Real-world effectiveness of mood stabilizers on self-harm and suicide attempts in patients with bipolar disorder: A 2-year mirror-image study

Abstract

Background: Bipolar disorder (BD) is associated with a high incidence of intentional self-harm and suicide attempts (SH/SA), however the effectiveness of mood-stabilizers on SH/SA remains controversial. We aimed to evaluate the real-world effectiveness of mood-stabilizers (lithium, lamotrigine, valproate, olanzapine, risperidone, aripiprazole, clozapine, and quetiapine) on SH/SA in patients with BD. Methods: A two-year mirror-image design (traditional and reverse) was applied using data from nationwide Danish healthcare registers. Results: In the traditional mirror-image design, treatment initiation with valproate was associated with a decreased SH/SA-incidence in all patients with BD (from 18 to 11 events/1000 person years (PYs), P = .03). In treatment-naïve patients with BD, lithium initiation was associated with a decreased SH/SA-incidence (from 12 to 7 incidents per 1000 PYs, P < .01). In the reverse mirror-image design, lamotrigine discontinuation was associated with a decreased SH/SA-incidence for all patients (from 27 to 14 incidents per 1000 PYs, P = .03). In a secondary analysis, not restricted to patients with BD, lithium initiation was associated with a decreased SH/SA-incidence (from 16 to 11 events/1000 PYs, P < .01) and lithium discontinuation with an increased SH/SA-incidence in males (from 6 to 10 incidents per 1000 PYs, P = .03). Limitations: Time-variant confounders may influence the results and may yield false positive (mimicking either a harmful or a protective effect) or false negative findings (no effect). Conclusion: The present findings suggest that lithium and valproate may protect against self-harm and suicide attempts in bipolar disorder.

Keywords

• Pharmacoepidemiology
• Bipolar disorder
• Self-injurious behaviour
• Suicide
• Antimanic agents