METHOD AND SYSTEM TO PREDICT RESPONSE TO TREATMENTS FOR MENTAL DISORDERS
The present inventions relates to methods and assays to predict the response of an individual to psychiatric treatment and to a method to improve medical treatment of a disorder, which responsive to treatment with a psychiatric treatment.
1 . A method for predicting an individual's likely response to a medication for a mental disorder, comprising genotyping genetic variations in an individual to determine:
a categorical grade to an individual's likely ability to metabolize a particular psychiatric medication, a categorical grade for a psychiatric medication's potential efficacy with respect to the individual, and a categorical grade to the propensity for the individual to have a negative adverse reaction to the particular psychiatric medication;
aggregating the categorical grades; and thereafter identifying the least positive grade as the recommended prediction for the individual.
2 . The method of claim 1 , further comprising genotyping genetic variations in an individual to determine an individual's susceptibility to a mental disorder.
3 . The method of claim 1 , wherein the mental disorder is selected from mood disorders, psychotic disorders, personality disorders, anxiety disorders, substance-related disorders, childhood disorders, dementia, autistic disorder, adjustment disorder, delirium, multi-infarct dementia, eating disorders, addictive behaviors, ADHD, PTSD, and Tourette's disorder.
4 . The method of claim 1 , wherein a genetic variation in the individual will reassign one or more of the categorical grades from a default category of typical use to preferential use or precautionary use.
5 . The method of claim 1 , wherein a drug is prescribed to the individual with a recommendation of:
Use as directed
Preferential Use
Precautionary Use
6 . The method of claim 1 , wherein each categorical grade is assigned to the three or more categories below:
Use as Directed
Preferential Use
May Have Limitations or Significant Limitations
May Cause Serious Adverse Events.
7 . The method of claim 1 , wherein the medication is a psychiatric medication selected from antidepressants, antipsychotics, stimulants, anxiolytics, mood stabilizers, and depressants.
8 . The method of claim 1 , wherein the medications is selected from lamotrigine, Quetiapine, carbamazepine, aripiprazole, olanzapine, risperidone, ziprasidone, citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, mirtazapine, oxcarbazepine, clozapine, duloxetine, venlafaxine, amitriptyline, nortriptyline, imipramine, escitalopram, clomipramine, desipramine, doxepin, trimipramine, iloperidone, asenapine, lurasidone, paliperidone, haloperidol, perphenazine, thioridazine, lithium, zuclopenthixol, valproic acid, buspirone, gabapentin, topiramate, trazodone, chlorpromazine, fluphenazine, loxapine, thiothixene, trifluoperazine, bupropion, amphetamine, modafinil, phenytoin, droperidol, diazepam, nordazepam, temazepam, triazolam, flurazepam, bromazepam, clobazam, etizolam, alprazolam, lorazepam, midazolam, oxazepam, clonazepam, and protriptyline.
9 . The method of claim 1 , wherein said method comprises genotyping a panel of at least one gene that affects the rate of drug metabolism, a panel of genes that affect a medication's potential efficacy with respect to the individual, and a panel of genes that affect the propensity for the individual to have a negative adverse reaction to a particular medication.
10 . The method of claim 1 , wherein the panel for affecting drug metabolism comprises at least one gene that affects biochemical modification of pharmaceutical substances or xenobiotics, the panel for affecting efficacy comprises at least one neurotransmitter modulating gene and the panel for affecting adverse effect comprises at least one gene for undesired effects, e.g., side effects, that can be categorized as 1) mechanism based reactions and 2) idiosyncratic, “unpredictable” effects apparently unrelated to the primary pharmacologic action of the compound.
11 . The method of claim 1 , wherein the panel of genes for affecting metabolism is at least one cytochrome P450 gene,
12 . The method of claim 1 , wherein the panel for genes for affecting metabolism is at least two cytochrome P450 genes.
13 . The method of claim 1 , wherein the panel for genes for affecting metabolism further comprises at least one gene selected from UDP-glucuronosyltransferase, 5,10-methylenetetrahydrofolate reductase, and ATP-binding cassette (ABC) transporters.
14 . The method of claim 1 , wherein the panel of genes for affecting metabolism is at least one gene selected from CYP1A1, CYP2A6, CYP2C9, CYP2D6, CYP2E1, CYP3A5, CYP1A2, CYP1B1, CYP2B6, CYP2C8, CYP2C18, CYP2C19, CYP2E1, CYP3A4, CYP3A5, UGT1A4, UGT1A1, UGT1A9, UGT2B4, UGT2B7, UGT2B 15, NAT1, NAT2, EPHX1, MTHFR, and ABCB1.
15 . The method of claim 1 , wherein the panel of genes for affecting efficacy is at least one gene for a serotonin transporter or receptor gene.
16 . The of claim 1 , wherein the panel of genes for affecting efficacy is a serotonin transporter and a serotonin receptor gene.
17 . The of claim 1 , wherein the panel of genes further comprises a dopamine transporter gene.
18 . The method of claim 1 , wherein the panel further comprises one or more dopamine receptor genes.
19 . The method of claim 1 , wherein said dopamine receptor genes encode dopamine receptors D1, D2, D3, D4 and D5.
20 . The method of claim 1 , wherein the panel of genes for affecting drug metabolism is CYP2D6, CYP2B6, CYP2C19, and UGT1A4 genes;
wherein the panel of genes for affecting efficacy is the serotonin transporter gene (SLC6A4), the serotonin receptor 2A gene (HTR2A) and dopamine receptor D2 (DRD2); and
wherein the panel of genes for affecting adverse reactions is the serotonin receptor 2A (HTR2A), the serotonin gene 2C (HTR2C) and the major histocompatibility complex, class I, B (HLA-B).
21 .- 38 . (canceled)