Carbostyril derivatives and mood stabilizers for treating mood disorders

Abstract

The pharmaceutical composition of the present invention comprises a carbostyril derivative which is a dopamine-serotonin system stabilizer and a mood stabilizer in a pharmaceutically acceptable carrier. The carbostyril derivative may be aripiprazole or a metabolite thereof. The mood stabilizer may include but is not limited to lithium, valproic acid, divalproex sodium, carbamazapine, oxcarbamazapine, zonisamide, lamotragine, topiramate, gabapentin, levetiracetam or clonazepam. These compositions are used to treat patients with mood disorders, particularly bipolar disorder with or without psychotic features, mania or mixed episodes. Methods are provided for separate administration of a carbostyril derivative and a mood stabilizer to a patient with a mood disorder.

What is claimed is: 
     
         1 - 16 . (canceled) 
     
     
         17 . A pharmaceutical composition comprising:
 at least one compound selected from aripiprazole, or a metabolite of aripiprazole selected from the group consisting of dehydroaripiprazole, 2,3-dichloro-4-{4-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)-butyl]-piperazin-1-yl}-phenyl sulfate (DM-1458), 7-{4-[4-(2,3-dichloro-4-hydroxyphenyl)-1-piperazinyl]butoxy}-3,4-dihydro-2-(1H)-quinolinone (DM-1451), 7-{4-[4-(2,3-dichiorophenyl)-1-piperazinyl]butoxy}-3,4-dihydro-4-hydroxy-2-(1H)-quinolinone (DM-1452), 1β-(2,3-dichloro-4-{4-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)-butyl]-piperazin-1-yl}-phenoxy)-D-glucopyaranuronic acid (DM-1454) and 1-(2,3-dichlorophenyl)piperazine (DCPP) in combination with at least one mood stabilizer selected from the group consisting of lithium, valproic acid, divalproex sodium, carbamazapine, oxcarbamazapine, zonisamide, lamotragine, topiramate, gabapentin, levetiracetam, clonazepam, and   a salt thereof; and a pharmaceutically acceptable carrier.   
     
     
         18 . The composition of  claim 17 , wherein the at least one compound is aripiprazole. 
     
     
         19 . The composition of  claim 17 , wherein the at least one compound is dehydroaripiprazole, 2,3-dichloro-4-{4-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)-butyl]-piperazin-1-yl}-phenyl sulfate (DM-1458), 7-{4-[4-(2,3-dichloro-4-hydroxyphenyl)-1-piperazinyl]butoxy}-3,4-dihydro-2-(1H)-quinolinone (DM-1451), 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy}-3,4-dihydro-4-hydroxy-2-(1H)-quinolinone (DM-1452), 1β-(2,3-dichloro-4-{4-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)-butyl]-piperazin-1-yl}-phenoxy)-D-glucopyaranuronic acid (DM-1454) or 1-(2,3-dichlorophenyl)piperazine (DCPP). 
     
     
         20 . The composition of  claim 18 , wherein aripiprazole is anhydrous aripiprazole crystals B. 
     
     
         21 . A pharmaceutical composition comprising:
 at least one compound selected from aripiprazole, or a metabolite of aripiprazole selected from the group consisting of dehydroaripiprazole, 2,3-dichloro-4-{4-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)-butyl]-piperazin-1-yl}-phenyl sulfate (DM-1458), 7-{4-[4-(2,3-dichloro-4-hydroxyphenyl)-1-piperazinyl]butoxy}-3,4-dihydro-2-(1H)-quinolinone (DM-1451), 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy}-3,4-dihydro-4-hydroxy-2-(1H)-quinolinone (DM-1452), 1β-(2,3-dichloro-4-{4-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)-butyl]-piperazin-1-yl}-phenoxy)-D-glucopyaranuronic acid (DM-1454) and 1-(2,3-dichlorophenyl)piperazine (DCPP) in combination with at least one mood stabilizer selected from the group consisting of lithium, valproic acid, divalproex sodium, and a salt thereof; and   a pharmaceutically acceptable carrier.   
     
     
         22 . The composition of  claim 21 , wherein the at least one compound is aripiprazole and the at least one mood stabilizer is lithium. 
     
     
         23 . The composition of  claim 21 , wherein the at least one compound is dehydroaripiprazole, 2,3-dichloro-4-{4-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)-butyl]-piperazin-1-yl}-phenyl sulfate (DM-1458), 7-{4-[4-(2,3-dichloro-4-hydroxyphenyl)-1-piperazinyl]butoxy}-3,4-dihydro-2-(1H)-quinolinone (DM-1451), 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy}-3,4-dihydro-4-hydroxy-2-(1H)-quinolinone (DM-1452), 1β(2,3-dichloro-4-{4-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)-butyl]-piperazin-1-yl}-phenoxy)-D-glucopyaranuronic acid (DM-1454) or 1-(2,3-dichlorophenyl)piperazine (DCPP) and the at least one mood stabilizer is lithium. 
     
     
         24 . The composition of  claim 22 , wherein aripiprazole is anhydrous aripiprazole crystals B. 
     
     
         25 . The composition of  claim 21 , wherein the at least one compound is aripiprazole and the at least one mood stabilizer is valproic acid or divalproex sodium. 
     
     
         26 . The composition of  claim 21 , wherein the at least one compound is dehydroaripiprazole, 2,3-dichloro-4-{4-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)-butyl]-piperazin-1-yl}-phenyl sulfate (DM-1458), 7-{4-[4-(2,3-dichloro-4-hydroxyphenyl)-1-piperazinyl]butoxy}-3,4-dihydro-2-(1H)-quinolinone (DM-1451), 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy}-3,4-dihydro-4-hydroxy-2-(1H)-quinolinone (DM-1452), 1β(2,3-dichloro-4-{4-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)-butyl]-piperazin-1-yl}-phenoxy)-D-glucopyaranuronic acid (DM-1454) or 1-(2,3-dichlorophenyl)piperazine (DCPP) in combination with at least one mood stabilizer which is valproic acid or divalproex sodium. 
     
     
         27 . The composition of  claim 25 , wherein aripiprazole is anhydrous aripiprazole crystals B.