title: Emerging drugs for antipsychotic-induced tardive dyskinesia: investigational drugs in Phase II and Phase III clinical trials.
abstract: BACKGROUND
  Antipsychotic drugs (APs) represent the mainstay of treatment for schizophrenia and other forms of psychosis. Tardive dyskinesia (TD) is a motor disorder associated with the ongoing use of APs and is characterized by involuntary, repetitive movements that are potentially irreversible. Current treatment is wanting, due in part to our limited understanding of the mechanisms underlying TD.
  
  
  METHODS
  Risk of TD associated with APs appears linked to continuous blockade of dopamine D2 receptors in the basal ganglia. Proposed mechanisms include increased dopamine activation of D2 receptors caused by supersensitivity and neurodegeneration of dopamine-producing neurons due to biochemical changes incurred by ongoing AP exposure. Existing treatments are designed to reverse or prevent the neurochemical/biological changes caused by dopamine D2 receptor blockade and include vesicular monoamine transporter (VMAT) inhibitors, antioxidants, compounds with serotonin receptor agonism as well as antagonism, GABA agonists and cholinergic agents. Randomized, controlled trials in Phase II and Phase III (ClinicalTrials.org/ClinicalTrialsRegister.eu) are summarized and discussed.
  
  
  CONCLUSIONS
  Effective adjunctive treatment for the symptoms of TD will depend on gaining a better understanding of the neurological changes induced by chronic dopamine D2 receptor antagonism from APs.
authors.affiliation: a Centre for Addiction and Mental Health (CAMH), Schizophrenia Division, Complex Mental Illness Program , 250 College Street, Toronto, Ontario M5T 1R8, Canada +1 416 535 8501 Ext. 34864 (Connie) ; +1 416 979 4292 ; gary.remington@camh.ca.
authors.forename: Jonathan Tomas
authors.initials: JT
authors.lastname: Lockwood
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D011618:Psychotic Disorders / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D015507:Drugs, Investigational; D017448:Receptors, Dopamine D2
keywords: Phase II; Phase III; antipsychotic side effects; investigational drugs; pharmacotherapy; tardive dyskinesia