Methods for the treatment of abnormal involuntary movement disorders

Abstract

Disclosed herein are new dosage regimens for deuterium-substituted benzoquinoline compounds, and methods for the treatment of abnormal muscular activity, movement disorders, and related conditions.

What is claimed is: 
     
         1 . A method of treating abnormal involuntary movement in a subject with impaired CYP2D6 metabolism, comprising:
 administering to the subject a total daily dose of deutetrabenazine of less than or equal to about 48 mg.   
     
     
         2 . The method of  claim 1 , wherein the total daily dose of deutetrabenazine is less than 48 mg. 
     
     
         3 . The method of  claim 1 , wherein the total daily dose of deutetrabenazine is less than or equal to about 36 mg. 
     
     
         4 . The method of  claim 1 , wherein the total daily dose of deutetrabenazine is less than about 36 mg. 
     
     
         5 . The method of  claim 1 , wherein the subject is concurrently receiving a strong CYP2D6 inhibitor. 
     
     
         6 . The method of  claim 5 , wherein the strong CYP2D6 inhibitor is fluoxetine, paroxetine, bupropion, quinidine, cinacalcet, or ritonavir. 
     
     
         7 . The method of  claim 5 , wherein the strong CYP2D6 inhibitor is paroxetine, fluoxetine, or bupropion. 
     
     
         8 . The method of  claim 1 , wherein the subject's impaired CYP2D6 metabolism is genetic. 
     
     
         9 . The method of  claim 1 , resulting in no clinically significant adverse event in the subject. 
     
     
         10 . The method of  claim 1 , resulting in no significant increase in insomnia, depression, anxiety, agitation, suicidal ideation, akathisia, irritability, fatigue, parkinsonism or dysphagia in the subject. 
     
     
         11 . The method of  claim 1 , wherein the abnormal involuntary movement is caused by a movement disorder. 
     
     
         12 . The method of  claim 11 , wherein the movement disorder is akathisia, akinesia, ataxia, athetosis, ballismus, bradykinesia, cerebral palsy, chorea, corticobasal degeneration, dyskinesias (e.g., paroxysmal), dystonia (general, segmental, or focal) including blepharospasm, writer's cramp (limb dystonia), laryngeal dystonia (spasmodic dysphonia), and oromandibular dystonia, essential tremor, geniospasm, hereditary spastic paraplegia, Huntington's Disease, multiple system atrophy (Shy Drager Syndrome), myoclonus, Parkinson's Disease, Parkinson's disease levodopa-induced dyskinesia, parkinsonism, progressive supranuclear palsy, restless legs syndrome, Rett Syndrome, spasmodic torticollis (cervical dystonia), spasticity due to stroke, cerebral palsy, multiple sclerosis, spinal cord or brain injury, stereotypic movement disorder, stereotypy, Sydenham's Chorea, synkinesis, tardive dyskinesia, dystonia, tics, Tourette syndrome, or Wilson's Disease. 
     
     
         13 . The method of  claim 11 , wherein the movement disorder is a hyperkinetic movement disorder. 
     
     
         14 . The method of  claim 11 , wherein the movement disorder is Huntington's disease, tardive dyskinesia, Tourette syndrome, dystonia, or Parkinson's disease levodopa-induced dyskinesia. 
     
     
         15 . The method of  claim 11 , wherein the movement disorder is Huntington's disease, tardive dyskinesia, or Tourette syndrome. 
     
     
         16 . The method of  claim 11 , wherein the movement disorder is Huntington's disease. 
     
     
         17 . The method of  claim 1 , wherein the abnormal involuntary movement is chorea, akathisia, dyskinesia, tremor, or tic. 
     
     
         18 . The method of  claim 1 , wherein the total daily dose of deutetrabenazine is administered in two doses. 
     
     
         19 . The method of  claim 1 , resulting in an improvement in balance, physical functioning, or swallowing in the subject. 
     
     
         20 . The method of  claim 19 , wherein the subject's physical functioning is improved as measured by the SF-36 physical functioning scale after baseline. 
     
     
         21 . The method of  claim 1 , resulting in an improvement in motor function in the subject. 
     
     
         22 . The method of  claim 21 , wherein the motor function in the subject is improved by a reduction of at least 1 point as measured by the Total Motor Score (TMS) of the Unified Huntington's Disease Rating Scale (UHDRS). 
     
     
         23 . The method of  claim 22 , wherein the reduction in TMS Score is at least 2, 3, or 4 points. 
     
     
         24 . The method of  claim 1 , further comprising administering to the subject another therapeutic agent useful in the treatment of VMAT2-mediated disorders. 
     
     
         25 . The method of  claim 1 , wherein the subject is human.