Methods for selecting initial doses of psychotropic medications based on a CYP2D6 genotype

• US 8,688,385 B2
• Filed: 08/02/2006
• Issued: 04/01/2014
• 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 T
• Application Number:
  US11/498,976
• Publication Number:
  US 20080311563A1
• Time in Patent Office: 2,799 Days
• Field of Search: None
• US Class Current: 702/19
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• 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 2600/112 Disease subtyping, staging or classification
• 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 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 50/00 ICT programming tools or database systems specially adapted for bioinformatics
• CPC Class Codes: G16B 50/30 Data warehousing; Computing architectures
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients

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 initial dose of a psychotropic medication to a patient in need thereof, the initial dose based upon an initial dose recommended in the clinical guidelines for the psychotropic medication, the method comprising:

(1) determining the patient'"'"'s genotype for a panel of cytochrome P450 CYP2D6 alleles selected from the following alleles;

(a) fully functional alleles *1A, *2A, *2N, and *35,

(b) partially functional alleles *2BD, *9, *10, *12,*17, *41, and

(c) non-functional alleles *3, *4, *5, *6, *7, *8, and *11,

(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 initial dose of the psychotropic medication selected from the group consisting of

(a) an initial dose that is half the initial dose recommended in the clinical guidelines if the patient has been assigned a poor (P) metabolic phenotype in step 2; and

(b) an initial dose that is the same as the initial dose recommended in the clinical guidelines if the patient has been assigned an intermediate (I) metabolic phenotype in step 2, provided that the patient is a non-geriatric patient; and

wherein the psychotropic medication is selected from the group consisting of amitriptyline, fluoxetine, imipramine, nortriptyline, paroxetine, and venlafaxine.

2. The method of claim 1, wherein if the patient is a geriatric patient then the initial dose in step 3(b) is half the dose recommended in the clinical guidelines and the initial dose in step 3(c) is the same as the dose recommended in the clinical guidelines.

3. The method of claim 1, wherein the psychotropic medication is venlafaxine.

4. The method of claim 3, wherein the dose recommended in the clinical guidelines is 75 mg.

5. The method of claim 1, wherein the method further comprises receiving, in a computer system, the patient'"'"'s genotype for the panel of cytochrome P450 CYP2D6 alleles, said computer system comprising a database, wherein said database comprises a plurality of psychotropic medication profiles.

6. The method of claim 5, wherein one or more of steps 1 and 2 are performed using said computer system and the method further comprises the step of outputting from the computer system the initial dose of a psychotropic medication for administering to the patient.

7. The method of claim 6, wherein a user enters the patient'"'"'s genotype in the computer system.

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

17. The method of claim 1, wherein the psychotropic medication is selected from the group consisting of fluoxetine, paroxetine, and venlafaxine.

18. The method of claim 1, wherein the psychotropic medication is venlafaxine.

9. A method of preventing an atypical response to a psychotropic medication in a patient in need of a psychotropic medication by administering an initial dose of the psychotropic medication to the patient, the initial dose based upon an initial dose recommended in the clinical guidelines for the psychotropic medication, the method comprising the steps of

(1) determining the patient'"'"'s genotype for a panel of cytochrome P450 CYP2D6 alleles selected from the following alleles:

(a) fully functional alleles *1A, *2A, *2N, and *35,

(b) partially functional alleles *2BD, *9, *10, *12,*17, *41, and

(c) non-functional alleles *3, *4, *5, *6, *7, *8, and *11,

(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 initial dose of the psychotropic medication selected from the group consisting of

(a) an initial dose that is half the initial dose recommended in the clinical guidelines if the patient has been assigned a poor (P) metabolic phenotype in step 2; and

(b) an initial dose that is the same as the initial dose recommended in the clinical guidelines if the patient has been assigned an intermediate (I) metabolic phenotype in step 2, provided that the patient is a non-geriatric patient; and

wherein the psychotropic medication is selected from the group consisting of amitriptyline, fluoxetine, imipramine, nortriptyline, paroxetine, and venlafaxine.

10. 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 cytochrome P450 CYP2D6 alleles selected from the following alleles;

(a) fully functional alleles *1A, *2A, *2N, and *35, (b) partially functional alleles *2BD, *9, *10, *12,*17, *41, and (c) non-functional alleles *3, *4, *5, *6, *7, *8, and *11,

(b) assigning a metabolic phenotype to the patient based on the genotype of the cytochrome P450 genes in (a), 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 an initial dose of a psychotropic medication for the patient, the initial dose based upon an initial dose recommended in the clinical guidelines for the psychotropic medication and selected from the group consisting of

(i) an initial dose that is half the initial dose recommended in the clinical guidelines if the patient has been assigned a poor (P) metabolic phenotype in step (b); and

(ii) an initial dose that is the same as the initial dose recommended in the clinical guidelines if the patient has been assigned an intermediate (I) metabolic phenotype in step (b), provided that the patient is a non-geriatric patient; and

wherein the antidepressant medication is selected from the group consisting of amitriptyline, fluoxetine, imipramine, nortriptyline, paroxetine, and venlafaxine.

11. The non-transitory computer readable medium of claim 10, further comprising a step of ranking the medications before outputting the initial dose of the psychotropic medication.

12. The non-transitory computer readable medium of claim 11, wherein the ranking is adjusted based on receiving a clinical response relating to the patient.

13. The non-transitory computer readable medium of claim 12, wherein the clinical response is by a family member of the patient.

14. The non-transitory computer readable medium of claim 10, wherein if the patient is a geriatric patient then the initial dose in step (c) (ii) is half the dose recommended in the clinical guidelines and the initial dose in step (c) (iii) is the same as the dose recommended in the clinical guidelines.

15. The non-transitory computer readable medium of claim 14, wherein the psychotropic medication is venlafaxine.

16. The non-transitory computer readable medium of claim 15, wherein the dose recommended in the clinical guidelines is 75 mg.