Extrapyramidal motor side-effects of first- and second-generation antipsychotic drugs.

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. AIMS To determine whether second-generation antipsychotics had better outcomes in terms of EPS than first-generation drugs. METHOD 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.

[1]  T. Barnes,et al.  Attitudes to atypical and conventional antipsychotic drug treatment in clinicians participating in the cutlass study , 2005, International journal of psychiatry in clinical practice.

[2]  W. Glazer,et al.  Extrapyramidal side effects, tardive dyskinesia, and the concept of atypicality. , 2000, The Journal of clinical psychiatry.

[3]  R. Rosenheck.  Open forum: effectiveness versus efficacy of second-generation antipsychotics: haloperidol without anticholinergics as a comparator. , 2005, Psychiatric services.

[4]  J. J. Stolker,et al.  Haloperidol dose when used as active comparator in randomized controlled trials with atypical antipsychotics in schizophrenia: comparison with officially recommended doses. , 2006, The Journal of clinical psychiatry.

[5]  B. Bégaud,et al.  Antipsychotic prescribing trends: a review of pharmaco‐epidemiological studies , 2010, Acta psychiatrica Scandinavica.

[6]  Peter B. Jones,et al.  Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). , 2006, Archives of general psychiatry.

[7]  J. Lieberman,et al.  Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. , 2005, The New England journal of medicine.

[8]  E. Faerstein,et al.  A DICTIONARY OF EPIDEMIOLOGY , 2016 .

[9]  E. Weiss,et al.  Second-Generation Antipsychotics , 2006, Drug safety.

[10]  E. Rüther,et al.  Effect of Anticholinergics on Tardive Dyskinesia , 1984, British Journal of Psychiatry.

[11]  A. Bravo-Mehmedbašić.  Risperidone in the treatment of schizophrenia. , 2011, Medicinski arhiv.

[12]  K. Fletcher,et al.  Neuroleptic-related dyskinesias in children and adolescents. , 2001, The Journal of clinical psychiatry.

[13]  Miquel Porta,et al.  A Dictionary of Epidemiology , 2008 .

[14]  S. Leucht,et al.  New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis , 2003, The Lancet.

[15]  P. Grant,et al.  Prevalence of movement disorders in adolescent patients with schizophrenia and in relationship to predominantly atypical antipsychotic treatment , 2006, European Child & Adolescent Psychiatry.

[16]  [Atypical antipsychotic drugs]. , 2000, Nederlands tijdschrift voor geneeskunde.

[17]  T. Barnes.  Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology , 2011, Journal of psychopharmacology.

[18]  N. Moore,et al.  The behavioral pharmacology of olanzapine, a novel "atypical" antipsychotic agent. , 1992, The Journal of pharmacology and experimental therapeutics.

[19]  Jeffrey A. Lieberman,et al.  Extrapyramidal side-effects of antipsychotics in a randomised trial , 2008, British Journal of Psychiatry.

[20]  N Freemantle,et al.  Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis , 2000, BMJ : British Medical Journal.

[21]  H. Klawans,et al.  Effect of cholinergic and anticholinergic agents on tardive dyskinesia 1 , 1974, Journal of neurology, neurosurgery, and psychiatry.

[22]  T. Barnes,et al.  The Barnes Akathisia Rating Scale–Revisited , 2003, Journal of psychopharmacology.

[23]  S. Normand,et al.  Atypical antipsychotics and parkinsonism. , 2005, Archives of internal medicine.

[24]  G. Tollefson,et al.  Negative symptoms: a path analytic approach to a double-blind, placebo- and haloperidol-controlled clinical trial with olanzapine. , 1997, American Journal of Psychiatry.

[25]  S. Potkin,et al.  Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. , 2003, Archives of general psychiatry.

[26]  M Greaves,et al.  Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study. , 2006, Health technology assessment.

[27]  June Corwin,et al.  Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial. , 2003, JAMA.

[28]  J. Kane.  Tardive dyskinesia rates with atypical antipsychotics in adults: prevalence and incidence. , 2004, The Journal of clinical psychiatry.

[29]  M. Mortimer.  Another triumph of hope over experience ? , 2005 .

[30]  W T Carpenter,et al.  The Quality of Life Scale: an instrument for rating the schizophrenic deficit syndrome. , 1984, Schizophrenia bulletin.

[31]  S. Potkin,et al.  Ziprasidone 80 mg/day and 160 mg/day in the Acute Exacerbation of Schizophrenia and Schizoaffective Disorder: A 6-Week Placebo-Controlled Trial , 1999, Neuropsychopharmacology.

[32]  R. Murray,et al.  Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment. , 2006, Health technology assessment.

[33]  S. Caroff,et al.  Movement disorders associated with atypical antipsychotic drugs. , 2002, The Journal of clinical psychiatry.

[34]  L. Kazis,et al.  Adjunctive use of atypical antipsychotics and anticholinergic drugs among patients with schizophrenia , 2005, Journal of clinical pharmacy and therapeutics.

[35]  L. Arvanitis,et al.  Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: A comparison with haloperidol and placebo , 1997, Biological Psychiatry.

[36]  G. Simpson,et al.  A RATING SCALE FOR EXTRAPYRAMIDAL SIDE EFFECTS , 1970, Acta psychiatrica Scandinavica. Supplementum.