VAL66MET (SNP rs6265) GENOTYPE SPECIFIC DOSING REGIMENS AND METHODS FOR THE TREATMENT OF DEPRESSION

1 . A method for the treatment of depression, for the treatment of depression in a suicidal patient, for the treatment of suicidality or for the prevention of suicidality, comprising

Step A: genetically testing a patient suffering from depression to determine their Val66Met rs6265 polymorphism in the BDNF gene; and

Step B: administering esketamine according to an induction phase regimen;

wherein the induction phase comprises a treatment period of between 2 and 8 weeks;

wherein the esketamine is administered at a dosing frequency of one to five times per week;

wherein, if the patient is a Val/Val homozygote, then the esketamine is administered at a dosage in an amount in the range of from about 28 mg to about 56 mg;

wherein, if the patient is a Val/Met heterozygote or a Met/Met homozygote, then the esketamine is administered at a dosage in an amount in the range of from about 56 mg to about 84 mg;

and wherein, during the induction phase, the dosage amount or the dosing frequency for the patient who is a Val/Val homozygote and the dosage amount or the dosing frequency for the patient who is a Val/Met heterozygote or Met/Met homozygote is different.

2 . A method as in claim 1 , for the treatment of depression.

3 . A method as in claim 1 , for the treatment of depression, wherein the depression is treatment resistant depression.

4 . A method as in claim 1 , for the treatment of depression in a suicidal patient.

5 . A method as in claim 1 , for the treatment of depression in a suicidal patient, wherein the depression is treatment resistant depression.

6 . A method as in claim 1 for the treatment or prevention of suicidality.

7 . A method as in claim 1 , wherein the esketamine is administered intranasally.

8 . A method as in claim 1 , wherein the induction phase comprises a treatment period of between 2 and 6 weeks.

9 . A method as in claim 1 , wherein the induction phase comprises a treatment period of 4 weeks.

10 . A method as in claim 1 , wherein the esketamine is administered at a dosing frequency of one to three times per week.

11 . A method as in claim 1 , wherein the esketamine is administered at a dosing frequency of one to two times per week.

12 . A method as in claim 1 , wherein, if the patient is a Val/Val homozygote, then the esketamine is administered at a dosage of about 28 mg; and wherein the esketamine is administered at a dosing frequency of twice per week.

13 . A method as in claim 1 , wherein, if the patient is a Val/Met heterozygote or a Met/Met homozygote, then the esketamine is administered at a dosage of about 56 mg; and wherein the esketamine is administered at a dosing frequency of twice per week.

14 . A method as in claim 1 , wherein the esketamine is administered intranasally, wherein the induction phase comprises a treatment period of 4 weeks and wherein the esketamine is administered at a dosing frequency of one to two times per week.

15 . A method for the treatment of depression, for the treatment of depression in a suicidal patient, for the treatment of suicidality or for the prevention of suicidality, comprising

Step A: genetically testing a patient suffering from depression to determine their Val66Met rs6265 polymorphism in the BDNF gene; and

Step B: administering esketamine according to a maintenance phase regimen;

wherein the maintenance phase comprises a treatment period of at least 6 weeks;

wherein, if the patient is a Val/Val homozygote, then the esketamine is administered at a dosage in an amount in the range of from about 28 mg to about 56 mg; and at a dosing frequency in the range of once every two weeks to once every four weeks;

wherein, if the patient is a Val/Met heterozygote or a Mate/Met homozygote, then the esketamine is administered at a dosage in an amount in the range of from about 56 mg to about 84 mg; and at a dosing frequency in the range of once per week to once every two weeks;

wherein, during the maintenance phase, the dosage amount or the dosing frequency for the patient who is a Val/Val homozygote and the dosage amount or the dosing frequency for the patient who is a Val/Met heterozygote or Met/Met homozygote is different;

and wherein the maintenance phase continues until further treatment is not required.

16 . A method as in claim 15 for the treatment of depression.

17 . A method as in claim 15 for the treatment of depression, wherein the depression is treatment resistant depression.

18 . A method as in claim 15 for the treatment of depression in a suicidal patient.

19 . A method as in claim 15 for the treatment of depression in a suicidal patient, wherein the depression is treatment resistant depression.

20 . A method as in claim 15 for the treatment or prevention of suicidality.

21 . A method as in claim 15 , wherein the esketamine is administered intranasally.

22 . A method as in claim 15 , wherein the maintenance phase comprises a treatment period of at least 8 weeks.

23 . A method as in claim 15 , wherein the maintenance phase comprises a treatment period of at least 12 weeks.

24 . A method as in claim 15 , wherein if the patient is a Val/Val homozygote, then the esketamine is administered at a dosage of 28 mg; and wherein the esketamine is administered at a dosing frequency of once every two weeks.

25 . A method as in claim 15 , wherein if the patient is a Val/Met heterozygote or a Met/Met homozygote, then the esketamine is administered at a dosage of 56 mg; and wherein the esketamine is administered at a dosing frequency of once per week.

26 . A method as in claim 15 , wherein the esketamine is administered at the lowest dosing frequency at which an antidepressant response is maintained.

27 . A method as in claim 15 , wherein the esketamine is administered at the lowest dosage amount at which an antidepressant response is maintained.

28 . A method as in claim 15 , wherein the esketamine is administered intranasally; wherein if the patient is a Val/Val homozygote, then the esketamine is administered at a dosage of 28 mg and at a dosing frequency of once every two weeks; and wherein if the patient is a Val/Met heterozygote or a Met/Met homozygote, then the esketamine is administered at a dosage of 56 mg and at a dosing frequency of once per week.

29 . A method for the treatment of depression, for the treatment of depression in a suicidal patient, for the treatment of suicidality or for the prevention of suicidality, comprising

Step A: genetically testing a patient suffering from depression to determine their Val66Met rs6265 polymorphism in the BDNF gene; and

Step B: administering an esketamine dosing regimen; wherein the esketamine dosing regimen comprises

(i) an induction dosing phase;

wherein the induction phase comprises a treatment period of between 2 and 8 weeks;

wherein the esketamine is administered at a dosing frequency of one to five times a week;

wherein, if the patient is a Val/Val homozygote, then the esketamine is administered at a dosage in an amount in the range of from about 28 mg to about 56 mg;

wherein, if the patient is a Val/Met heterozygote or a Met/Met homozygote, then the esketamine is administered at a dosage in an amount in the range of from about 56 mg to about 84 mg;

and wherein, during the induction phase, the dosage amount or the dosing frequency for the patient who is a Val/Val homozygote and the dosage amount or the dosing frequency for the patient who is a Val/Met heterozygote or Met/Met homozygote is different;

and (b) a maintenance phase;

wherein the maintenance phase comprises a treatment period of at least 6 weeks;

wherein, if the patient is a Val/Val homozygote, then the esketamine is administered at a dosage in an amount in the range of from about 28 mg to about 56 mg; and at a frequency in the range of once every two weeks to once every four weeks;

wherein, if the patient is a Val/Met heterozygote or a Mate/Met homozygote, then the esketamine is administered at a dosage in an amount in the range of from about 56 mg to about 84 mg; and at a frequency in the range of once per week to once every two weeks;

and wherein, during the maintenance phase, the dosage amount or the dosing frequency for the patient who is a Val/Val homozygote and the dosage amount or the dosing frequency for the patient who is a Val/Met heterozygote or Met/Met homozygote is different;

and wherein the maintenance phase continues until further treatment is not required.

30 . A method as in claim 29 for the treatment of depression.

31 . A method as in claim 29 for the treatment of depression, wherein the depression is treatment resistant depression.

32 . A method as in claim 29 for the treatment of depression in a suicidal patient.

33 . A method as in claim 29 for the treatment of depression in a suicidal patient, wherein the depression is treatment resistant depression.

34 . A method as in claim 29 for the treatment or prevention of suicidality.

35 . A method as in claim 29 , wherein the esketamine is administered intranasally.

36 . A method as in claim 29 , wherein the induction phase comprises a treatment period of between 2 and 6 weeks.

37 . A method as in claim 29 , wherein the induction phase comprises a treatment period of 4 weeks.

38 . A method as in claim 29 , wherein during the induction phase, the esketamine is administered at a dosing frequency of one to three times per week.

39 . A method as in claim 29 , wherein during the induction phase the esketamine is administered at a dosing frequency of one to two times per week.

40 . A method as in claim 29 , wherein during the induction phase, if the patient is a Val/Val homozygote, then the esketamine is administered at a dosage of about 28 mg and at a dosing frequency of twice per week.

41 . A method as in claim 29 , wherein during the induction phase, if the patient is a Val/Met heterozygote or a Met/Met homozygote, then the esketamine is administered at a dosage of about 56 mg and at a dosing frequency of twice per week.

42 . A method as in claim 29 , wherein the maintenance phase comprises a treatment period of at least 8 weeks.

43 . A method as in claim 29 , wherein the maintenance phase comprises a treatment period of at least 12 weeks.

44 . A method as in claim 29 , wherein during the maintenance phase, if the patient is a Val/Val homozygote, then the esketamine is administered at a dosage of 28 mg and at a dosing frequency of once every two weeks.

45 . A method as in claim 29 , wherein during the maintenance phase, if the patient is a Val/Met heterozygote or a Met/Met homozygote, then the esketamine is administered at a dosage of 56 mg and at a dosing frequency of once per week.

46 . A method as in claim 29 , wherein during the maintenance phase, the esketamine is administered at the lowest dosing frequency at which an antidepressant response is maintained.

47 . A method as in claim 29 , wherein during the maintenance phase, the esketamine is administered at the lowest dosage amount at which an antidepressant response is maintained.

48 . A method for the treatment of treatment resistant depression or for the treatment of depression in a suicidal patient, comprising

Step A: genetically testing a patient suffering from depression to determine their Val66Met rs6265 polymorphism in the BDNF gene; and

Step B: administering an esketamine dosing regimen; wherein the esketamine is administered intranasally; and wherein the dosing regimen comprises

(i) an induction dosing phase;

wherein the induction phase comprises a treatment period of 4 weeks;

wherein the esketamine is administered at a dosing frequency of one to two times per week;

wherein, if the patient is a Val/Val homozygote, then the esketamine is administered at a dosage of about 28 mg;

wherein, if the patient is a Val/Met heterozygote or a Met/Met homozygote, then the esketamine is administered at a dosage of about 56 mg;

and wherein, during the induction phase, the dosage amount or the dosing frequency for the patient who is a Val/Val homozygote and the dosage amount or dosing frequency for the patient who is a Val/Met heterozygote or Met/Met homozygote is different;

and (b) a maintenance phase;

wherein the maintenance phase comprises a treatment period of at least 12 weeks;

wherein, if the patient is a Val/Val homozygote, then the esketamine is administered at a dosage in an amount of about 28 mg and at a dosing frequency of once every two weeks;

wherein, if the patient is a Val/Met heterozygote or a Met/Met homozygote, then the esketamine is administered at a dosage in an amount of about 56 mg and at a dosing frequency of once per week;

wherein during the maintenance phase, the dosage amount or the dosing frequency for the patient who is a Val/Val homozygote and the dosage amount or the dosing frequency for the patient who is a Val/Met heterozygote or Met/Met homozygote is different.

49 . A method for the treatment of depression, for the treatment of depression in a suicidal patient, for the treatment of suicidality or for the prevention of suicidality, as herein described.

50 . A dosing regimen for the treatment of depression, for the treatment of depression in a suicidal patient, for the treatment of suicidality or for the prevention of suicidality, as herein described.