Bupropion as a modulator of drug activity
This disclosure relates to administration of a combination of: 1) about 100-110 mg, about 104-106 mg, or about 105 mg or less of bupropion hydrochloride, or a molar equivalent amount of the free base form or another salt form of bupropion; and 2) about 40-50 mg, about 44-46 mg, or about 45 mg or less of dextromethorphan hydrobromide, or a molar equivalent amount of the free base form or another salt form of dextromethorphan in human patients for treating neurological and psychiatric conditions, such as agitation associated Alzheimer's disease and/or reducing relapse of agitation in Alzheimer's disease.
1 . A method of maintaining a clinical response in the treatment of agitation associated with Alzheimer's disease in a human patient, comprising orally administering a dosage form twice a day to the human patient, wherein the human patient has experienced a sustained clinical response as a result of receiving a combination of bupropion and dextromethorphan, wherein a sustained clinical response comprises a 30% or greater improvement from baseline in the human patient's Cohen-Mansfield Agitation Inventory (CMAI) total score which is maintained for at least 4 consecutive weeks, and maintaining a Patient Global Impression of Change (PGI-C) score of 3 or less for at least 4 consecutive weeks, and wherein the dosage form comprises: about 105 mg bupropion hydrochloride, or a molar equivalent amount of the free base or another salt form of bupropion, and about 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of the free base or another salt form of dextromethorphan.
2 . A method of reducing relapse of agitation in Alzheimer's disease in a human patient comprising orally administering a dosage form twice a day to the human patient, wherein the human patient has experienced a sustained clinical response as a result of receiving the dosage form, wherein a sustained clinical response comprises a 30% or greater improvement from baseline in the human patients Cohen-Mansfield Agitation Inventory (CMAI) total score which is maintained for at least 4 consecutive weeks, wherein the dosage form comprises: about 105 mg bupropion hydrochloride, or a molar equivalent amount of the free base or another salt form of bupropion, and about 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of the free base or another salt form of dextromethorphan.
3 . The method of claim 1 , wherein the dosage form comprising about 105 mg of bupropion hydrochloride and about 45 mg of dextromethorphan hydrobromide is orally administered twice a day to the human patient.
4 . The method of claim 1 , wherein the dosage form is administered twice a day for at least 4 weeks.
5 . The method of claim 1 , wherein the dosage form is administered twice a day for at least 3 months.
6 . The method of claim 1 , wherein the dosage form is administered twice a day for at least 6 months.
7 . The method of claim 1 , wherein the dosage form is a solid dosage form.
8 . The method of claim 7 , wherein the solid dosage form further contains a carbomer homopolymer, colloidal silicon dioxide, crospovidone, glyceryl monocaprylocaprate, L-cysteine hydrochloride monohydrate, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, red iron oxide, sodium lauryl sulfate, stearic acid, talc, titanium dioxide, yellow iron oxide, or a combination thereof.
9 . The method of claim 7 , wherein the solid dosage form is a tablet.
10 . The method of claim 9 , wherein the tablet is a bilayer tablet.
11 . The method of claim 1 , wherein dextromethorphan hydrobromide is in an immediate-release formulation.
12 . The method of claim 1 , wherein bupropion hydrochloride is in an extended-release formulation.
13 . The method of claim 11 , wherein bupropion hydrochloride is in an extended-release formulation.
14 . The method of claim 1 , wherein oral administration of the dosage form to the human patient results in a rapid improvement in agitation associated with Alzheimer's disease.
15 . The method of claim 2 , wherein the dosage form comprising about 105 mg of bupropion hydrochloride and about 45 mg of dextromethorphan hydrobromide is orally administered twice a day to the human patient.
16 . The method of claim 2 , wherein the dosage form is administered twice a day for at least 4 weeks.
17 . The method of claim 2 , wherein the dosage form is administered twice a day for at least 3 months.
18 . The method of claim 2 , wherein the dosage form is administered twice a day for at least 6 months.
19 . The method of claim 2 , wherein the dosage form is a solid dosage form.
20 . The method of claim 19 , wherein the solid dosage form further contains a carbomer homopolymer, colloidal silicon dioxide, crospovidone, glyceryl monocaprylocaprate, L-cysteine hydrochloride monohydrate, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, red iron oxide, sodium lauryl sulfate, stearic acid, talc, titanium dioxide, yellow iron oxide, or a combination thereof.
21 . The method of claim 19 , wherein the solid dosage form is a tablet.
22 . The method of claim 21 , wherein the tablet is a bilayer tablet.
23 . The method of claim 2 , wherein dextromethorphan hydrobromide is in an immediate-release formulation.
24 . The method of claim 2 , wherein bupropion hydrochloride is in an extended-release formulation.
25 . The method of claim 23 , wherein bupropion hydrochloride is in an extended-release formulation.
26 . The method of claim 2 , wherein the percentage of human patients with agitation relapse is lower with administration of the dosage form than taking a placebo.
27 . The method of claim 2 , wherein oral administration of the dosage form to the human patient delays the time to relapse of agitation symptoms as compared to a placebo.
28 . The method of claim 2 , wherein oral administration of the dosage form to the human patient delays the time to relapse of agitation symptoms as compared to a placebo with about 3.6-fold lower risk of relapse.
29 . The method of claim 2 , wherein oral administration of the dosage form to the human patient reduces the risk of relapse of agitation in Alzheimer's disease as compared to a placebo.