Mental Health DNA Insight®
Help Predict a Patient’s Response to Medications
CYP2D6, CYP3A4, SLC6A4, CYP2C19, HTR2A
Selective serotonin reuptake inhibitors (SSRIs) are prescribed to treat various psychiatric conditions, including depression, anxiety and personality disorders. SSRIs act by blocking the serotonin (5-HT) receptors in the brain1. Suboptimal responses can delay the use of effective medications and remission of symptoms2. Genetic differences can play an important role in determining patient responses3.
CYP2D6, CYP3A4, CYP2B6, SLC6A4
Serotonin and norepinephrine reuptake inhibitors (SNRIs) such as duloxetine, levomilnacipran and venlafaxine are primarily indicated for the treatment of major depressive disorder (MDD)4-7. Some SNRIs are also prescribed to treat anxiety disorders and neuropathic pain. SNRIs, like SSRIs, are second-generation antidepressants that are better tolerated than first-generation antidepressants such as tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs)8.
Tricyclic antidepressants (TCAs) are prescribed to treat depression and various other psychiatric conditions9. TCAs act by blocking the neuronal uptake of norepinephrine and serotonin10; the binding of TCAs to cholinergic, alpha-adrenergic, serotonin and histamine receptors contributes to various side effects.
CYP2D6, CYP3A4, CYP2B6, SLC6A4
Other antidepressants that are used to treat depression and anxiety disorders include: Bupropion - a norepinephrine and dopamine reuptake inhibitor (NDRI) and a non-competitive antagonist of the nicotine receptors11, 12; Buspirone – an anti-anxiety medication unrelated to benzodiazepines13; Mirtazapine - a commonly prescribed second-generation tetracyclic antidepressant that inhibits adrenergic alpha2-autoreceptors and serotonin 5-HT2 and 5-HT3 receptors14, 15; nefazodone - a phenylpiperazine antidepressant not related to SSRIs, TCAs and monoamine oxidase inhibitors, and blocks the serotonin 5-HT2 receptors16, 17; trazodone - a serotonin antagonist and a serotonin reuptake inhibitor (SARI) related to nefazodone18, 19; vortioxetine - a multimodal antidepressant that can be a useful alternative to serotonergic antidepressants for some patients who are partial responders or non-responders20, 21.
Atomoxetine is indicated for the treatment of attention deficit/hyperactivity disorder (ADHD) among children, adolescents and adults. It is a potent and selective inhibitor of the pre-synaptic norepinephrine transporter with minor affinity for serotonin and dopamine transporters29.
Benzodiazepines (BDZ) are a class of drugs primarily used for treating seizures, but they also are effective in treating epilepsy, panic disorders and various other disorders30. The exact mechanism of action of BDZs is not known, but they appear to work by affecting neurotransmitters like gamma-aminobutryic acid (GABA) in the brain.
HLA-A, HLA-B, UGT1A4, POLG, CYP2C9
Carbamazepine, divalproex, lamotrigine, oxcarbazepine, phenytoin and valproic acid are used to treat epilepsy, mania/bipolar disorder and neuropathic pain31-36. The most serious side effects associated with carbamazepine, lamotrigine, oxcarbazepine and phenytoin are blistering skin reactions known as Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis19 37, 38. Other mood stabilizers such as valproic acid and divalproex can increase the risk of liver damage and resultant death in patients with hereditary neurometabolic disorder caused due to inherited POLG mutations35, 39-41.
CYP2D6, CYP1A2, HTR2C, DRD2
Typical antipsychotics (TAPs), also known as first generation antipsychotics, are prescribed to treat various psychiatric disorders, including schizophrenia, mania, agitated behavior and severe anxiety42, 43. This class of drugs acts by blocking dopamine D1 and D2 receptors44-47.
Atypical antipsychotics are prescribed to treat various psychiatric disorders, including schizophrenia, schizoaffective disorder and bipolar mania48, 49. These medications bind serotonin and dopamine receptors50-55. Stimulation of serotonin receptor 2C (5-HT2C, 5-HTR2C, HTR1C) results in secretion of pro-opiomelanocortin (POMC), enhanced satiety and decreased food intake; therefore, serotonergic agents can decrease food intake and promote weight loss56, 57. Indeed, one of the major side-effects associated with atypical antipsychotics is significant weight gain57.
Dextromethorphan and quinidine sulfate combination is an oral formulation used to treat pseudo bulbar effect. Galantamine is a cholinesterase inhibitor indicated for the treatment of mild to moderate Alzheimer’s disease22-25. Modafinil is a wakefulness-promoting agent used to treat excessive daytime sleepiness associated with narcolepsy26. Modafinil is often used in combination with tricyclic antidepressant medication27. Tetrabenazine is a vesicular monoamine transporter 2 (VMAT) inhibitor indicated for the treatment of chorea associated with Huntington’s disease28.
Mental Health DNA Insight® can be ordered from a licensed and registered physician or other qualified healthcare provider.
The patient will provide a saliva or blood sample using the collection kit in the Pathway Genomics box.
The authorized physician will mail the sample back to Pathway Genomics, along with the test requisition and consent form (return shipping provided). View the saliva collection instructional video here. For blood collection instructions, click here.
Pathway Genomics processes and analyzes the submitted sample in its CLIA certified and CAP accredited laboratory. Typically within two to three weeks, the patient’s personalized results will be available to the ordering physician. The results will then be released to the patient. Pathway Genomics has a team of genetic counselors available to ensure that both the patient and the physician understand the information in the report, and to answer additional questions. To contact a Pathway Genomics genetic counselor, please call client services department at 877-505-7374 or email firstname.lastname@example.org.
Mental Health DNA Insight® is best suited for individuals who are about to start one of the indicated psychiatric medications, as well as for patients who are currently taking these medications but are not getting the optimal therapeutic response or are experiencing side effects. This clinically-actionable genetic test can help physicians guide patients’ prescriptions, adjust dosages, and avoid or monitor medications that may have potential adverse effects.