Genetic markers for enhancing efficacy of antipsychotic treatment with iloperidone
The present invention relates to the selection of patients with enhanced antipsychotic treatment efficacy with iloperidone based on a patient's genotype at one or more single nucleotide polymorphism (SNP) loci and to treatment of such patients based upon the identification of their genetic information.
1. In a method consisting of administering to a patient suffering from bipolar disorder an amount of a compound selected from iloperidone, a metabolite of iloperidone, or a pharmaceutically acceptable salt of iloperidone or the metabolite thereof, effective to treat a symptom of the bipolar disorder, the improvement comprising:
selecting said patient for treatment based upon a determination that said patient's genotype is selected from the group consisting of : rs2299503-AA, rs13222700-TT, rs11763603-CC, rs7049108-GG, rs579298-TT, rs11176436-TT, and rs17109739-CC.
2. The improvement of claim 1 , wherein the compound is selected from iloperidone or the pharmaceutically acceptable salt thereof.
3. The improvement of claim 1 , wherein the compound is selected from the metabolite of iloperidone or the pharmaceutically acceptable salt thereof.
4. The improvement of claim 3 , wherein the metabolite of iloperidone is P88.
5. A method for treating a patient suffering from bipolar disorder with a compound selected from iloperidone, a pharmaceutically acceptable salt of iloperidone, a metabolite of iloperidone, or a pharmaceutically acceptable salt of the metabolite, comprising:
identifying the patient's genotype at one or more of rs2299503, or rs13222700, rs11763603, rs7049108, rs579298, rs11176436, or rs17109739; and
if the patient has a genotype selected from: rs2299503-AA, rs13222700-TT, rs11763603-CC, rs7049108-GG, rs579298-TT, rs11176436-TT, and rs17109739-CC, then internally administering the iloperidone, the metabolite of iloperidone, or the pharmaceutically acceptable salt of the metabolite to the patient at a first dose, and
if the patient has a genotype selected from: rs2299503-nonAA, rs13222700-nonTT, rs11763603-nonCC, rs7049108-nonGG, rs579298-nonTT, rs11176436-nonTT, and rs17109739-nonCC, then internally administering the iloperidone, the metabolite of iloperidone, or the pharmaceutically acceptable salt of the metabolite to the patient at a second dose that is greater than the first dose.
6. The method according to claim 5 , further comprising:
if the patient has a genotype selected from: rs2299503-nonAA, rs13222700-nonTT, rs11763603-nonCC, rs7049108-nonGG, rs579298-nonTT, rs11176436-nonTT, and rs17109739-nonCC, providing enhanced side-effect and efficacy monitoring for the patient concurrently with or after the internally administering.
7. The method according to claim 5 , wherein the step of identifying comprises:
obtaining or having obtained a biological sample from the patient; and
performing or having performed a genotyping assay on the biological sample to determine the patient's genotype at one or more of rs2299503, rs13222700, rs11763603, rs7049108, rs579298, rs11176436, or rs17109739.
8. The method of claim 5 , wherein the compound is selected from iloperidone or the pharmaceutically acceptable salt thereof.
9. The method of claim 5 , wherein the compound is selected from the metabolite of iloperidone or the pharmaceutically acceptable salt thereof.
10. The method of claim 9 , wherein the metabolite of iloperidone is P88.
11. The method of claim 5 , wherein the first dose is selected from a range of 12 mg/day to 24 mg/day.
12. The method of claim 11 , wherein the first dose is 18 mg/day, and the second dose is selected from 20 mg/day, 22 mg/day, and 24 mg/day.
13. The method of claim 5 , wherein the second dose is greater than a dose the patient would otherwise be administered if the patient's rs2299503, rs1322270, rs11763603, rs7049108, rs579298, rs11176436, and rs17109739 genotypes were unknown.