title: Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study.
abstract: OBJECTIVE
  To investigate the association between antidepressant therapy and the later onset of mania/bipolar disorder.
  
  
  METHODS
  Retrospective cohort study using an anonymised electronic health record case register.
  
  
  METHODS
  South London and Maudsley National Health Service (NHS) Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK.
  
  
  METHODS
  21,012 adults presenting to SLaM between 1 April 2006 and 31 March 2013 with unipolar depression.
  
  
  METHODS
  Prior antidepressant therapy recorded in electronic health records.
  
  
  METHODS
  Time to subsequent diagnosis of mania or bipolar disorder from date of diagnosis of unipolar depression, censored at 31 March 2014.
  
  
  METHODS
  Multivariable Cox regression analysis with age and gender as covariates.
  
  
  RESULTS
  The overall incidence rate of mania/bipolar disorder was 10.9 per 1000 person-years. The peak incidence of mania/bipolar disorder incidence was seen in patients aged between 26 and 35 years (12.3 per 1000 person-years). Prior antidepressant treatment was associated with an increased incidence of mania/bipolar disorder ranging from 13.1 to 19.1 per 1000 person-years. Multivariable analysis indicated a significant association with selective serotonin reuptake inhibitors (HR 1.34, 95% CI 1.18 to 1.52) and venlafaxine (1.35, 1.07 to 1.70).
  
  
  CONCLUSIONS
  In people with unipolar depression, antidepressant treatment is associated with an increased risk of subsequent mania/bipolar disorder. These findings highlight the importance of considering risk factors for mania when treating people with depression.
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
authors.forename: Rashmi
authors.identifier: http://orcid.org/0000-0002-9259-8788
authors.initials: R
authors.lastname: Patel
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.affiliation: Biomedical Research Centre Nucleus, South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Shetty
authors.affiliation: Biomedical Research Centre Nucleus, South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Broadbent
authors.affiliation: Department of Psychological Medicine, King's College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Stewart
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Taylor
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000453:epidemiology / Q000523:psychology; D003863:Depression / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D004334:Drug Administration Schedule; D057286:Electronic Health Records; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology; D000069470:Venlafaxine Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride
keywords: CRIS; SSRI; antidepressant induced mania; electronic health records; manic switch; venlafaxine