title: Extrapyramidal motor side-effects of first- and second-generation antipsychotic drugs.
abstract: BACKGROUND
  Second-generation antipsychotics have been thought to cause fewer extrapyramidal side-effects (EPS) than first-generation antipsychotics, but recent pragmatic trials have indicated equivalence.
  
  
  OBJECTIVE
  To determine whether second-generation antipsychotics had better outcomes in terms of EPS than first-generation drugs.
  
  
  METHODS
  We conducted an intention-to-treat, secondary analysis of data from an earlier randomised controlled trial (n = 227). A clinically significant difference was defined as double or half the symptoms in groups prescribed first- v. second-generation antipsychotics, represented by odds ratios greater than 2.0 (indicating advantage for first-generation drugs) or less than 0.5 (indicating advantage for the newer drugs). We also examined EPS in terms of symptoms emergent at 12 weeks and 52 weeks, and symptoms that had resolved at these time points.
  
  
  RESULTS
  At baseline those randomised to the first-generation antipsychotic group (n = 118) had similar EPS to the second-generation group (n = 109). Indications of resolved Parkinsonism (OR = 0.5) and akathisia (OR = 0.4) and increased tardive dyskinesia (OR = 2.2) in the second-generation drug group at 12 weeks were not statistically significant and the effects were not present by 52 weeks. Patients in the second-generation group were dramatically (30-fold) less likely to be prescribed adjunctive anticholinergic medication, despite equivalence in terms of EPS.
  
  
  CONCLUSIONS
  The expected improvement in EPS profiles for participants randomised to second-generation drugs was not found; the prognosis over 1 year of those in the first-generation arm was no worse in these terms. The place of careful prescription of first-generation drugs in contemporary practice remains to be defined, potentially improving clinical effectiveness and avoiding life-shortening metabolic disturbances in some patients currently treated with the narrow range of second-generation antipsychotics used in routine practice. This has educational implications because a generation of psychiatrists now has little or no experience with first-generation antipsychotic prescription.
authors.affiliation: Yale School of Medicine, New Haven, Connecticut, USA. michael.peluso@yale.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Peluso
authors.forename: Shôn W
authors.initials: SW
authors.lastname: Lewis
authors.forename: Thomas R E
authors.initials: TR
authors.lastname: Barnes
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017109:Akathisia, Drug-Induced / Q000209:etiology; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001480:Basal Ganglia Diseases / Q000139:chemically induced*; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D006801:Humans; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000139:chemically induced; D011379:Prognosis; D011618:Psychotic Disorders / Q000188:drug therapy; D012563:Schizophrenia, Paranoid / Q000188:drug therapy; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018680:Cholinergic Antagonists