Compositions and methods for the treatment of addiction and other neuropsychiatric disorders

Abstract

The present invention is based, in part, on our discovery that certain types of therapeutic agents can be used in combination to treat a variety of neuropsychiatric and related disorders, including addiction (e.g., to a substance or to an activity) as well as to alleviate some of the symptoms experienced during menopause or associated with the menstrual cycle. Regardless of the precise formulation, the compositions of the invention can include at least one active ingredient that targets the hypothalamopituitary-adrenal (HPA) axis and at least one active ingredient that targets the prefrontal cortex. Either or both of these types of agents can be combined with an agent that inhibits activity in the sympathetic nervous system. Thus, the compositions or combination pharmacotherapies can also include an agent that inhibits a beta-adrenergic receptor or that otherwise acts as an anti-hypertensive or anxiolytic agent.

1 .- 38 . (canceled) 
     
     
         39 . A method of treating a patient who is suffering from a disorder associated with aberrant activity in the HPA axis, wherein the disorder comprises addiction, schizophrenia, anxiety, or depression, the method comprising: (a) identifying a patient in need of treatment; and (b) administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising
 a first agent that targets the hypothalamo-pituitary-adrenal (HPA) axis and down-regulates the effect of cortisol in the patient and   a second agent selected from the group consisting of a benzodiazepine, mertazapine, gabapentin, muscimol, baclofen, progabide, riluzole, vigabatrin, tiagabine, lamotrigine, carbamazepine, and topiramate, or a pharmaceutically acceptable salt thereof.   
     
     
         40 . The method of  claim 39 , wherein the disorder comprises addiction to a substance. 
     
     
         41 . The method of  claim 40 , wherein the substance is a chemical stimulant, opiate, nicotine, alcohol, prescription pain reliever, or naturally-occurring plant-derived drug. 
     
     
         42 . The method of  claim 41 , wherein the chemical stimulant is cocaine, an amphetamine, a methamphetamine, methylphenidate, or an analog thereof. 
     
     
         43 . The method of  claim 41 , wherein the opiate is heroin, codeine, hydrocodone, or an analog thereof. 
     
     
         44 . The method of  claim 39 , wherein the disorder comprises addiction to an activity. 
     
     
         45 . The method of  claim 44 , wherein the activity is gambling or engaging in a sexual activity. 
     
     
         46 . The method of  claim 39 , wherein the anxiety is associated with panic disorder, obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), social anxiety disorder, or a generalized anxiety disorder. 
     
     
         47 . The method of  claim 39 , wherein the depression is associated with major depressive disorder or dysthymia, is a bipolar depression, or is associated with a medical condition or substance abuse. 
     
     
         48 . The method of  claim 39 , wherein the first agent is a chemical compound or a pharmaceutically acceptable salt thereof. 
     
     
         49 . The method of  claim 39 , wherein the first agent is alpha-helical CRF(9-41) D-Phe CRE12-41, CRF(8-41), CRF(9-41), or CRF(10-41). 
     
     
         50 . The method of  claim 39 , wherein the first agent is metyrapone or ketoconazole or a salt thereof. 
     
     
         51 . The method of  claim 39 , wherein the second agent is a benzodiazepine or a salt thereof. 
     
     
         52 . The method of  claim 51 , wherein the benzodiazepine is oxazepam or chlordiazepoxide. 
     
     
         53 . The method of  claim 39 , wherein the second agent is mirtazapine or a salt thereof. 
     
     
         54 . The method of  claim 39 , wherein the second agent is gabapentin or a salt thereof. 
     
     
         55 . The method of  claim 39 , wherein the second agent is muscimol, progabide, riluzole, baclofen, vigabatrin, tiagabine, lamotrigine, carbamazepine, topiramate, or baclofen or a salt of any of these compounds. 
     
     
         56 . The method of  claim 39 , wherein the pharmaceutical composition is formulated for oral or intravenous administration. 
     
     
         57 . The method of  claim 39 , wherein the pharmaceutical composition comprises about 5-60 mg of oxazepam and about 250-1000 mg of metyrapone in unit dosage form. 
     
     
         58 . The method of  claim 39 , wherein the pharmaceutical composition consists of a first agent, a second agent, one or more physiologically acceptable carriers or excipients, and, optionally, a preservative and/or a substance that increases the solubility of the first agent or the second agent.