title: Self-harm, Unintentional Injury, and Suicide in Bipolar Disorder During Maintenance Mood Stabilizer Treatment: A UK Population-Based Electronic Health Records Study.
abstract: Self-harm is a prominent cause of morbidity in patients with bipolar disorder and is strongly associated with suicide. There is evolving evidence that lithium use may reduce suicidal behavior, in addition to concerns that the use of anticonvulsants may increase self-harm. Information is limited about the effects of antipsychotics when used as mood stabilizer treatment. Rates of unintentional injury are poorly defined in bipolar disorder, and understanding drug associations with this outcome may shed light on mechanisms for lithium's potential antisuicidal properties through reduction in impulsive aggression.
  
  
  
  To compare rates of self-harm, unintentional injury, and suicide in patients with bipolar disorder who were prescribed lithium, valproate sodium, olanzapine, or quetiapine fumarate.
  
  
  
  This investigation was a propensity score (PS)-adjusted and PS-matched longitudinal cohort study in a nationally representative UK sample using electronic health records data collected between January 1, 1995, and December 31, 2013. Participants included all patients diagnosed as having bipolar disorder who were prescribed lithium, valproate, olanzapine, or quetiapine as maintenance mood stabilizer treatment.
  
  
  
  The primary outcome was any form of self-harm. Secondary outcomes were unintentional injury and suicide.
  
  
  
  Of the 14 396 individuals with a diagnosis of BPD, 6671 were included in the cohort, with 2148 prescribed lithium, 1670 prescribed valproate, 1477 prescribed olanzapine, and 1376 prescribed quetiapine as maintenance mood stabilizer treatment. Self-harm rates were lower in patients prescribed lithium (205; 95% CI, 175-241 per 10 000 person-years at risk [PYAR]) compared with those prescribed valproate (392; 95% CI, 334-460 per 10 000 PYAR), olanzapine (409; 95% CI, 345-483 per 10 000 PYAR), or quetiapine (582; 95% CI, 489-692 per 10 000 PYAR). This association was maintained after PS adjustment (hazard ratio [HR], 1.40; 95% CI, 1.12-1.74 for valproate, olanzapine, or quetiapine vs lithium) and PS matching (HR, 1.51; 95% CI, 1.21-1.88). After PS adjustment, unintentional injury rates were lower for lithium compared with valproate (HR, 1.32; 95% CI, 1.10-1.58) and quetiapine (HR, 1.34; 95% CI, 1.07-1.69) but not olanzapine. The suicide rate in the cohort was 14 (95% CI, 9-21) per 10 000 PYAR. Although this rate was lower in the lithium group than for other treatments, there were too few events to allow accurate estimates.
  
  
  
  Patients taking lithium had reduced self-harm and unintentional injury rates. This finding augments limited trial and smaller observational study results. It supports the hypothesis that lithium use reduces impulsive aggression in addition to stabilizing mood.
authors.affiliation: Division of Psychiatry, University College London, London, England.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Hayes
authors.affiliation: Division of Psychiatry, University College London, London, England.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pitman
authors.affiliation: Department of Primary Care and Population Health, University College London, London, England.
authors.forename: Louise
authors.initials: L
authors.lastname: Marston
authors.affiliation: Department of Primary Care and Population Health, University College London, London, England.
authors.forename: Kate
authors.initials: K
authors.lastname: Walters
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, England.
authors.forename: John R
authors.initials: JR
authors.lastname: Geddes
authors.affiliation: Division of Psychiatry, University College London, London, England.
authors.forename: Michael
authors.initials: M
authors.lastname: King
authors.affiliation: Division of Psychiatry, University College London, London, England.
authors.forename: David P J
authors.initials: DP
authors.lastname: Osborn
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000453:epidemiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D057286:Electronic Health Records; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000009:adverse effects* / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D057216:Propensity Score; D000069348:Quetiapine Fumarate / Q000009:adverse effects* / Q000627:therapeutic use*; D016728:Self-Injurious Behavior / Q000453:epidemiology*; D013405:Suicide / Q000706:statistics & numerical data*; D016896:Treatment Outcome; D006113:United Kingdom; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use*; D014947:Wounds and Injuries / Q000453:epidemiology*
chemical_list: D018692:Antimanic Agents; D001569:Benzodiazepines; D016651:Lithium Carbonate; D000069348:Quetiapine Fumarate; D014635:Valproic Acid; D000077152:Olanzapine