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Review
. 2025 Aug 30;406(10506):963-978.
doi: 10.1016/S0140-6736(25)01140-7. Epub 2025 Jul 22.

Bipolar disorder

Affiliations
Review

Bipolar disorder

Balwinder Singh et al. Lancet. .

Abstract

The hallmark of bipolar disorder is hypomania or mania, and the predominant phase of illness is depression. Affecting approximately 40 million individuals worldwide, bipolar disorder is associated with a substantial psychosocial, medical, and financial burden and increased mortality from suicide and other causes. Diagnosis can be challenging due to symptom overlap with attention-deficit hyperactivity disorder, major depressive disorder, psychotic spectrum disorders, and personality disorders, which often leads to a delay in diagnosis. Recent advancements in understanding disease risk and pathophysiology have identified multigene risk and possible infectious and mitochondrial causes. Treatment approaches include pharmacotherapy, psychotherapy, and lifestyle modifications, which should always be patient-centred and aligned with individual goals and priorities. Future directions for bipolar disorder care include increasing the availability of psychosocial interventions aimed at self-management, addressing treatment-resistant bipolar depression, deepening the understanding of pathophysiology, and exploring novel interventions, such as ketamine, esketamine, other rapid-acting antidepressants, and various neuromodulation approaches.

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Conflict of interest statement

Declaration of interests BS has received research grant support from Mayo Clinic, the National Network of Depression Centers, Breakthrough Discoveries for Thriving with Bipolar Disorder (BD2), and the National Institutes of Health. He is a KL2 Mentored Career Development Program scholar, supported by Clinical and Translational Science Award Grant Number KL2TR002379 from the National Center for Advancing Translational Science. He has received honoraria (to the Mayo Clinic) from Elsevier for editing a clinical overview on treatment-resistant depression. HAS has received honoraria from or consulted for Intracellular Therapies, Physician Postgraduate Press, Medscape and WebMD, Mediflix, and Clinical Education Alliance. AS has received support from an Academic Scholars Award, Sunnybrook Health Sciences Centre, and the University of Toronto, and has received honoraria from AbbVie, Lundbeck, and Otsuka. KEB has received honoraria from BD2 and as a scientific advisory board member for Merck, Alto Neuroscience, and Suven Life Sciences. MAF has received grant support from Assurex Health, the Mayo Foundation, and BD2, has received CME travel support and honoraria from Carnot Laboratories and American Physician Institute, and financial interest in, stock ownership in, or royalties from Chymia. All other authors declare no competing interests.

References

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