevant to tested individuals who are of non-caucasian or mixed ethnicities or the non-studied gender. If patient ethnicity is not disclosed in the test requisition form the ethnicity field in the report will read as "Ethnicity: Not Reported". Such reports will be defaulted to phenotype list displayed for Caucasian ethnicity. Based on test results and other medical knowledge of the tested individual, health care professionals might consider additional independent testing, or consult another health care professional or genetic counselor. Laboratory Director: Nilesh Dharajiya,.D. CLIA Number: 05D Nexus Center Drive, San Diego, CA PAGE 10 of 11

11 ENTAL HEALTH DNA INSIGHT RESULT STATUS DEFINITIONS Amended Test results and/or patient information that have been revised in a way that does not impact the clinical significance of the result(s) and/or patient diagnosis, treatment or management. Corrected Test results and/or patient information that have been revised in a way that may impact the clinical significance of the result(s) and/or patient diagnosis, treatment or management. Final Test results that are available at the time of report issue or have been revised from pending status to final status. Pending Test results that are not available at the time of report issue. All pending results will be specified in the report. Laboratory Director: Nilesh Dharajiya,.D. CLIA Number: 05D Nexus Center Drive, San Diego, CA PAGE 11 of 11

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