Methods for selecting medications

Abstract

The invention provides computer assisted methods for selecting an antidepressant medication for a patient. The methods utilize a combination genotype comprising at least three genes to guide medication selection.

1 - 47 . (canceled) 
     
     
         48 . A processor programmed to perform operations comprising:
 receiving a patient's genotype for a panel of at least three genes comprising cytochrome P450 gene CYP2D6, cytochrome P450 gene CYP2C19 and serotonin transporter gene 5HTTR, wherein
 (a) the cytochrome P450 CYP2D6 alleles comprise one or more of the fully functional alleles *1A, *2N, and *35, the partially functional allele *10, and non-functional alleles *3, *4, *5, *6, *7, *8, and *12, 
 (b) the cytochrome P450 CYP2Cl 9 alleles comprise one or 40 more of the fully functional alleles *1A and *1B, and non-functional alleles *2A, *2B, *3, *4, *SA, *SB, *6, *7 and *8, and 
 (c) the patient's genotype at the serotonin transporter gene 5HTTR is determined at the two alleles consisting of the short (s) and long (l) forms of the 5HTTR gene, wherein the long form of the 5HTTR gene comprises a 44 base pair insertion in the promoter region, and the short form of the 5HTTR gene comprises a 44 base pair deletion in the promoter region; 
   assigning a metabolic phenotype to each genotype of each cytochrome P450 gene, wherein the metabolic phenotype is assigned according to the number of functional, partially functional, or nonfunctional cytochrome P450 alleles in the genotype, the phenotypes comprising poor (P), intermediate (I), and extensive (E), and a phenotype of poor (P) comprising individuals who are homozygous or compound heterozygous for a partially functional or non-functional cytochrome P450 allele, a phenotype of intermediate (I) comprising individuals who are heterozygous, and a phenotype of extensive (E) comprising individuals who do not have any inactivating polymorphisms, deletions, or duplications among their cytochrome P450 alleles;   outputting a psychotropic medication based upon the patient's cytochrome P450 genotype and 5HTTR genotype.   
     
     
         49 . The processor of  claim 48 , wherein the medication is selected from the group consisting of
 (1) bupropion, mirtazapine, fluvoxamine and sertraline if the patient's metabolic phenotype is P/P (poor for both 2D6 and 2C19) and the 5HTTR genotype is heterozygous (1/s) or homozygous (1/1);   (2) bupropion, mirtazapine and fluvoxamine if the patient's metabolic phenotype is P/P and the 5HTTR genotype is homozygous (s/s);   (3) bupropion, mirtazapine, fluvoxamine, sertraline, amitriptyline, nortriptyline, venlafaxine and paroxetine if the patient's metabolic phenotype is I/P (intermediate for 2D6 and poor for 2Cl 9) and the 5HTTR genotype is heterozygous (1/s) or homozygous (1/1);   (4) bupropion, mirtazapine, fluvoxamine, sertraline, amitriptyline, nortriptyline and venlafaxine, if the patient's metabolic phenotype is I/P and the 5HTTR genotype is homozygous (s/s);   (5) bupropion, mirtazapine, citalopram, escitalopram, fluvoxamine and sertraline if the patient's metabolic phenotype is P/E (poor for 2D6 and extensive for 2C19) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);   (6) bupropion, mirtazapine, citalopram, escitalopram, and fluvoxamine if the patient's metabolic phenotype is P/E and the 5HTTR genotype is homozygous (s/s);   (7) bupropion, venlafaxine, amitriptyline, imipramine, mirtazapine, nortriptyline, fluoxetine, paroxetine, sertraline, citalopram, escitalopram and fluvoxamine if the   
       patient's metabolic phenotype is E/P (extensive for 2D6 and poor for 2C19), and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);
 (8) bupropion, venlafaxine, amitriptyline, imipramine, mirtazapine, nortriptyline, fluoxetine, paroxetine and sertraline if the patient's metabolic phenotype is E/P and the 5HTTR genotype is homozygous (s/s); 
 (9) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline, venlafaxine, citalopram, fluvoxamine, fluoxetine and paroxetine, if the patient's metabolic phenotype is I/E (intermediate for 2D6 and extensive for 2C19) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l); 
 (10) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline, venlafaxine, citalopram and fluvoxamine, if the patient's metabolic phenotype is I/E and the 5HTTR genotype is homozygous (s/s); and 
 (11) amitriptyline, bupropion, citalopram, fluvoxamine, imipramine, mirtazapine, nortriptyline, venlafaxine, escitalopram, fluoxetine, paroxetine and sertraline if the patient's metabolic phenotype is E/E (extensive for both 2D6 and 2C19) and the 5HTTR genotype is heterozygous (l/s) or homozygous (s/s or l/l). 
 
     
     
         50 . The processor of  claim 49 , wherein said panel further comprises at least one additional gene selected from the group of genes comprising CYP3A4, CYP1A1, a dopamine transporter gene, a serotine receptor gene, dopamine receptor D1, dopamine receptor D2, dopamine receptor D3, dopamine receptor D4, dopamine receptor D5, dopamine receptor D6, serotonin receptor 1A, serotonin receptor 1B, serotonin receptor 1D, serotonin receptor 2A, serotonin receptor 2C, catechoyl-O-methyl transferase gene, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2E1, CYP3A5, a tryptophan hydroxylase gene, DATl, and TPH gene. 
     
     
         51 . The processor of  claim 49 , wherein said panel further comprises at least two additional genes selected from the group of genes comprising CYP3A4, CYPlAl, a dopamine transporter gene, a serotine receptor gene, dopamine receptor D1, dopamine receptor D2, dopamine receptor D3, dopamine receptor D4, dopamine receptor D5, dopamine receptor D6, serotonin receptor lA, serotonin receptor lB, serotonin receptor 1D, serotonin receptor 2A, serotonin receptor 2C, catechoyl-O-methyl transferase gene, CYPlBl, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2El, CYP3A5, 5HTTR, a tryptophan hydroxylase gene, DATl, and TPH gene. 
     
     
         52 . The processor of  claim 48 , wherein said psychotropic medication is selected from the group of psychotropic medications comprising an antipsychotic agent, an antianxiety-sedative agent, a mood-stabilizing agent, an anti-depressant, clonazepam, trazodone, lamotrigine, oxycarbazepine, aripiprazole, bupropion, mirtazapine, fluvoxamine, sertraline, amitriptyline, nortriptyline, venlafaxine, paroxetine, citalopram, escitalopram, and imipramine. 
     
     
         53 . The processor of  claim 49 , wherein said patient is in need of an anti-anxiety sedative agent and wherein said panel further comprises at least one additional gene selected from the group of genes comprising serotonin receptor lA, serotonin receptor lB, serotonin receptor 1D, serotonin receptor 2A, serotonin receptor 2C, 5HTTR, and serotonin transporter gene. 
     
     
         54 . The processor of  claim 49 , wherein said patient is in need of a mood stabilizing agent and wherein said panel further comprises at least one additional gene selected from the group of genes comprising 5HTTR, HTR2A, serotonin transporter, and CYP3A4. 
     
     
         55 . The processor of  claim 49 , wherein said patient is in need of an antipsychotic agent and wherein said panel further comprises a dopamine transporter gene. 
     
     
         56 . The processor of  claim 49 , wherein said patient is in need of an anti-depressant and wherein said panel further comprises at least one additional gene selected from the group comprising a serotonin transporter gene, a serotonin receptor gene, a serotonin receptor 2A gene, CYP3A4, 5HTTR, and HTR2A. 
     
     
         57 . The processor of  claim 48 , wherein said psychotropic medication is selected from the group of psychotropic medications comprising an antipsychotic agent, an antianxiety-sedative agent, a mood-stabilizing agent an anti-depressant, clonazepam, trazodone, lamotrigine, oxycarbazepine, aripiprazole, bupropion, mirtazapine, fluvoxamine, sertraline, amitriptyline, nortriptyline, venlafaxine, paroxetine, citalopram, escitalopram, and imipramine.