Bupropion as a modulator of drug activity

Abstract

Dosage forms, drug delivery systems, and methods related to sustained release of dextromethorphan or improved therapeutic effects are disclosed. Typically, bupropion or a related compound is orally administered to a human being to be treated with, or being treated with, dextromethorphan.

What is claimed is: 
     
         1 . A method of rapidly treating major depressive disorder, comprising administering a drug combination to a human being in need thereof, wherein the drug combination comprises:
 a bupropion, in an amount that is about 105 mg of bupropion hydrochloride, or a molar equivalent amount of a bupropion in the free base or another salt form, wherein the bupropion is administered once a day for the first three days and twice a day thereafter for at least 11 days; and   a dextromethorphan, in an amount that is about 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of a dextromethorphan in the free base or another salt form, wherein the dextromethorphan is administered once a day for the first three days and twice a day thereafter for at least 11 days;   wherein the human being is selected for having: moderate to severe major depressive disorder, a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25, and a body mass index of 18 kg/m 2  to 40 kg/m 2 ;   wherein the human being experiences a greater reduction in the MADRS score, as compared to what would be experienced from receiving a placebo, within about 2 weeks of first receiving the drug combination.   
     
     
         2 . The method of  claim 1 , wherein administering the drug combination of the bupropion and the dextromethorphan is more effective in treating major depressive disorder than administering the same amount of the dextromethorphan alone. 
     
     
         3 . The method of  claim 1 , wherein about 105 mg of bupropion hydrochloride and about 45 mg of dextromethorphan hydrobromide are administered once a day for the first three days and twice a day thereafter for at least 11 days to the human being. 
     
     
         4 . The method of  claim 3 , wherein administering the drug combination is more effective in treating major depressive disorder than administering 105 mg of bupropion hydrochloride once a day for the first three days and twice a day thereafter for at least 11 days. 
     
     
         5 . The method of  claim 1 , wherein the dextromethorphan is formulated for immediate release. 
     
     
         6 . The method of  claim 1 , wherein the bupropion is formulated for sustained release. 
     
     
         7 . The method of  claim 1 , wherein the bupropion and the dextromethorphan are administered orally. 
     
     
         8 . The method of  claim 1 , wherein the bupropion is in a solid dosage form. 
     
     
         9 . The method of  claim 1 , wherein the dextromethorphan is in a solid dosage form. 
     
     
         10 . The method of  claim 1 , wherein the human being has a C ave  of bupropion that is at least about 10 ng/mL. 
     
     
         11 . The method of  claim 1 , wherein the human being has a C max  of bupropion that is at least about 90 ng/mL. 
     
     
         12 . The method of  claim 1 , wherein the human being has moderate major depressive disorder. 
     
     
         13 . The method of  claim 1 , wherein the human being has severe major depressive disorder. 
     
     
         14 . The method of  claim 1 , wherein the bupropion and the dextromethorphan are in a single dosage form. 
     
     
         15 . The method of  claim 1 , wherein the bupropion and the dextromethorphan are in separate dosage forms. 
     
     
         16 . The method of  claim 1 , wherein administration of the drug combination results in at least a 10% reduction in the MADRS score as compared with baseline. 
     
     
         17 . The method of  claim 1 , wherein administration of the drug combination results in at least a 10% reduction in the MADRS score as compared to the reduction in the MADRS score that would result from administering placebo. 
     
     
         18 . The method of  claim 1 , wherein the treatment effect on the human being is assessed within two weeks after the drug combination is first administered to the human being. 
     
     
         19 . The method of  claim 1 , wherein the treatment effect on the human being is assessed within one week after the drug combination is first administered to the human being. 
     
     
         20 . A method of rapidly treating major depressive disorder, comprising administering a drug combination to a human being in need thereof, wherein the drug combination comprises:
 a bupropion, in an amount that is about 105 mg of bupropion hydrochloride, or a molar equivalent amount of a bupropion in the free base or another salt form, wherein the bupropion is administered once a day for the first three days and twice a day thereafter for at least 11 days; and   a dextromethorphan, in an amount that is about 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of a dextromethorphan in the free base or another salt form, wherein the dextromethorphan is administered once a day for the first three days and twice a day thereafter for at least 11 days;   wherein the human being is selected for having moderate to severe major depressive disorder that is free of psychotic features, the human being is selected for having a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25, and the human being is selected for not having a psychotic disorder; and   wherein the human being experiences a greater reduction in the MADRS score, as compared to what would be experienced from receiving a placebo, within about 2 weeks of first receiving the drug combination.   
     
     
         21 . The method of  claim 20 , wherein administering the drug combination of the bupropion and the dextromethorphan is more effective in treating major depressive disorder than administering the same amount of the dextromethorphan alone. 
     
     
         22 . The method of  claim 20 , wherein about 105 mg of bupropion hydrochloride and about 45 mg of dextromethorphan hydrobromide are administered once a day for the first three days and twice a day thereafter for at least 11 days to the human being. 
     
     
         23 . The method of  claim 22 , wherein administering the drug combination is more effective in treating major depressive disorder than administering 105 mg of bupropion hydrochloride once a day for the first three days and twice a day thereafter for at least 11 days. 
     
     
         24 . The method of  claim 20 , wherein the dextromethorphan is formulated for immediate release, and the bupropion is formulated for sustained release. 
     
     
         25 . The method of  claim 20 , wherein the bupropion and the dextromethorphan are administered orally. 
     
     
         26 . The method of  claim 20 , wherein the human being has moderate major depressive disorder. 
     
     
         27 . The method of  claim 20 , wherein the human being has severe major depressive disorder. 
     
     
         28 . The method of  claim 20 , wherein administration of the drug combination results in at least a 10% reduction in the MADRS score as compared to the reduction in the MADRS score that would result from administering placebo. 
     
     
         29 . The method of  claim 20 , wherein the treatment effect on the human being is assessed within two weeks after the drug combination is first administered to the human being. 
     
     
         30 . The method of  claim 20 , wherein the treatment effect on the human being is assessed within one week after the drug combination is first administered to the human being.