Methods for selecting medications

• US 8,401,801 B2
• Filed: 02/20/2004
• Issued: 03/19/2013
• Est. Priority Date: 02/20/2003
• Status: Active Grant

• Current Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Original Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Inventors: Mrazek, David A., O'Kane, Dennis J., Black, John L.
• Primary Examiner(s): Harward, Soren
• Application Number:
  US10/545,931
• Publication Number:
  US 20070003931A1
• Time in Patent Office: 3,315 Days
• Field of Search: None
• US Class Current: 702/20
• CPC Class Codes: C12Q 1/6827 for detection of mutation or polymorphism
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/172 Haplotypes
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16B 50/00 ICT programming tools or database systems specially adapted for bioinformatics
• CPC Class Codes: G16B 50/10 Ontologies; Annotations
• CPC Class Codes: G16H 10/60 for patient-specific data, e.g. for electronic patient records
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment

Abstract

Methods for selecting a medication for a patient are described that include determining the patient'"'"'s genotype for a panel of genes and selecting the medication based on the genotype. Articles of manufacture also are provided that include nucleic acid molecules for detecting alleles of genes encoding drug metabolizing enzymes and genes encoding products involved in neurotransmission.

Claims

1. A method of administering an antidepressant medication to a patient in need thereof comprising:

(1) determining the patients genotype for a panel of genes comprising the following;

(a) a cytochrome P450 CYP2D6 gene consisting of two alleles independently selected from the group consisting of fully functional alleles 2D6*1A, *2, *2N, and *35, partially functional alleles 2D6*10 and *17, and non-functional alleles 2D6*3, *4, *5, *6, *7, *8, and *12,

(b) a cytochrome P450 CYP2C19 gene consisting of two alleles independently selected from the group consisting of fully functional alleles 2C19*1A and *1B, and non-functional alleles 2C19*2A, *2B, *3, *4, *5A, *5B, *6, *7 and *8, and

(c) a serotonin transporter gene 5HTTR consisting of two alleles independently selected from the short (s) and long (1) forms of the 5HTTR gene;

(2) assigning a metabolic phenotype to the patient based on the genotype of the cytochrome P450 genes in (1), wherein the metabolic phenotype is selected from poor (P), intermediate (I), and extensive (E), and said phenotype is assigned based upon the number of functional alleles for each cytochrome P450 gene as follows;

P=no fully functional alleles and either one or no partially functional alleles, I=either one fully functional allele and a non-functional allele or two partially functional alleles, and E=either one fully functional allele and one partially functional allele or two fully functional alleles; and

(3) administering to the patient an antidepressant medication selected from the group consisting of;

(i) 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 (l/s) or homozygous (l/l);

(ii) bupropion, mirtazapine and fluvoxamine if the patient'"'"'s metabolic phenotype is P/P and the 5HTTR genotype is homozygous (s/s);

(iii) bupropion, mirtazapine, fluvoxamine, sertraline, amitriptyline, nortriptyline, venlafaxine and paroxetine if the patient'"'"'s metabolic phenotype is I/P (intermediate for 2D6 and poor for 2C19) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(iv) 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);

(v) 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);

(vi) bupropion, mirtazapine, citalopram, escitalopram, and fluvoxamine if the patient'"'"'s metabolic phenotype is P/E and the 5HTTR genotype is homozygous (s/s);

(vii) 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);

(viii) 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);

(ix) 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);

(x) 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

(xi) 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).

3. The method of claim 1 or 2, wherein the method further comprises receiving, in a computer system, the patients genotype for the panel of genes, said computer system comprising a database, wherein said database comprises a plurality of antidepressant medication profiles.

4. The method of claim 3, wherein one or more of steps 1 and 2 are performed using said computer system and the method further comprises a step of outputting the identity of the antidepressant medication for administering to the patient from the computer system.

5. The method of claim 3, wherein a user enters the patient'"'"'s genotype in the computer system.

6. The method of claim 4, wherein the patient'"'"'s genotype is received directly from equipment used in determining the patient'"'"'s genotype.

2. A method of administering an antidepressant medication to a patient in need thereof comprising:

(1) determining the patients genotype for following panel of genes;

(a) a cytochrome P450 CYP3A4 gene consisting of two alleles independently selected from the group consisting of fully functional alleles 3A4*1A, *1B, *2, *5, *6, and *15A, partially functional alleles 3A4*12, *13 and *17, and increased functional alleles 3A4*18A,

(b) a cytochrome P450 CYP1A2 gene consisting of two alleles independently selected from the group consisting of fully functional alleles 1A2*1A, partially functional alleles 1A2*3, and increased functional alleles 1A2*1F, and

(c) a cytochrome P450 CYP2D6 gene consisting of two alleles independently selected from the group consisting of fully functional alleles 2D6*1A, *2, *2N, and *35, partially functional alleles 2D6*10 and *17, and non-functional alleles 2D6*3, *4, *5, *6, *7, *8, and *12,

(d) a cytochrome P450 CYP2C19 gene consisting of two alleles independently selected from the group consisting of fully functional alleles 2C19*1A and *1B, and non-functional alleles 2C19*2A, *2B, *3, *4, *5A, *5B, *6, *7 and *8, and

(e) a serotonin transporter gene 5HTTR consisting of two alleles independently selected from the short (s) and long (l) forms of the 5HTTR gene;

(f) a serotonin receptor gene HTR2A T102C polymorphism consisting of two alleles independently selected from the normal (T) and mutant (C) forms of the HTR2A gene;

(2) assigning a metabolic phenotype to the patient based on the genotype of the cytochrome P450 genes in (1), wherein the metabolic phenotype is selected from poor (P), intermediate (I), and extensive (E), and said phenotype is assigned based upon the number of functional alleles for each cytochrome P450 gene as follows;

P=either two partially functional alleles or two increased functional alleles, I=either one fully functional allele and a partially functional allele or one fully functional allele and an increased functional allele, and E=either one partially functional allele and one increased functional allele or two fully functional alleles; and

(3) administering to the patient an antidepressant medication selected from the group consisting of;

(i) bupropion, mirtazapine, fluvoxamine and sertraline if the patient'"'"'s metabolic phenotype is P/P (poor for both 2D6 and 2C19), P, I or E for 3A4, I or E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(ii) bupropion, mirtazapine, and sertraline if the patient'"'"'s metabolic phenotype is P/P for 2D6 and 2C19, P, I or E for 3A4, P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(iii) bupropion, mirtazapine and fluvoxamine if the patient'"'"'s metabolic phenotype is P/P for 2D6 and 2C19, P, I or E for 3A4, E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is homozygous (s/s);

(iv) bupropion and mirtazapine if the patient'"'"'s metabolic phenotype is P/P for 2D6 and 2C19, P, I or E for 3A4, I or P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is homozygous (s/s);

(v) bupropion, mirtazapine, fluvoxamine, sertraline, amitriptyline, nortriptyline, venlafaxine and paroxetine if the patient'"'"'s metabolic phenotype is I/P (intermediate for 2D6 and poor for 2C19), E for 3A4, I or E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(vi) bupropion, mirtazapine, sertraline, amitriptyline, nortriptyline, venlafaxine and paroxetine if the patient'"'"'s metabolic phenotype is I/P for 2D6 and 2C19, E for 3A4, P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(vii) bupropion, mirtazapine, fluvoxamine, sertraline, amitriptyline, nortriptyline, and paroxetine if the patient'"'"'s metabolic phenotype is I/P for 2D6 and 2C19, I or P for 3A4, I or E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(viii) bupropion, mirtazapine, fluvoxamine, sertraline, amitriptyline, nortriptyline, and venlafaxine if the patient'"'"'s metabolic phenotype is I/P for 2D6 and 2C19, E for 3A4, I or E for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(ix) bupropion, mirtazapine, sertraline, amitriptyline, nortriptyline and paroxetine if the patient'"'"'s metabolic phenotype is I/P for 2D6 and 2C19, I or P for 3A4, P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(x) bupropion, mirtazapine, sertraline, amitriptyline, nortriptyline, and venlafaxine if the patient'"'"'s metabolic phenotype is I/P for 2D6 and 2C19, E for 3A4, P for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xi) bupropion, mirtazapine, fluvoxamine, sertraline, amitriptyline and nortriptyline if the patient'"'"'s metabolic phenotype is I/P for 2D6 and 2C19, I or P for 3A4, I or E for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xii) bupropion, mirtazapine, sertraline, amitriptyline and nortriptyline if the patient'"'"'s metabolic phenotype is I/P for 2D6 and 2C19, I or P for 3A4, P for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xiii) bupropion, mirtazapine, fluvoxamine, sertraline, amitriptyline, nortriptyline and venlafaxine if the patient'"'"'s metabolic phenotype is I/P for 2D6 and 2C19, E for 3A4, E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is homozygous (s/s);

(xiv) bupropion, mirtazapine, sertraline, amitriptyline, nortriptyline and venlafaxine if the patient'"'"'s metabolic phenotype is I/P for 2D6 and 2C19, E for 3A4, I or P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is homozygous (s/s);

(xv) bupropion, mirtazapine, fluvoxamine, sertraline, amitriptyline and nortriptyline if the patient'"'"'s metabolic phenotype is I/P for 2D6 and 2C19, I or P for 3A4, E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is homozygous (s/s);

(xvi) bupropion, mirtazapine, sertraline, amitriptyline and nortriptyline if the patient'"'"'s metabolic phenotype is I/P for 2D6 and 2C19, I or P for 3A4, I or P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is homozygous (s/s);

(xvii) bupropion, mirtazapine, citalopram, escitalopram, fluvoxamine and sertraline if the patient'"'"'s metabolic phenotype is P/E (poor for 2D6 and extensive for 2C19), E, I or P for 3A4, E or I for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xviii) bupropion, mirtazapine, citalopram, escitalopram and sertraline if the patient'"'"'s metabolic phenotype is P/E for 2D6 and 2C19, E, I or P for 3A4, P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xix) bupropion, mirtazapine, citalopram, escitalopram, and fluvoxamine if the patient'"'"'s metabolic phenotype is P/E for 2D6 and 2C19, E, I or P for 3A4, E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is homozygous (s/s);

(xx) bupropion, mirtazapine, citalopram and escitalopram if the patient'"'"'s metabolic phenotype is P/E for 2D6 and 2C19, E, I or P for 3A4, I or P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is homozygous (s/s);

(xxi) 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), E or I for 3A4, E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xxii) bupropion, amitriptyline, imipramine, mirtazapine, nortriptyline, fluoxetine, paroxetine, sertraline, citalopram, escitalopram and fluvoxamine if the patient'"'"'s metabolic phenotype is E/P for 2D6 and 2C19, P for 3A4, E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xxiii) bupropion, venlafaxine, amitriptyline, imipramine, mirtazapine, nortriptyline, fluoxetine, paroxetine, sertraline, citalopram and escitalopram if the patient'"'"'s metabolic phenotype is E/P for 2D6 and 2C19, E or I for 3A4, I or P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xxiv) bupropion, amitriptyline, imipramine, mirtazapine, nortriptyline, fluoxetine, paroxetine, sertraline, citalopram and escitalopram if the patient'"'"'s metabolic phenotype is E/P for 2D6 and 2C19, P for 3A4, I or P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xxv) bupropion, venlafaxine, amitriptyline, imipramine, mirtazapine, nortriptyline, fluoxetine, paroxetine and sertraline if the patient'"'"'s metabolic phenotype is E/P for 2D6 and 2C19, E or I for 3A4, E, I or P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is homozygous (s/s);

(xxvi) bupropion, amitriptyline, imipramine, mirtazapine, nortriptyline, fluoxetine, paroxetine and sertraline if the patient'"'"'s metabolic phenotype is E/P for 2D6 and 2C19, P for 3A4, E, I or P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is homozygous (s/s);

(xxvii) bupropion, venlafaxine, amitriptyline, imipramine, mirtazapine, nortriptyline, fluoxetine and sertraline if the patient'"'"'s metabolic phenotype is E/P for 2D6 and 2C19, E or I for 3A4, E, I or P for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is homozygous (s/s);

(xxviii) bupropion, amitriptyline, imipramine, mirtazapine, nortriptyline, fluoxetine and sertraline if the patient'"'"'s metabolic phenotype is E/P for 2D6 and 2C19, P for 3A4, E, I or P for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is homozygous (s/s);

(xxix) 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), E for 3A4, E or I for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xxx) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline, citalopram, fluvoxamine, fluoxetine and paroxetine if the patient'"'"'s metabolic phenotype is I/E for 2D6 and 2C19, I or P for 3A4, E or I for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xxxi) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline, venlafaxine, citalopram, fluoxetine and paroxetine if the patient'"'"'s metabolic phenotype is I/E for 2D6 and 2C19, E for 3A4, P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xxxii) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline, venlafaxine, citalopram, fluvoxamine and fluoxetine if the patient'"'"'s metabolic phenotype is I/E for 2D6 and 2C19, E for 3A4, E or I for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xxxiii) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline, citalopram, fluoxetine and paroxetine, if the patient'"'"'s metabolic phenotype is I/E for 2D6 and 2C19, I or P for 3A4, P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xxxiv) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline, citalopram, fluvoxamine and fluoxetine if the patient'"'"'s metabolic phenotype is I/E for 2D6 and 2C19, I or P for 3A4, E or I for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xxxv) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline, venlafaxine, citalopram and fluoxetine if the patient'"'"'s metabolic phenotype is I/E for 2D6 and 2C19, E for 3A4, P for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xxxvi) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline, citalopram and fluoxetine if the patient'"'"'s metabolic phenotype is I/E for 2D6 and 2C19, I or P for 3A4, P for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xxxvii) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline, venlafaxine, citalopram and fluvoxamine if the patient'"'"'s metabolic phenotype is I/E for 2D6 and 2C19, E for 3A4, E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is homozygous (s/s);

(xxxviii) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline, citalopram and fluvoxamine if the patient'"'"'s metabolic phenotype is I/E for 2D6 and 2C19, I or P for 3A4, E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is homozygous (s/s);

(xxxix) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline, venlafaxine and citalopram if the patient'"'"'s metabolic phenotype is I/E for 2D6 and 2C19, E for 3A4, I or P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is homozygous (s/s);

(xl) bupropion, mirtazapine, escitalopram, sertraline, amitriptyline, imipramine, nortriptyline and citalopram if the patient'"'"'s metabolic phenotype is I/E for 2D6 and 2C19, I or P for 3A4, I or P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is homozygous (s/s);

(xli) 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), E or I for 3A4, E or I for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xlii) amitriptyline, bupropion, citalopram, fluvoxamine, imipramine, mirtazapine, nortriptyline, escitalopram, fluoxetine, paroxetine and sertraline if the patient'"'"'s metabolic phenotype is E/E for 2D6 and 2C19, P for 3A4, E or I for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xliii) amitriptyline, bupropion, citalopram, imipramine, mirtazapine, nortriptyline, venlafaxine, escitalopram, fluoxetine, paroxetine and sertraline if the patient'"'"'s metabolic phenotype is E/E for 2D6 and 2C19, E or I for 3A4, P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xliv) amitriptyline, bupropion, citalopram, imipramine, mirtazapine, nortriptyline, escitalopram, fluoxetine, paroxetine and sertraline if the patient'"'"'s metabolic phenotype is E/E for 2D6 and 2C19, P for 3A4, P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T or C/C) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(xlv) amitriptyline, bupropion, citalopram, fluvoxamine, imipramine, mirtazapine, nortriptyline, venlafaxine, escitalopram, fluoxetine, paroxetine and sertraline if the patient'"'"'s metabolic phenotype is E/E for 2D6 and 2C19, E or I for 3A4, E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is homozygous (s/s);

(xlvi) amitriptyline, bupropion, citalopram, imipramine, mirtazapine, nortriptyline, venlafaxine, escitalopram, fluoxetine, paroxetine and sertraline if the patient'"'"'s metabolic phenotype is E/E for 2D6 and 2C19, E or I for 3A4, I or P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is homozygous (s/s);

(xlvii) amitriptyline, bupropion, citalopram, fluvoxamine, imipramine, mirtazapine, nortriptyline, escitalopram, fluoxetine, paroxetine and sertraline if the patient'"'"'s metabolic phenotype is E/E for 2D6 and 2C19, P for 3A4, E for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is homozygous (s/s);

(xlviii) amitriptyline, bupropion, citalopram, fluvoxamine, imipramine, mirtazapine, nortriptyline, venlafaxine, escitalopram, fluoxetine and sertraline if the patient'"'"'s metabolic phenotype is E/E for 2D6 and 2C19, E or I for 3A4, E for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is homozygous (s/s);

(xlix) amitriptyline, bupropion, citalopram, imipramine, mirtazapine, nortriptyline, escitalopram, fluoxetine, paroxetine and sertraline if the patient'"'"'s metabolic phenotype is E/E for 2D6 and 2C19, P for 3A4, I or P for 1A2, the HTR2A genotype is heterozygous (T/C) or homozygous (T/T) and the 5HTTR genotype is homozygous (s/s);

(l) amitriptyline, bupropion, citalopram, imipramine, mirtazapine, nortriptyline, venlafaxine, escitalopram, fluoxetine and sertraline if the patient'"'"'s metabolic phenotype is E/E for 2D6 and 2C19, E or I for 3A4, I or P for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is homozygous (s/s);

(li) amitriptyline, bupropion, citalopram, fluvoxamine, imipramine, mirtazapine, nortriptyline, escitalopram, fluoxetine and sertraline if the patient'"'"'s metabolic phenotype is E/E for 2D6 and 2C19, P for 3A4, E for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is homozygous (s/s);

or

(lii) amitriptyline, bupropion, citalopram, imipramine, mirtazapine, nortriptyline, escitalopram, fluoxetine and sertraline if the patient'"'"'s metabolic phenotype is E/E for 2D6 and 2C19, P for 3A4, I or P for 1A2, the HTR2A genotype is homozygous (C/C) and the 5HTTR genotype is homozygous (s/s).

7. A non-transitory computer readable medium containing executable instructions that when executed cause a processor to perform operations comprising:

(a) receiving a patient'"'"'s genotype for a panel of genes, wherein said panel comprises

(i) a cytochrome P450 CYP2D6 gene consisting of two alleles independently selected from the group consisting of fully functional alleles 2D6*1A, *2, *2N, and *35, partially functional alleles 2D6*10 and *17, and non-functional alleles 2D6*3, *4, *5, *6, *7, *8, and

(ii) a cytochrome P450 CYP2C19 gene consisting of two alleles independently selected from the group consisting of fully functional alleles 2C19*1A and *1B, and non-functional alleles 2C19*2A, *2B, *3, *4, *5A, *5B, *6, *7 and *8, and

(iii) a serotonin transporter gene 5HTTR consisting of two alleles independently selected from the short (s) and long (l) forms of the 5HTTR gene;

(b) assigning a metabolic phenotype to the patient based on the genotype of the cytochrome P450 genes in (1), wherein the metabolic phenotype is selected from poor (P), intermediate (I), and extensive (E), and said phenotype is assigned based upon the number of functional alleles for each cytochrome P450 gene as follows;

P=no fully functional alleles and either one or no partially functional alleles, I=either one fully functional allele and a non-functional allele or two partially functional alleles, and E=either one fully functional allele and one partially functional allele or two fully functional alleles; and

(c) outputting a list of medications suitable for administering to the patient, said list selected from the group consisting of;

(i) 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 (l/s) or homozygous (l/l);

(ii) bupropion, mirtazapine and fluvoxamine if the patient'"'"'s metabolic phenotype is P/P and the 5HTTR genotype is homozygous (s/s);

(iii) bupropion, mirtazapine, fluvoxamine, sertraline, amitriptyline, nortriptyline, venlafaxine and paroxetine if the patient'"'"'s metabolic phenotype is I/P (intermediate for 2D6 and poor for 2C19) and the 5HTTR genotype is heterozygous (l/s) or homozygous (l/l);

(iv) 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);

(v) 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);

(vi) bupropion, mirtazapine, citalopram, escitalopram, and fluvoxamine if the patient'"'"'s metabolic phenotype is P/E and the 5HTTR genotype is homozygous (s/s);

(vii) 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);

(viii) 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);

(ix) 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);

(x) 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

(xi) 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).

8. The non-transitory computer readable medium of claim 7, further comprising instructions that when executed cause the processor to execute a step of ranking the medications before outputting the list of medications suitable for administering to the patient.

9. The non-transitory computer readable medium of claim 8, wherein the ranking is adjusted based on receiving a clinical response relating to the patient.

10. The non-transitory computer readable medium of claim 9, wherein the clinical response is by a family member of the patient.