Approximately 40 % of patients with bipolar disorder experience mixed episodes, defined as a manic state with depressive features, or manic symptoms in a patient with bipolar depression. Compared with bipolar patients without mixed features, patients with bipolar mixed states generally have more severe symptomatology, more lifetime episodes of illness, worse clinical outcomes and higher rates of comorbidities, and thus present a significant clinical challenge. Most clinical trials have investigated second-generation neuroleptic monotherapy, monotherapy with anticonvulsants or lithium, combination therapy, and electroconvulsive therapy (ECT). Neuroleptic drugs are often used alone or in combination with anticonvulsants or lithium for preventive treatment, and ECT is an effective treatment for mixed manic episodes in situations where medication fails or cannot be used. Common antidepressants have been shown to worsen mania symptoms during mixed episodes without necessarily improving depressive symptoms; thus, they are not recommended during mixed episodes. A greater understanding of pathophysiological processes in bipolar disorder is now required to provide a more accurate diagnosis and new personalised treatment approaches. Targeted, specific treatments developed through a greater understanding of bipolar disorder pathophysiology, capable of affecting the underlying disease processes, could well prove to be more effective, faster acting, and better tolerated than existing therapies, therefore providing better outcomes for individuals affected by bipolar disorder. Until such time as targeted agents are available, second-generation neuroleptics are emerging as the treatment of choice in the management of mixed states in bipolar disorder.
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The authors would like to thank Sheridan Henness, PhD, of Springer Healthcare Communications, for medical writing assistance, including drafting of the manuscript, English editing of the ‘Expert Opinion and Practical Guidance’ section, and assistance with post-submission revisions. This assistance was funded by Lundbeck, Italy.
Medical writing assistance was funded by Lundbeck, Italy.
Conflicts of interest
The authors declare the following conflicts of interest. Andrea Fagiolini received research grants and/or honoraria as a consultant to and/or participant on advisory boards from Angelini, Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Lundbeck, Novartis, Otsuka, Pfizer, Boehringer Ingelheim, Takeda and Roche.
Allan H. Young is employed by King’s College London, is an Honorary Consultant to the South London and Maudsley NHS Foundation Trust (SLaM), has received fees for paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders, and has no share holdings in pharmaceutical companies. He is a Lead Investigator for the Embolden Study (Astra-Zeneca), the BCI Neuroplasticity Study and the Aripiprazole Mania Study, and is involved in investigator-initiated studies from Astra-Zeneca, Eli Lilly, Lundbeck, and Wyeth. In addition, he has received grant funding (past and present) from the National Institute of Mental Health (NIMH, USA), Canadian Institutes of Health Research (CIHR, Canada), National Alliance for Research on Schizophrenia and Depression (NARSAD, USA), Stanley Medical Research Institute (USA), Medical Research Council (MRC, UK), Wellcome Trust (UK), Royal College of Physicians (Edinburgh), British Medical Association (BMA, UK), UBC-VGH Foundation (Canada), Western Economic Diversification Canada (WEDC, Canada), CCS Depression Research Fund (Canada), Michael Smith Foundation for Health Research (MSFHR, Canada), and the National Institute for Health Research (NIHR, UK).
Giuseppe Maina received grant funding, consulting fees and reimbursements from Lundbeck Italia, Otsuka, Pfizer Italia, Janssen Cilag, and Astra Zeneca.
Anna Coluccia, Alessandro Cuomo, Arianna Goracci, and Rocco N. Forgione declare they have no conflicts of interest.
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Fagiolini, A., Coluccia, A., Maina, G. et al. Diagnosis, Epidemiology and Management of Mixed States in Bipolar Disorder. CNS Drugs 29, 725–740 (2015). https://doi.org/10.1007/s40263-015-0275-6
- Bipolar Disorder
- Mixed State