SOLID ORAL DOSAGE FORMS OF 2R,6R-HYDROXYNORKETAMINE OR DERIVATIVES THEREOF

1 . A method of treating a depressive disorder in a patient comprising:

administering to said patient a solid oral dosage form comprising 2R,6R-hydroxynorketamine or a pharmaceutically acceptable salt thereof, or a prodrug of 2R,6R-hydroxynorketamine having a structure of Formula Ib, or a pharmaceutically acceptable salt thereof

wherein:

(i) R 1 is selected from PO 3 H 2 , SO 3 H, CO 2 H, and R 5 , wherein R 5 is selected from

R 2 is H; or

(ii) R 1 is H;

R 2 is selected from CH 2 OPO 3 H 2 , CH 2 OSO 3 H and R 4 , wherein R 4 is selected from the groups listed in Table 1:

TABLE 1

and;

administering to said patient a serotonin modulator.

2 . The method of claim 1 wherein R 1 is selected from PO 3 H 2 , SO 3 H, CO 2 H, and R 5 , wherein R 5 is selected from

3 . The method of claim 1 wherein R 4 or R 5 has the same stereochemistry as the corresponding L-amino acid.

4 . The method of claim 1 wherein R 1 is PO 3 H 2 .

5 . The method of claim 1 wherein the solid oral dosage form comprises between 10 mg and 100 mg of 2R,6R-hydroxynorketamine, or the equivalent thereof.

6 . The method of claim 1 wherein the solid oral dosage form comprises a crystalline form of 2R,6R-hydroxynorketamine or a pharmaceutically acceptable salt thereof, or a crystalline form of a prodrug of 2R,6R-hydroxynorketamine or a pharmaceutically acceptable salt thereof.

7 . (canceled)

8 . The method of claim 1 wherein the solid oral dosage form is a capsule or a tablet.

9 . The method of claim 1 wherein the solid oral dosage form comprise a blend of one or more diluent.

10 . The method of claim 9 wherein the solid oral dosage form is a tablet and wherein the blend of one or more diluent comprises microcrystalline cellulose.

11 . The method of claim 10 wherein the blend of one or more diluent does not contain lactose monohydrate.

12 . The method of claim 1 wherein the dosage form is a capsule and the capsule shell comprises a constituent selected from gelatin and hydroxypropyl methylcellulose.

13 .- 14 . (canceled)

15 . The wherein said compound and said serotonin modulator are administered simultaneously, sequentially, or separately.

16 . The method of claim 1 wherein said serotonin modulator is selected from Citalopram, Escitalopram, Paroxetine, Fluoxetine, Fluvoxamine, Sertraline, Desvenlafaxine, Duloxetine, Levomilnacipran, Milnacipran, Tofenacin, Venlafaxine, Vilazodone, Vortioxetine, Etoperidone, Nefazodone, and Trazodone, or a pharmaceutically acceptable salt thereof.

17 . The method of claim 16 wherein the serotonin modulator is selected from Citalopram, Escitalopram, Paroxetine, Sertraline, Duloxetine, and Venlafaxine, or a pharmaceutically acceptable salt thereof.

18 . The method of claim 1 wherein the patient has experienced one or more manic episode or hypomanic episode, is suffering a manic episode or hypomanic episode, or is at risk of suffering one or more manic episode or hypomanic episode.

19 . The method of claim 1 wherein the patient is suffering from bipolar depression type 1, bipolar depression type 2, bipolar depression, or obsessive-compulsive disorder comorbid with depression.

20 . The method of claim 1 wherein the solid oral dosage form is for use as a first-line therapy.

21 . The method of claim 1 wherein the solid oral dosage form comprises 2R,6R-hydroxynorketamine L-(+)-tartrate.

22 . The method of claim 1 wherein said pharmaceutically acceptable salt is a tartrate salt.

23 . The method of claim 22 wherein the solid oral dosage form comprise 2R,6R-hydroxynorketamine L-(+)-tartrate.