Treatments for depression and other diseases with a low dose agent

Abstract

The present invention relates to improved compositions and methods for the treatment or prevention of various diseases, including forms of depression, including, for example, breakthrough depression and treatment-refractory depression, and other mood disorders, as well as Parkinson's disease, bipolar disorder, bipolar disorder, attention deficit disorder (ADHD), Restless Leg Syndrome (RLS), and obesity. In some embodiments, the compositions and methods comprise low dose naltrexone or related opioid antagonists.

1 .- 90 . (canceled) 
     
     
         91 . A method for treating treatment resistant depression (TRD), comprising administering a therapeutically effective low dose amount of naltrexone to a human patient in need thereof, wherein:
 the low dose amount of naltrexone is about 1-4 mg;   the patient is undergoing treatment for TRD comprising at least one dopaminergic agent; and   the dopaminergic agent is bupropion.   
     
     
         92 . The method of  claim 91 , wherein the TRD is a major depressive disorder (MDD). 
     
     
         93 . The method of  claim 91  or  92 , wherein the TRD is relapsing. 
     
     
         94 . The method of  claim 91  or  92 , wherein the TRD is recurrent. 
     
     
         95 . The method of  claim 91  or  92 , wherein the TRD is breakthrough depression. 
     
     
         96 . The method of  claim 91 , wherein the dose of bupropion is at least 300 mg/day. 
     
     
         97 . The method of  claim 91  or  96 , wherein the bupropion is an extended-release (XL) form. 
     
     
         98 . The method of  claim 91  or  96 , wherein the low dose amount of naltrexone is about 1 mg. 
     
     
         99 . The method of  claim 91  or  96 , wherein the low dose amount of naltrexone is administered once daily for at least three weeks. 
     
     
         100 . The method of  claim 91  or  96 , wherein the low dose amount of naltrexone is administered twice daily for at least three weeks. 
     
     
         101 . The method of  claim 91  or  96 , wherein the administering is oral. 
     
     
         102 . The method of  claim 91 , wherein the treating results in a reduction in the patient's Hamilton Rating Scale for Depression (HAM-D-17) score. 
     
     
         103 . The method of  claim 91  or  102 , wherein the treating results in a Hamilton Rating Scale for Depression (HAM-D-17) score of less than 15. 
     
     
         104 . The method of  claim 91 , wherein the treating results in a reduction in the patient's Montgomery-Asberg Depression Rating Scale (MADRS-10) score. 
     
     
         105 . The method of  claim 91  or  104 , wherein the treating results in a Montgomery-Asberg Depression Rating Scale (MADRS-10) score of less than 15. 
     
     
         106 . The method of  claim 91 , wherein the treating results in a reduction in the patient's Clinical Global Impressions Improvement (CGI-I) score. 
     
     
         107 . The method of  claim 91  or  106 , wherein the treating results in a Clinical Global Impressions Improvement (CGI-I) score of less than 3. 
     
     
         108 . The method of  claim 91 , wherein the treating comprises a reduction in a rate of relapse after a major depressive episode. 
     
     
         109 . The method of  claim 91 , wherein the treating comprises reduction in length of a depressive episode. 
     
     
         110 . The method of  claim 91 , wherein the treating comprises recovery of an anti-depressive effect of a pre-existent anti-depression treatment. 
     
     
         111 . The method of  claim 91 , wherein the treating comprises prevention of loss of efficacy of an anti-depression treatment. 
     
     
         112 . The method of  claim 91 , wherein treating comprises a rapid antidepressant response compared to a usual latency for response to a traditional antidepressant treatment. 
     
     
         113 . The method of  claim 112 , wherein the rapid antidepressant response is less than about 10 days. 
     
     
         114 . A method for treating breakthrough treatment resistant depression (TRD), comprising orally administering a therapeutically effective low dose amount of naltrexone to a human patient having a remission for at least 3 months followed by a relapse or recurrence, wherein:
 the low dose amount of naltrexone is about 1-4 mg, administered once or twice daily for at least three weeks;   the patient is undergoing treatment for TRD comprising bupropion; and   the treating causes a reduction in the patient's Hamilton Rating Scale for Depression (HAM-D-17) score to less than 15 within three weeks or less from beginning of administration of the low dose amount of naltrexone.   
     
     
         115 . The method of  claim 114 , wherein an antidepressant response is observed within three weeks from beginning of administration of the low dose amount of naltrexone. 
     
     
         116 . The method of  claim 114 , wherein the dose of bupropion is at least 300 mg/day. 
     
     
         117 . The method of  claim 114  or  116 , wherein the bupropion is an extended-release (XL) form.