Lithium’s decline and rising antipsychotic use spark concern
A 24-year study of 8,707 bipolar disorder inpatients in Germany, Austria, and Switzerland reveals significant shifts in prescription practices, with lithium use declining and second-generation antipsychotics (SGAs) becoming the mainstay treatment.
Published in the International Journal of Bipolar Disorders, the findings raise concerns about adherence to clinical guidelines and patient outcomes.
Key trends in bipolar disorder treatment
Analysing data from 1994–2017, researchers found lithium prescriptions dropped from 45% to 30%, stabilising after 2004. Meanwhile, SGAs like quetiapine and olanzapine surged, dominating treatment regimens by 2017. Antidepressants, despite limited evidence for efficacy in bipolar depression, were prescribed to over 60% of patients with depressive episodes. Lithium-treated patients received more medications overall (mean 5 vs. 4.75 drugs), suggesting complex cases or reluctance to prioritise lithium monotherapy.
Why are these trends worrying?
- Lithium’s unique benefits: Guidelines recommend lithium for its mood-stabilising, anti-suicidal, and neuroprotective effects. Its decline risks losing these benefits, particularly for high-risk patients.
- Antipsychotic risks: SGAs like quetiapine and olanzapine, while effective, carry metabolic side effects. Their long-term safety in bipolar management remains debated.
- Antidepressant overuse: High antidepressant prescriptions contradict guidelines warning of manic switches, especially without mood stabilisers like lithium.
Differences between lithium and non-lithium groups
- Lithium patients received more thyroid medications (21% vs. 16%), likely due to lithium’s side effects, but fewer anticonvulsants (16% vs. 38%).
- Non-lithium patients had higher rates of valproate (38%) and quetiapine (33%) use, alongside more antihypertensives and gastrointestinal drugs.
Implications for clinicians and policymakers
The study underscores a troubling disconnect between evidence-based guidelines and real-world practice. Factors driving lithium’s decline may include:
- Perceived safety concerns and intensive monitoring requirements.
- Marketing and ease of prescribing SGAs.
- Misconceptions about lithium’s tolerability.
Calls to action
Researchers urge initiatives to:
- Promote lithium’s unique advantages through clinician education.
- Reduce inappropriate antidepressant use in bipolar depression.
- Address polypharmacy risks, particularly in lithium-treated patients.
Conclusion
As SGAs reshape bipolar treatment, this study highlights the need to reconcile clinical practice with guidelines. Prioritising lithium where appropriate and curbing antidepressant overuse could improve patient outcomes. For clinicians, these findings reinforce the importance of balancing innovation with evidence-based care in managing this complex condition.
Greil, W., de Bardeci, M., Nievergelt, N. et al. Twenty-four years of prescription patterns in bipolar disorder inpatients with vs without lithium: a pharmacoepidemiological analysis of 8,707 cases in German-speaking countries. Int J Bipolar Disord 13, 3 (2025). https://doi.org/10.1186/s40345-025-00370-1