Real-world effectiveness of mono- and combination therapies of mood stabilisers and antipsychotics in bipolar disorder: nationwide, within-individual study of 315 046 patients.
Level 3 - non-randomized controlled study
Nationwide observational cohort study using a within-individual design
PubMed 42057566 · doi:10.1192/bjp.2026.10636
What was done
A nationwide, population-based cohort study evaluated 315,046 adult patients (aged ≥20 years) with a primary diagnosis of bipolar disorder treated in psychiatric settings in Japan between April 2013 and March 2022, followed through May 2023 (median follow-up 7.1 years). Using a within-individual design and stratified Cox regression, the authors compared time to psychiatric hospitalisation across periods of mood stabiliser monotherapy, antipsychotic monotherapy, and combination regimens versus non-use or lithium monotherapy.
What was found
During follow-up, 83,621 patients (26.5%) were hospitalised. Compared with non-use of mood stabilisers, monotherapy reduced hospitalisation: lithium (adjusted hazard ratio [aHR] 0.67, 95% CI 0.66–0.68), valproate (aHR 0.71, 95% CI 0.70–0.73), lamotrigine (aHR 0.72, 95% CI 0.69–0.75), and carbamazepine (aHR 0.74, 95% CI 0.70–0.78). Antipsychotic monotherapies also reduced risk relative to non-use, including aripiprazole (aHR 0.73, 95% CI 0.70–0.75) and zotepine (aHR 0.74, 95% CI 0.69–0.79). Compared with lithium monotherapy, combination therapy further reduced hospitalisation risk when combining lithium with carbamazepine (aHR 0.73, 95% CI 0.64–0.83), zotepine (aHR 0.82, 95% CI 0.72–0.93), aripiprazole (aHR 0.87, 95% CI 0.82–0.92), or valproate (aHR 0.92, 95% CI 0.87–0.97).
Why it matters
This study provides large-scale, real-world evidence comparing specific monotherapies and combination regimens for bipolar disorder, demonstrating that select combination therapies offer incremental protection against psychiatric admission beyond lithium alone.
Limits
The analysis is observational and subject to potential time-varying confounding by indication or illness severity, despite the within-individual design. Outcomes were restricted to psychiatric hospitalisation rather than symptom severity, functional recovery, or adverse drug effects, and data were limited to administrative claims from a single country (Japan).
Cited by
- supports The anti-seizure medications lamotrigine, valproate, and carbamazepine are used to treat bipolar disorder.