Olanzapine-N-oxide compositions and methods

Abstract

Methods and compositions are disclosed utilizing olanzapine-N-oxide for the treatment of psychosis in humans. Olanzapine-N-oxide exhibits a lessened liability toward drug-drug interactions than olanzapine and a more predictable dosing regimen than olanzapine. Olanzapine-N-oxide is also useful for the treatment of acute mania, mild anxiety states, anxiety disorders, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, autistic disorder, excessive aggression, substance abuse, depressive signs and symptoms, tic disorder, functional bowel disorder and fungal dermatitis.

What is claimed is:  
     
         1 . A method of treating psychosis which comprises administering to a human a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof.  
     
     
         2 . The method according to  claim 1 , wherein schizophrenia is treated.  
     
     
         3 . The method according to  claim 1 , wherein acute mania is treated.  
     
     
         4 . A method of treating mild anxiety states which comprises administering to a human a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof.  
     
     
         5 . A method of treating bipolar disorder which comprises administering to a human a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof.  
     
     
         6 . A method of treating autistic disorder which comprises administering to a human a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof.  
     
     
         7 . A method of treating attention deficit hyperactivity disorder which comprises administering to a human a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof.  
     
     
         8 . A method of treating excessive aggression which comprises administering to a human a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof.  
     
     
         9 . A method of treating substance abuse which comprises administering to a human a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof.  
     
     
         10 . A method of treating depressive signs and symptoms which comprises administering to a human a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof.  
     
     
         11 . A method of treating tic disorder which comprises administering to a human a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof.  
     
     
         12 . A method of treating functional bowel disorder which comprises administering to a human a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof.  
     
     
         13 . A method of treating fungal dermatitis which comprises administering to a human a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof.  
     
     
         14 . A method of treating anxiety disorder which comprises administering to a human a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof.  
     
     
         15 . The method according to  claim 14 , wherein the anxiety disorder is selected from the group consisting of obsessive-compulsive disorder, post-traumatic stress disorder, psychoactive substance disorder, generalized anxiety disorder, organic anxiety disorder, and anxiety disorder NOS.  
     
     
         16 . The method of any of  claim 1  wherein olanzapine-N-oxide is administered orally.  
     
     
         17 . The method of  claim 16  wherein the amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof administered is from about 1 mg to about 150 mg per day.  
     
     
         18 . The method of any of  claim 1  wherein olanzapine-N-oxide is administered in combination with a therapeutically effective amount of a selective serotonin reuptake inhibitor.  
     
     
         19 . The method of any of  claim 1  wherein 2-hydroxymethylolanzapine is administered in combination with a drug chosen from paroxetine, fluoxetine, sertaline, fluvoxamine, venlafaxine and nefazodone.  
     
     
         20 . A pharmaceutical composition comprising olanzapine-N-oxide, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.  
     
     
         21 . A pharmaceutical composition according to  claim 20  comprising a pharmaceutically acceptable carrier for oral therapy and a therapeutically effective amount of olanzapine-N-oxide or a pharmaceutically acceptable salt thereof in the form of a tablet or capsule.  
     
     
         22 . A pharmaceutical composition according to  claim 20 , additionally comprising a therapeutically effective amount of a selective serotonin reuptake inhibitor compound or a pharmaceutically acceptable salt thereof.  
     
     
         23 . A pharmaceutical composition according to  claim 20 , additionally comprising a therapeutically effective amount of a drug chosen from paroxetine, fluoxetine, sertaline, fluvoxamine, venlafaxine and nefazodone.