title: Lifetime use of antipsychotic medication and its relation to change of verbal learning and memory in midlife schizophrenia - An observational 9-year follow-up study.
abstract: BACKGROUND
  The association between the course of cognition and long-term antipsychotic medication in schizophrenia remains unclear. We analysed the association between cumulative lifetime antipsychotic medication dose and change of verbal learning and memory during a 9-year follow-up.
  
  
  METHODS
  Forty schizophrenia subjects and 73 controls from the Northern Finland Birth Cohort 1966 were assessed by California Verbal Learning Test (CVLT) at the ages of 34 and 43 years. Data on the lifetime antipsychotic doses in chlorpromazine equivalents were collected. The association between antipsychotic dose-years and baseline performance and change in CVLT was analysed, controlling for baseline performance, gender, age of onset and severity of illness.
  
  
  RESULTS
  Higher antipsychotic dose-years by baseline were significantly associated with poorer baseline performance in several dimensions of verbal learning and memory, and with a larger decrease in short-delay free recall during the follow-up (p=0.031). Higher antipsychotic dose-years during the follow-up were associated with a larger decrease of immediate free recall of trials 1-5 during the follow-up (p=0.039). Compared to controls, decline was greater in some CVLT variables among those using high-doses, but not among those using low-doses.
  
  
  CONCLUSIONS
  This is the first report of an association between cumulative lifetime antipsychotic use and change in cognition in a long-term naturalistic follow-up. The use of high doses of antipsychotics may be associated with a decrease in verbal learning and memory in schizophrenia years after illness onset. The results do not support the view that antipsychotics in general prevent cognitive decline or promote cognitive recovery in schizophrenia.
authors.affiliation: University of Oulu, Institute of Clinical Medicine, Department of Psychiatry, P.O. Box 5000, 90014 University of Oulu, Finland; Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Finland. Electronic address: anja.husa@student.oulu.fi.
authors.forename: Anja P
authors.initials: AP
authors.lastname: Husa
authors.affiliation: University of Oulu, Institute of Clinical Medicine, Department of Psychiatry, P.O. Box 5000, 90014 University of Oulu, Finland.
authors.forename: Irina
authors.initials: I
authors.lastname: Rannikko
authors.affiliation: University of Oulu, Institute of Clinical Medicine, Department of Psychiatry, P.O. Box 5000, 90014 University of Oulu, Finland; Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Finland; Oulu University Hospital, Department of Psychiatry, P.O. Box 26, 90029 OYS, Finland.
authors.forename: Jani
authors.initials: J
authors.lastname: Moilanen
authors.affiliation: University of Oulu, Institute of Clinical Medicine, Department of Psychiatry, P.O. Box 5000, 90014 University of Oulu, Finland; Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Finland; Oulu University Hospital, Department of Psychiatry, P.O. Box 26, 90029 OYS, Finland; Oulu University Hospital, Department of Diagnostic Radiology, P.O. Box 50, 90029 OYS, Finland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Haapea
authors.affiliation: University of Cambridge, Department of Psychiatry, Box 189 Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; University of Cambridge, Behavioural and Clinical Neuroscience Institute, Herchel Smith Building, Forvie Site, Cambridge Biomedical Campus, Cambridge CB2 0SZ, United Kingdom.
authors.forename: Graham K
authors.initials: GK
authors.lastname: Murray
authors.affiliation: University of Cambridge, Department of Psychiatry, Box 189 Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Cambridge Cognition Ltd, Tunbridge Court, Bottisham, Cambridge, United Kingdom.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Barnett
authors.affiliation: University of Cambridge, Department of Psychiatry, Box 189 Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jones
authors.affiliation: University of Oulu, Institute of Clinical Medicine, Department of Psychiatry, P.O. Box 5000, 90014 University of Oulu, Finland; Oulu University Hospital, Department of Psychiatry, P.O. Box 26, 90029 OYS, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Isohanni
authors.affiliation: Department of Psychiatry, Institute of Clinical Medicine, University of Helsinki, P.O. Box 22, 00014 Helsinki, Finland; Department of Psychiatry, Helsinki University Hospital, P.O. Box 590, FIN-00029 HUS, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Koponen
authors.affiliation: University of Oulu, Institute of Clinical Medicine, Department of Psychiatry, P.O. Box 5000, 90014 University of Oulu, Finland; Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Finland; Oulu University Hospital, Department of Psychiatry, P.O. Box 26, 90029 OYS, Finland; University of Oulu, Institute of Health Sciences, P.O. Box 5000, 90014 Oulu, Finland.
authors.forename: Jouko
authors.initials: J
authors.lastname: Miettunen
authors.affiliation: University of Oulu, Institute of Clinical Medicine, Department of Psychiatry, P.O. Box 5000, 90014 University of Oulu, Finland; Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Finland; Oulu University Hospital, Department of Psychiatry, P.O. Box 26, 90029 OYS, Finland; University of Oulu, Institute of Health Sciences, P.O. Box 5000, 90014 Oulu, Finland.
authors.forename: Erika
authors.initials: E
authors.lastname: Jääskeläinen
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002746:Chlorpromazine / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects*; D009483:Neuropsychological Tests; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013067:Speech Perception / Q000187:drug effects*; D014706:Verbal Learning / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D002746:Chlorpromazine
keywords: California Verbal Learning Test; Cognition; Follow-up; Longitudinal; Psychosis; Treatment