title: Reducing the rehospitalization risk after a manic episode: A population based cohort study of lithium, valproate, olanzapine, quetiapine and aripiprazole in monotherapy and combinations.
abstract: Data on real-world rehospitalization risks in patients using different drugs and combination therapies for relapse prevention after a manic episode is limited.
  
  
  
  We conducted a nationwide population based cohort study using data from Swedish national registers. Swedish residents aged 18-75 years who were hospitalized for a manic episode between July 1, 2006 and December 2, 2014 were included. Prescription fills of lithium, valproate, olanzapine, quetiapine and aripiprazole were recorded throughout the first four weeks after hospital discharge, after which the patients were followed for up to one year. General and treatment specific rehospitalization risks were determined and results were adjusted for clinical and sociodemographic factors.
  
  
  
  The study included follow-up data from 6 502 hospitalizations for mania. Pharmacologic relapse prevention was used after 78% of these hospitalizations. Monotherapies and combination therapies were equally common. The average one-year rehospitalization risk for patients who did versus did not initiate prophylactic treatment was 39% and 46%, respectively. The lowest rehospitalization risks were seen in patients on combination therapy with olanzapine and valproate or olanzapine and lithium, experiencing one year rehospitalization risks of 32% and 34% (adjusted hazard ratios 0.76 (95% confidence interval [CI] 0.62-0.93) and 0.83 (95% CI 0.70-0.98), compared to lithium monotherapy).
  
  
  
  Register data does not provide information on all clinical parameters affecting treatment choices.
  
  
  
  One-year rehospitalization rates after a manic episode are considerable also for patients who initiate prophylactic treatment. Combination therapies including olanzapine and a classic mood-stabilizer may be beneficial for reducing rehospitalization risks after a manic episode.
authors.affiliation: Centre for Pharmacoepidemiology (CPE), Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. Electronic address: louise.wingard@ki.se.
authors.forename: Louise
authors.initials: L
authors.lastname: Wingård
authors.affiliation: Centre for Pharmacoepidemiology (CPE), Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Bodén
authors.affiliation: Centre for Pharmacoepidemiology (CPE), Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Brandt
authors.affiliation: Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
authors.affiliation: Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Tanskanen
authors.affiliation: Centre for Pharmacoepidemiology (CPE), Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Helle
authors.initials: H
authors.lastname: Kieler
authors.affiliation: Centre for Pharmacoepidemiology (CPE), Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Morten
authors.initials: M
authors.lastname: Andersen
authors.affiliation: Centre for Pharmacoepidemiology (CPE), Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Reutfors
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018692:Antimanic Agents / Q000627:therapeutic use; D000068180:Aripiprazole / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D000069348:Quetiapine Fumarate / Q000627:therapeutic use*; D012042:Registries; D055502:Secondary Prevention / Q000379:methods; D014635:Valproic Acid / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D014635:Valproic Acid; D000068180:Aripiprazole; D000077152:Olanzapine
keywords: Anticonvulsants; Bipolar disorder; Cohort study; Lithium; Treatment outcome