Self-harm, accidental injury, and suicide in bipolar disorder during maintenance mood stabilizer treatment: a UK population-based electronic health records study

Journal article

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 may reduce suicidal behavior, and concerns that anticonvulsants may increase self-harm. There is limited information about the effects of antipsychotics when used as mood stabilizer treatment. Rates of accidental injury are poorly defined in bipolar disorder, and understanding drug associations with this outcome may shed light on mechanisms for lithium’s potential anti-suicidal properties through reduction in impulsive aggression.

Objective

To compare rates of self-harm, accidental injury, and suicide in patients with bipolar disorder prescribed lithium, valproate, olanzapine or quetiapine.

Design

A propensity score adjusted and matched longitudinal cohort study in a nationally representative United Kingdom sample.

Setting

Electronic health record data collected January 1 1995 to December 31 2013

Participants

All patients diagnosed with bipolar disorder prescribed lithium (N=2148), valproate (N=1670), olanzapine (N=1477), or quetiapine (N=1376) as maintenance mood stabilizer treatment.

Main outcomes and measures

The primary outcome was any form of self-harm. Secondary outcomes were accidental injury and suicide.

Results

Self-harm rates were lower in patients prescribed lithium (205 per 10,000 person years at risk [PYAR]; 95%CI [confidence interval] 175-241) compared with those prescribed valproate (392 per 10,000 PYAR; 95%CI 334-460), olanzapine (409 per 10,000 PYAR; 95%CI 345-483) or quetiapine (582 per 10,000 PYAR; 95%CI 489-692). This relationship was maintained after propensity score adjustment (valproate, olanzapine or quetiapine versus lithium; hazard ratio [HR] 1.40; 95%CI 1.12-1.74) and matching (HR 1.51; 95%CI 1.21-1.88). After propensity score adjustment, accidental injury rates were lower in lithium compared to 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 per 10,000 PYAR (95%CI 9-21). Although this 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 accidental injury rates. This finding augments limited trial and smaller observational study results. It supports the hypothesis that lithium reduces impulsive aggression as well as stabilizing mood.

Authors: Hayes, J; Pitman, A; Marston, L; Walters, K; Geddes, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Medical Association
• Journal: JAMA Psychiatry
• Volume: 73
• Issue: 6
• Pages: 630-637
• Publication date: 2016-07-03
• Acceptance date: 2016-02-15
• DOI: 10.1001/jamapsychiatry.2016.0432
• EISSN: 2168-6238
• ISSN: 2168-622X