Methods for selecting medications for treating patients having attention-deficit hyperactivity disorder

Abstract

Methods for selecting a medication for a patient are described that include determining the patient's genotype for a panel of genes, identifying a phenotype associated with the genotype for each gene, and selecting the medication based on the phenotype.

1 - 27 . (canceled) 
     
     
         28 . A non-transitory computer-readable medium containing executable instructions that when executed causes a processor to perform operations for selecting a medication for a patient having ADHD, comprising (a) receiving, in a computer system, the patient's genotype for a set of markers for a panel of genes wherein the set of markers and genes comprises the following: (i) one or more cytochrome P450 CYP2D6 alleles selected from the group consisting of *2BD, *3, *4, *5, *6, *7, *8, *9, *10, *11, *12, *15, *17, and *41; (ii) the tandem duplication polymorphism in the promoter region of the dopamine receptor DRD4 gene that consists of a 120 base pair allele and a 240 base pair allele; (iii) the G1278A polymorphism in exon 9 of the norepinephrine transporter gene SLC6A2; (iv) the 10 repeat unit and the 9 repeat unit of the variable number tandem repeat (VNTR) polymorphism in the dopamine transporter gene SLC6A3; and (v) the G158A polymorphism in the catechol-0-methyl transferase gene COMT; (b) assigning a phenotype for each gene based on the patient's genotype as follows: a CYP2D6 phenotype selected from phenotype 1, phenotype 2, and phenotype 3, wherein a homozygous or compound heterozygous genotype for any of the alleles in (i) is assigned phenotype 1, a heterozygous genotype for any of the alleles in (i) is assigned phenotype 2, and a genotype lacking any of the alleles in (i) is assigned phenotype 3; a DRD4 phenotype selected from a positive phenotype if the genotype is homozygous for the rare 120 allele and a negative phenotype if the common 240 allele is present; a SLC6A3 phenotype selected from a positive phenotype if the genotype is homozygous for the 10 repeat unit and a negative phenotype if the 9 repeat unit is present; a SLC6A2 phenotype selected from a positive phenotype if the genotype is G/A or G/G and a negative phenotype if the genotype is A/A; a COMT phenotype selected from an active phenotype if the genotype is val/val and a less active phenotype if the genotype is val/met or met/met; (c) combining, using said computer system, each assigned phenotype for each gene of the panel of genes into a combined phenotype for the patient; (d) applying a set of rules to select a medication for the patient based upon the patient's combined phenotype; (e) outputting the selection of medication according to the patient's combined phenotype as follows: the patient has a combined phenotype selected from:
 (i) DRD4 negative phenotype; SLC6A3 negative phenotype; SLC6A2 negative phenotype; COMT active phenotype; CYP2D6 phenotype 2;   (ii) DRD4 negative phenotype; SLC6A3 negative phenotype; SLC6A2 negative phenotype; COMT active phenotype; CYP2D6 phenotype 3;   (iii) DRD4 negative phenotype; SLC6A3 negative phenotype; SLC6A2 positive phenotype; COMT less active phenotype; CYP2D6 phenotype 2;   (iv) DRD4 negative phenotype; SLC6A3 positive phenotype; SLC6A2 negative phenotype; COMT less active phenotype; CYP2D6 phenotype 2;   (v) DRD4 positive phenotype; SLC6A3 negative phenotype; SLC6A2 negative phenotype; COMT less active phenotype; CYP2D6 phenotype 2;   (vi) DRD4 negative phenotype; SLC6A3 negative phenotype; SLC6A2 negative phenotype; COMT less active phenotype; CYP2D6 phenotype 2;   (vii) DRD4 negative phenotype; SLC6A3 positive phenotype; SLC6A2 positive phenotype; COMT less active phenotype; CYP2D6 phenotype 3;   (viii) DRD4 positive phenotype; SLC6A3 negative phenotype; SLC6A2 positive phenotype; COMT less active phenotype; CYP2D6 phenotype 3;   (ix) DRD4 negative phenotype; SLC6A3 negative phenotype; SLC6A2 positive phenotype; COMT less active phenotype; CYP2D6 phenotype 3:   (x) DRD4 positive phenotype; SLC6A3 positive phenotype; SLC6A2 negative phenotype; COMT less active phenotype; CYP2D6 phenotype 3;   (xi) DRD4 negative phenotype; SLC6A3 positive phenotype; SLC6A2 negative phenotype; COMT less active phenotype; CYP2D6 phenotype 3;   (xii) DRD4 positive phenotype; SLC6A3 negative phenotype; SLC6A2 negative phenotype; COMT less active phenotype; CYP2D6 phenotype 3;   (xiii) DRD4 negative phenotype; SLC6A3 negative phenotype; SLC6A2 negative phenotype; COMT less active phenotype; CYP2D6 phenotype 3; and the output is amphetamines or atomoxetine; or   the patient has a combined phenotype that is DRD4 negative phenotype; SLC6A3 negative phenotype; SLC6A2 negative phenotype; COMT less active phenotype; CYP2D6 phenotype 1; and the output is low dose atomoxetine.   
     
     
         29 . The method of  claim 28 , wherein the patient's genotype is received directly from equipment used in determining the patient's genotype. 
     
     
         30 . The method of  claim 28 , wherein a user enters the patient's genotype in the computer system. 
     
     
         31 . The method of  claim 28 , wherein said panel of genes further comprises at least two genes selected from the group comprising SNAP25, ADRA2A, SLCA1A, SL6A4, DRD1, DRD2, DRD3, DRD5, 5-HTTR, CES1, CRH, and TPH2.