Methods of monitoring for adherence to aripiprazole therapy

1. A method for recommending a modification to an aripiprazole therapy, the method comprising:

identifying a subject who is prescribed aripiprazole therapy;

determining a prescribed aripiprazole dose associated with the prescribed aripiprazole therapy;

measuring a concentration of OPC3373 and a creatinine level in urine of the subject;

normalizing the concentration of OPC3373 as a function of the creatinine level;

identifying the subject as non-adherent to aripiprazole therapy if the normalized concentration of OPC3373 is less than a predetermined level, and as adherent to aripirazole therapy if the normalized concentration of OPC3373 is greater than the predetermined level; and

recommending a modification to the prescribed aripiprazole dose if the subject is identified as non-adherent, wherein the modification comprises a discontinuation of the aripiprazole therapy or a replacement of the aripiprazole therapy with a new therapeutic regimen.

2. The method of claim 1 further comprising counseling the subject on dangers of non-adherence to aripiprazole therapy if the subject is identified as non-adherent.

3. The method of claim 1 , wherein the predetermined level is 25 ng/mL.

4. The method of claim 1 , wherein the aripiprazole therapy comprises prescribing to the subject aripiprazole in an amount selected from the group consisting of: 2 mg/day, 5 mg/day, 10 mg/day, 15 mg/day, 20 mg/day, or 30 mg/day.

5. The method of claim 1 , wherein the concentration of OPC3373 is measured by LC/MSMS.

6. The method of claim 1 , wherein the concentration of OPC3373 is measured by LC/MS(TOF).

7. The method of claim 1 , wherein the concentration of OPC3373 is measured by direct administration to a mass spectrometer.

8. The method of claim 7 , wherein the direct administration comprises Rapidfire or laser diode thermal desorption (“LDTD”).

9. The method of claim 1 further comprising:

measuring a concentration of aripiprazole in urine of the subject, wherein the subject is identified as non-adherent if the concentrations of aripiprazole and OPC3373 are both less than predetermined levels of aripiprazole and OPC3373, respectively.

10. The method of claim 9 , wherein the predetermined level of aripiprazole is 5 ng/mL.

11. The method of claim 9 , wherein the predetermined level of OPC3373 is 25 ng/mL.

12. The method of claim 9 further comprising:

measuring a concentration of dehydroaripiprazole in urine of the subject, wherein the subject is identified as non-adherent if the concentration aripiprazole, dehydroaripiprazole and OPC3373 are each less than predeteimined levels of aripiprazole, dehydroaripiprazole and OP3173, respectively.

13. The method of claim 12 , wherein the predetermined level of dehydroaripprazole is 5 ng/mL.

14. The method of claim 12 , wherein the predetermined level of aripiprazole is 5 ng/mL.

15. The method of claim 12 , the predetermined level of OPC3373 is 25 ng/mL.

16. The method of claim 12 , wherein the concentration of OPC3373 is measured by LC/MSMS.

17. The method of claim 1 further comprising:

measuring a concentration of dehydroaripiprazole in urine of the subject, wherein the subject is identified as non-adherent if the concentrations of dehydroaripiprazole and OPC3373 are both less than predetermined levels of dehydroaripiprazole and OPC3373, respectively.

18. The method of claim 17 , wherein the predetermined level of dehydroaripiprazole is 5 ng/mL.

19. The method of claim 17 , wherein the predetermined level of OPC3373 is 25 ng/mL.

20. The method of claim 17 , wherein the concentration of OPC3373 is measured by LC/MSMS.

21. The method of claim 1 wherein the predetermined level comprises a ratio of the OPC3373 concentration to the creatinine level.

22. The method of claim 21 further comprising:

measuring an aripiprazole concentration in urine of the subject and optionally a specific gravity value; and

normalizing the aripiprazole concentration as a function of the creatinine level and/or the specific gravity value,

wherein the predetermined level comprises a ratio of the normalized OPC3373 concentration and/or the aripiprazole concentration to the creatinine level and/or the specific gravity value.

23. The method of claim 21 further comprising:

measuring a dehydroaripiprazole concentration in urine of the subject; and

normalizing the dehydroaripiprazole concentration as a function of the creatinine level and/or a specific gravity value,

wherein the predetermined level comprises a ratio of the dehydroaripiprazole concentration to the creatinine level and/or the specific gravity value.

24. The method of claim 1 further comprising:

generating a normal distribution of OPC3373 in aripiprazole subjects using a log of a plurality of normalized OPC3373 concentrations in urine of a plurality of subjects who have received aripiprazole therapy and are known to have been adherent.

25. The method of claim 24 further comprising:

identifying a normalized concentration of OPC3373 in urine of the subject as normal if it falls within the normal distribution of OPC3373 in aripiprazole subjects; and/or

identifying the normalized concentration of OPC3373 in urine of the subject as not normal if it falls outside the normal distribution of OPC3373 in aripiprazole subjects.

26. The method of claim 25 , further comprising generating a second, refinednormal distribution of OPC3373 in aripiprazole subjects using the normalized OPC3373 concentration in urine of the subject if it is identified as normal.

27. The method of claim 1 further comprising:

measuring an aripiprazole concentration in urine of each of a plurality of aripiprazole subjects known to be adherent; and

generating a normal distribution of aripirazole in aripiprazole subjects using a log of a plurality of aripiprazole concentrations in urine of the plurality of subjects.

28. The method of claim 27 further comprising:

measuring an aripiprazole concentration in the subject; and

identifying the aripiprazole concentration in urine of the subject; as normal if it falls within the normal distribution of aripiprazole in aripiprazole subjects; and/or

identifying the aripiprazole concentration in urine of the subject as not normal if it falls outside the normal distribution of aripiprazole in aripiprazole subjects.

29. The method of claim 28 further comprising generating a second, refined normal distribution of aripiprazole in aripiprazole subjects using the aripiprazole concentration in urine of the subject if it is identified as normal.

30. The method of claim 1 further comprising:

measuring a dehydroaripiprazole concentration in urine of each of a plurality of aripiprazole subjects known to be adherent; and

generating a normal distribution of dehydroaripiprazole inaripiprazole subjects using a log of the dehydroaripiprazole concentrations in urine of the plurality of aripiprazole subjects.

31. The method of claim 30 further comprising:

measuring a dehydroaripiprazole concentration in the subject; and

identifying the dehydroaripiprazole concentration as normal if it falls within the normal distribution of dehydroaripiprazole in aripiprazole subjects; and/or

identifying the dehydroaripiprazole concentration as not normal if it falls outside the normal distribution of dehydroaripiprazole in aripiprazole subjects.

32. The method of claim 31 further comprising generating a second, refined normal distribution of dehydroaripiprazole in aripiprazole subjects using the dehydroaripiprazole concentration of the subject if it is identified as normal.

33. The method of claim 1 further comprising recommending maintaining the prescribed aripiprazole dose if the subject is identified as adherent.

34. The method of claim 33 , wherein the step of recommending maintaining the prescribed aripiprazole dose comprises recommending no modification to the prescribed aripiprazole dose.

35. The method of claim 33 , wherein the step of recommending maintaining the prescribed aripiprazole dose comprises recommending no significant modification to the prescribed aripiprazole dose.