COMPOSITIONS OF 5-HT3 ANTAGONISTS AND DOPAMINE D2 ANTAGONISTS FOR TREATMENT OF DOPAMINE-ASSOCIATED CHRONIC CONDITIONS
The present invention provides novel compositions comprising a combination of a 5-HT 3 receptor antagonist and a selective dopamine D 2 receptor antagonist for the treatment of alcohol dependence and other dopamine pathway-associated disorders or conditions. Preferably, the pharmaceutical compositions of the present invention comprise amounts of the 5-HT 3 receptor antagonist ondansetron and the selective dopamine D 2 receptor antagonist olanzapine that are sufficient to control a subject's craving for alcohol or other addictive substances. Kits comprising the combination of antagonists for the treatment of addictive disorders such as alcohol dependence are also provided.
1 . A method for treating alcohol dependence in a patient, said method comprising the steps of:
providing a pharmaceutical composition comprising about 0.2 to about 8.0 mg of ondansetron and about 0.5 to about 7.5 mg of olanzapine; and
administering the composition to the patient.
2 . The method of claim 1 , wherein the pharmaceutical composition comprises about 0.2 to about 8.0 mg of ondansetron.
3 . The method of claim 1 , wherein the pharmaceutical composition comprises about 1 mg of olanzapine.
4 . The method of claim 1 , wherein the pharmaceutical composition comprises about 5 mg of olanzapine.
5 . The method of claim 1 , wherein the pharmaceutical composition comprises about 0.325 mg of ondansetron.
6 . The method of claim 1 , wherein the pharmaceutical composition comprises about 0.65 mg of ondansetron.
7 . The method of claim 1 , wherein following a four week or more treatment the patient has less than eight drinks per day.
8 . The method of claim 1 , wherein following a four week or more treatment the patient has less than six drinks per day.
9 . The method of claim 1 , wherein following a four week or more treatment the patient has less than four drinks per day.
10 . The method of claim 1 , wherein following a four week or more treatment the patient has less than 60% heavy drinking days.
11 . The method of claim 1 , wherein following a four week or more treatment the patient has less than 50% heavy drinking days.
12 . The method of claim 1 , wherein following a four week or more treatment the patient has less than 40% heavy drinking days.
13 . The method of claim 1 , wherein the steady state plasma concentration of olanzapine is at least 0.5 ng/ml.
14 . The method of claim 1 , wherein the steady state plasma concentration of olanzapine is at least 1.5 ng/ml.
15 . The method of claim 1 , wherein the steady state plasma concentration of olanzapine is no greater than 10.0 ng/ml.
16 . The method of claim 1 , wherein the steady state plasma concentration of ondansetron is at least 0.2 ng/ml.
17 . The method of claim 1 , wherein the steady state plasma concentration of ondansetron is no greater than 1.2 ng/ml.
18 . A method for reducing the craving for alcohol in a patient, said method comprising the steps of:
providing a pharmaceutical composition comprising about 0.2 to about 8.0 mg of ondansetron and about 0.5 to about 7.5 mg of olanzapine; and
administering the composition to the patient,
wherein following a four week or more treatment the patient has less than eight drinks per day.
19 . The method of claim 19 , wherein following a four week or more treatment the patient has less than six drinks per day.
20 . The method of claim 19 , wherein following a four week or more treatment the patient has less than four drinks per day.