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Review

Future Pharmacotherapy for Bipolar Disorders: Emerging Trends and Personalized Approaches

1
Unit of Psychiatry, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
2
Department of Neurosciences, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
3
Unit of Medical Genetics, Department of Laboratory Medicine, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy
4
Spine Surgery Department, Bambino Gesù Children’s Hospital IRCCS, 00168 Rome, Italy
5
Section of Internal Medicine and Thromboembolic Diseases, Department of Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
6
Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
7
Unit of Internal Medicine, Cristo Re Hospital, 00167 Rome, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Future Pharmacol. 2025, 5(3), 42; https://doi.org/10.3390/futurepharmacol5030042 (registering DOI)
Submission received: 3 July 2025 / Revised: 25 July 2025 / Accepted: 29 July 2025 / Published: 4 August 2025

Abstract

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry.
Keywords: bipolar disorder; pharmacotherapy; digital therapeutics; precision psychiatry bipolar disorder; pharmacotherapy; digital therapeutics; precision psychiatry

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MDPI and ACS Style

Marano, G.; Lisci, F.M.; Boggio, G.; Marzo, E.M.; Abate, F.; Sfratta, G.; Traversi, G.; Mazza, O.; Pola, R.; Sani, G.; et al. Future Pharmacotherapy for Bipolar Disorders: Emerging Trends and Personalized Approaches. Future Pharmacol. 2025, 5, 42. https://doi.org/10.3390/futurepharmacol5030042

AMA Style

Marano G, Lisci FM, Boggio G, Marzo EM, Abate F, Sfratta G, Traversi G, Mazza O, Pola R, Sani G, et al. Future Pharmacotherapy for Bipolar Disorders: Emerging Trends and Personalized Approaches. Future Pharmacology. 2025; 5(3):42. https://doi.org/10.3390/futurepharmacol5030042

Chicago/Turabian Style

Marano, Giuseppe, Francesco Maria Lisci, Gianluca Boggio, Ester Maria Marzo, Francesca Abate, Greta Sfratta, Gianandrea Traversi, Osvaldo Mazza, Roberto Pola, Gabriele Sani, and et al. 2025. "Future Pharmacotherapy for Bipolar Disorders: Emerging Trends and Personalized Approaches" Future Pharmacology 5, no. 3: 42. https://doi.org/10.3390/futurepharmacol5030042

APA Style

Marano, G., Lisci, F. M., Boggio, G., Marzo, E. M., Abate, F., Sfratta, G., Traversi, G., Mazza, O., Pola, R., Sani, G., Gaetani, E., & Mazza, M. (2025). Future Pharmacotherapy for Bipolar Disorders: Emerging Trends and Personalized Approaches. Future Pharmacology, 5(3), 42. https://doi.org/10.3390/futurepharmacol5030042

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