Compositions and method for treating depression

Abstract

The present invention describes the combination of a 5HT3-antagonist with pramipexole to reduce or eliminate the adverse effects associated with the use of pramipexole and to enable the use of high doses of pramipexole, useful for treating depressive disorders such as major depressive disorder.

1 . A method for treating a patient suffering from a major depressive disorder, which comprises treating said patient with a 5HT3-antagonist in combination with an effective daily dose of pramipexole or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The method of  claim 1 , wherein, in said combination, said 5HT3-antagonist is administered at a daily dose of from 1 μg to 300 mg. 
     
     
         3 . The method of  claim 1 , wherein said 5HT3-antagonist is selected from the group consisting of azasetron and pharmaceutically salts and solvates thereof, dolasetron and pharmaceutically acceptable salts and solvates thereof, granisetron and pharmaceutically salts and solvates thereof, ondansetron and pharmaceutically salts and solvates thereof, palonosetron and pharmaceutically salts and solvates thereof, ramosetron, and pharmaceutically salts and solvates thereof; and tropisetron and pharmaceutically salts and solvates thereof. 
     
     
         4 . The method of  claim 1 , wherein said pramipexole is pramipexole dihydrochloride monohydrate. 
     
     
         5 . The method of  claim 1 , wherein, in said combination,
 said 5HT3-antagonist is selected from the group consisting of ondansetron or a pharmaceutically acceptable salt thereof, administered at a daily dose equivalent to from 2 mg to 32 mg of ondansetron base; and dolasetron and pharmaceutically acceptable salts thereof, administered at a daily dose equivalent to from 75 mg to 200 mg of dolasetron mesylate; and   said pramipexole or pharmaceutically acceptable salt thereof is administered at a daily dose equivalent to from 0.375 mg to 45 mg of pramipexole dihydrochloride monohydrate.   
     
     
         6 . The method of  claim 5 , wherein, in said combination, said pramipexole or pharmaceutically acceptable salt thereof is administered at a daily dose equivalent to from 1.5 mg to 45 mg of pramipexole dihydrochloride monohydrate. 
     
     
         7 . The method of  claim 5 , wherein, in said combination, said pramipexole or pharmaceutically acceptable salt thereof is administered at a daily dose equivalent to from 5 mg to 45 mg of pramipexole dihydrochloride monohydrate. 
     
     
         8 . The method of  claim 5 , wherein, in said combination, said pramipexole or pharmaceutically acceptable salt thereof is administered at a daily dose equivalent to from 6.5 mg to 45 mg of pramipexole dihydrochloride monohydrate. 
     
     
         9 . The method of  claim 1 , wherein, in said combination, said 5HT3-antagonist and said pramipexole or a pharmaceutically acceptable salt or solvate thereof are each formulated in a pharmaceutical composition in admixture with a pharmaceutical carrier or vehicle. 
     
     
         10 . The method of  claim 1 , wherein, in said combination,
 said 5HT3-antagonist is formulated in a pharmaceutical composition in dosage unit form comprising said 5HT3-antagonist in an amount per unit form of from 0.1 mg to 300 mg, in admixture with a pharmaceutical carrier or vehicle; and   said pramipexole or pharmaceutically acceptable salt thereof is formulated in a pharmaceutical composition in dosage unit form comprising said pramipexole or pharmaceutically acceptable salt thereof in an amount per unit form equivalent to from 0.125 mg to 45 mg of pramipexole dihydrochloride monohydrate, in admixture with a pharmaceutical carrier or vehicle.   
     
     
         11 . The method of  claim 10 , wherein
 said 5HT3-antagonist in said composition is selected from the group consisting of ondansetron and pharmaceutically acceptable salt or solvate thereof, in an amount per unit form equivalent to from 2 mg to 32 mg of ondansetron base, and dolasetron and pharmaceutically acceptable salt or solvate thereof, in an amount per unit form equivalent to from from 25 mg to 200 mg of dolasetron mesylate; and   said pramipexole or pharmaceutically acceptable salt thereof in said composition is present in an amount of from 1.5 mg to 45 mg.   
     
     
         12 . The method of  claim 11 , wherein, in said composition, said pramipexole or pharmaceutically acceptable salt thereof is present in an amount per unit form equivalent to from 5 mg to 45 mg of pramipexole dihydrochloride monohydrate. 
     
     
         13 . The method of  claim 11 , wherein, in said composition, said pramipexole or pharmaceutically acceptable salt thereof is present in an amount per unit form equivalent to from 6.5 mg to 45 mg of pramipexole dihydrochloride monohydrate. 
     
     
         14 . The method of  claim 11 , wherein, in said composition, said pramipexole or pharmaceutically acceptable salt thereof is present in an amount per unit form equivalent to from 6.5 mg to 20 mg of pramipexole dihydrochloride monohydrate. 
     
     
         15 . A 5HT3-antagonist for use in the treatment of major depressive disorders in a patient in need of said treatment, in combination with an effective daily dose of pramipexole or a pharmaceutically acceptable salt thereof. 
     
     
         16 . Use of a 5HT3-antagonist for the preparation of a medicament for the treatment of major depressive disorders in combination with an effective daily dose of pramipexole or pharmaceutically acceptable salt thereof. 
     
     
         17 . The use of  claim 16 , wherein, in said combination, said medicament is a pharmaceutical composition in dosage unit form comprising an effective amount per unit form of said 5HT3-antagonist in admixture with a pharmaceutical carrier or vehicle, and said pramipexole or pharmaceutically acceptable salt thereof also is in a pharmaceutical composition in dosage unit form comprising an effective amount per unit form of said pramipexole or pharmaceutically acceptable salt thereof, in admixture with a pharmaceutical carrier or vehicle. 
     
     
         18 . The use of  claim 17 , wherein said combination is a fixed-dose combination consisting of a pharmaceutical composition in dosage unit form comprising an effective amount per unit of said 5HT3-antagonist, and an effective amount per unit form of said pramipexole or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutical carrier or vehicle.