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Cited by 121Bipolar Disorder and TreatmentSuicide and Self-Harm StudiesPersonality Disorders and Psychopathology

Self-harm, Unintentional Injury, and Suicide in Bipolar Disorder During Maintenance Mood Stabilizer Treatment: A UK Population-Based Electronic Health Records Study

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Hayes, Joseph F., Pitman, Alexandra, Marston, Louise, Walters, Kate, Geddes, John R., King, Michael, Osborn, David P. J.·2016·JAMA Psychiatry
DOI 10.1001/jamapsychiatry.2016.0432
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Abstract

IMPORTANCE: 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. OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: The primary outcome was any form of self-harm. Secondary outcomes were unintentional injury and suicide. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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.

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  • Large numbers in population databases make it possible to evaluate differences in rates of rare events such as less common side effects or suicide.

    “These large numbers make it possible to evaluate differences in rates of rare events such as less common side effects or suicide.361, 362”

    From Canadian Network for Mood and Anxiety Treatments ( <scp>CANMAT</scp> ) and International Society for Bipolar Disorders ( <scp>ISBD</scp> ) 2018 guidelines for the management of patients with bipolar disorder (2018) · cites this paper as [362]

    The Setting section describes a database of more than 11 million people, but the Suicide and Discussion sections say the study had too few suicide deaths to evaluate differences in rates between drugs. The paper therefore contradicts the claim’s suicide example; it does not examine less common side effects. (LLM, conf=0.87)

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  • Most of the data supporting lithium's utility in preventing suicide related outcomes derives from observational studies of patients followed clinically with lithium, and some studies have reported conflicting data.

    “However, most of the data supporting its utility in preventing suicide related outcomes derives from observational studies of patients followed clinically with lithium 292,293 and some studies have reported conflicting data 294 .”

    From Suicide and suicide risk (2019) · cites this paper as [294]

  • These results are slightly lower than those from meta-analyses in the existing literature, but are consistent with population-based samples.

    “These results are slightly lower than those from meta-analyses in the existing literature,7,33 but are consistent with population-based samples”

    From Mortality gap for people with bipolar disorder and schizophrenia: UK-based cohort study 2000–2014 (2017) · cites this paper as [7]

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Research works printed but not linked: 3

  1. [12]12. Baldessarini RJ, Tondo L, Davis P, Pompili M, Goodwin FK, Hennen J. Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review [published correction appears in Bipolar Disord. 2007;9(3):314]. Bipolar Disord. 2006;8(5, pt 2):625-639.
  2. [13]13. Schou M. The effect of prophylactic lithium treatment on mortality and suicidal behavior: a review for clinicians. J Affect Disord. 1998;50(2-3): 253-259.
  3. [34]34. Blak B, Thompson M, Bourke A. National representativeness and data quality of The Health Improvement Network (THIN) database of primary care information for epidemiological research. Paper presented at: 9th Annual Conference of the UK Federation of Primary Care Research Organisations; November 27, 2006; Liverpool, England.

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Authors
Hayes, J. F., Pitman, A., Marston, L., Walters, K., Geddes, J. R., King, M., & Osborn, D. P. J.
Affiliations
  • University College London (GB)
  • University of Oxford (GB)
Corresponding author
Hayes, Joseph F.
ORCID
Venue
JAMA Psychiatry
Publisher
American Medical Association (AMA)
Published
2016-06-01
Volume
73
Issue
6
Pages
630
ISSN
2168-622X (ISSN-L)
DOI
10.1001/jamapsychiatry.2016.0432
OpenAlex
W2357591654
Cited by
121
References
69
Citations by year
2026: 5 · 2025: 13 · 2024: 13 · 2023: 13 · 2022: 9 · 2021: 17 · 2020: 9 · 2019: 14 · 2018: 14 · 2017: 11 · 2016: 2 · 2015: 1
FWCI
12.14
Type
journal article
Language
en
Open access
Locations
  • JAMA Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • National Institute for Health and Care Research (NF-SI-0611-10210)
  • Medical Research Council (MR/L501487/1, MR/K021362/1)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
  • Social Sciences › Psychology › Clinical Psychology › Personality Disorders and Psychopathology
Keywords
bipolar disorder, self-harm, suicide, unintentional injuries, mood stabilizers, lithium, valproic acid, olanzapine, quetiapine, antipsychotic drugs, antiepileptic drugs, maintenance therapy, drug safety, suicide risk, impulsivity, aggression, propensity score matching
MeSH terms
Quetiapine Fumarate, Olanzapine, Adult, Benzodiazepines, Bipolar Disorder, Cross-Sectional Studies, Female, United Kingdom, Humans, Longitudinal Studies, Male, Middle Aged, Suicide, Valproic Acid, Wounds and Injuries, Cohort Studies, Lithium Carbonate, Self-Injurious Behavior, Treatment Outcome, Antimanic Agents, Propensity Score, Electronic Health Records

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