Pharmaceutical Compositions Comprising an Antipsychotic Drug and a VMAT2 Inhibitor and Uses Thereof

1 . A method for treating a neuropsychiatric disorder in a subject comprising administering to the subject (a) an antipsychotic drug and (b) a VMAT2 inhibitor, wherein the therapeutically effective amount of the antipsychotic drug administered to the subject is less than the therapeutically effective amount of the antipsychotic drug when administered in the absence of the VMAT2 inhibitor.

2 . The method of claim 1 , wherein the neuropsychiatric disorder is schizophrenia, schizoaffective disorder, bipolar disorder, major depressive disorder (MDD), or autism.

3 . The method of claim 1 , wherein the antipsychotic drug and the VMAT2 inhibitor are administered concurrently.

4 . The method of claim 3 , wherein the antipsychotic drug and the VMAT2 inhibitor are formulated in the same pharmaceutical composition.

5 . The method of claim 1 , wherein the antipsychotic drug is formulated in a first pharmaceutical composition and the VMAT2 inhibitor is formulated in a second pharmaceutical composition.

6 . The method of claim 1 , wherein the antipsychotic drug is a typical antipsychotic drug.

7 . The method of claim 6 , wherein the typical antipsychotic drug is fluphenazine, haloperidol, loxapine, molindone, perphenazine, pimozide, sulpiride, thioridazine, or trifluoperazine.

8 . The method of claim 1 , wherein the antipsychotic drug is an atypical antipsychotic drug.

9 . The method of claim 8 , wherein the atypical antipsychotic drug is aripiprazole, asenapine, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, or ziprasidone.

10 . The method of claim 1 , wherein the therapeutically effective amount of the antipsychotic drug is 10 to 90% less than the therapeutically effective amount of the antipsychotic drug when administered in the absence of the VMAT2 inhibitor.

11 . The method of claim 1 , wherein the therapeutically effective amount of the antipsychotic drug is at least 25% less than the therapeutically effective amount of the antipsychotic drug when administered in the absence of the VMAT2 inhibitor.

12 . The method of claim 1 , wherein the therapeutically effective amount of the antipsychotic drug is at least 50% less than the therapeutically effective amount of the antipsychotic drug when administered in the absence of the VMAT2 inhibitor.

13 . The method of claim 1 , wherein the VMAT2 inhibitor is tetrabenazine (3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one).

14 . The method of claim 1 , wherein the VMAT2 inhibitor is (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b -hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (R,R,R DHTBZ), or a precursor thereof.

15 . The method of claim 1 , wherein the VMAT2 inhibitor is (S)-2-Amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b -hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester.

16 . The method of claim 1 , wherein the VMAT2 inhibitor is [(2R,3S,11bR)-9,10-Dimethoxy-3-(2-methylpropyl)-1H,2H,3H,4H, 6H,7H, 11bH-pyrido[2,1-a]isoquinolin-2-yl]methanol, or a precursor thereof.

17 . The method of claim 1 , wherein the VMAT2 inhibitor is 3-isobutyl-9,10-d 6 -dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one (d 6 -TBZ).

18 - 32 . (canceled)

33 . A method for enhancing efficacy of an antipsychotic drug comprising administering to a subject a combination of (a) the antipsychotic drug, and (b) a VMAT2 inhibitor.

34 . The method of claim 33 , wherein enhancing efficacy of the antipsychotic drug comprises decreasing the amount of the antipsychotic that is therapeutically effective.

35 . The method of claim 33 , wherein the amount of the antipsychotic drug that is therapeutically effective is 10 to 90% less than the amount of the antipsychotic drug that is therapeutically effective when the antipsychotic drug is administered in the absence of the VMAT2 inhibitor.

36 - 60 . (canceled)