title: The Harms of Antipsychotic Drugs: Evidence from Key Studies.
abstract: This safety assessment provides a detailed analysis of key studies and focuses on the six most widely used antipsychotic drugs. Lines of evidence include mechanisms of action, short-term treatment of psychosis, relapse prevention, early intervention in schizophrenia, long-term comparisons between first- and second-generation agents, and flexible treatment algorithms. Despite the diversity of study settings, several common features were seen. All the agents obstruct normal signaling through widely dispersed dopamine D2receptors. Treatment failure or psychosis relapse was the most frequent outcome in most key studies, ranging from 38 to 93%. High discontinuation rates caused most trials to fail to demonstrate a substantial treatment benefit, or difference from an active comparator. Assessment of harm to the extrapyramidal motor system was confounded because of extensive neurological impairment from previous antipsychotic drug treatment measured at baseline, abrupt discontinuation effects, and high rates of concomitant medications to manage drug adverse effects. Claims that second-generation antipsychotic drugs have safety advantages over classical neuroleptic drugs and prevent relapse were not supported in these key studies. The extent of injury to and impairment of multiple body systems caused by antipsychotic drugs shows the need for a scientific, clinical, and regulatory reappraisal of the appropriate use of these agents.
authors.affiliation: Institute for Safe Medication Practices, 101 N. Columbus St, Suite 410, Alexandria, VA, 22314, USA. tmoore@ismp.org.|Department of Epidemiology and Biostatistics, George Washington University Milken Institute School of Public Health, Washington, DC, USA. tmoore@ismp.org.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Moore
authors.affiliation: Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Curt D
authors.initials: CD
authors.lastname: Furberg
mesh_terms: D000465:Algorithms; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D011618:Psychotic Disorders / Q000188:drug therapy*; D012008:Recurrence; D012107:Research Design; D012559:Schizophrenia / Q000188:drug therapy*; D017211:Treatment Failure
chemical_list: D014150:Antipsychotic Agents