Extrapyramidal motor side-effects of first- and second-generation antipsychotic drugs. 2012

Michael J Peluso, and Shôn W Lewis, and Thomas R E Barnes, and Peter B Jones
Yale School of Medicine, New Haven, Connecticut, USA. michael.peluso@yale.edu

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.

UI MeSH Term Description Entries
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D011618 Psychotic Disorders Disorders in which there is a loss of ego boundaries or a gross impairment in reality testing with delusions or prominent hallucinations. (From DSM-IV, 1994) Psychoses,Psychosis, Brief Reactive,Schizoaffective Disorder,Schizophreniform Disorders,Psychosis,Brief Reactive Psychoses,Brief Reactive Psychosis,Disorder, Psychotic,Disorder, Schizoaffective,Disorder, Schizophreniform,Disorders, Psychotic,Disorders, Schizoaffective,Disorders, Schizophreniform,Psychoses, Brief Reactive,Psychotic Disorder,Reactive Psychoses, Brief,Reactive Psychosis, Brief,Schizoaffective Disorders,Schizophreniform Disorder
D004409 Dyskinesia, Drug-Induced Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199) Dyskinesia, Medication-Induced,Medication-Induced Dyskinesia,Drug-Induced Dyskinesia,Drug-Induced Dyskinesias,Dyskinesia, Drug Induced,Dyskinesia, Medication Induced,Dyskinesias, Drug-Induced,Dyskinesias, Medication-Induced,Medication Induced Dyskinesia,Medication-Induced Dyskinesias
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D001480 Basal Ganglia Diseases Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA. Extrapyramidal Disorders,Basal Ganglia Disorders,Lenticulostriate Disorders,Basal Ganglia Disease,Basal Ganglia Disorder,Extrapyramidal Disorder,Lenticulostriate Disorder
D012563 Schizophrenia, Paranoid A chronic form of schizophrenia characterized primarily by the presence of persecutory or grandiose delusions, often associated with hallucination. Delusional Disorder,Paranoid Schizophrenia,Delusional Disorders,Disorder, Delusional,Disorders, Delusional,Paranoid Schizophrenias,Schizophrenias, Paranoid

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