Unmet Needs in Psychiatry: Bipolar Depression

  • Ross J. BaldessariniEmail author
  • Leonardo Tondo
  • Gustavo H. Vázquez


Depressive phases of bipolar disorders (BD) present major challenges for treatment and comprehensive clinical management. They are the main component of psychiatric morbidity in BD, even with treatment, and are associated with excess morbidity and mortality from co-occurring general-medical disorders as well as very high suicide risk. BD patients exceed the general population in risks for a range of medical disorders, notably including metabolic syndrome marked by obesity and diabetes, as well as cardiovascular disorders including congestive heart failure and stroke. Some of these may have a selective relationship with bipolar depression as well as reflecting overall psychiatric morbidity. Resulting mortality rates are several-times higher than in the general population and some other psychiatric disorders. Suicide risk is approximately 20-times above general-population rates, greater than with most other major psychiatric disorders, and strongly associated with mixed (agitated-dysphoric) and depressive phases of BD. Specific, clinically effective prediction of individual suicidal behavior and its timing is very limited. Treatments that may reduce suicide risk, including lithium and perhaps clozapine or ketamine, are not securely proved effective or remain untested. Treatment of bipolar depression is far less well investigated than unipolar depression, and the value of antidepressants effective in short-term and prophylactic treatment of major depressive disorder remains controversial for bipolar depression and they are best avoided with current agitated-mixed dysphoric states. For bipolar depression, evidence of efficacy of mood-stabilizing agents, including lithium and several anticonvulsants (except lamotrigine, long-term) remains limited; emerging use of modern antipsychotics is encouraging for short-term treatment of acute bipolar depression, especially with mixed features. All available treatments used for bipolar depression present risks that include adverse metabolic and neurological effects.


Bipolar disorder Depression Disability Morbidity Mortality Suicide 



Supported by a grant from the Bruce J Anderson Foundation and by the McLean Private Donors Psychiatry Research Fund (to RJB), and a grant from the Aretaeus Foundation of Rome (to LT).


No author or immediate family member has financial relationships with commercial organizations that might appear to represent potential conflicts of interest with the material presented.


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Ross J. Baldessarini
    • 1
    • 2
    Email author
  • Leonardo Tondo
    • 1
    • 2
    • 3
  • Gustavo H. Vázquez
    • 2
    • 4
  1. 1.Department of PsychiatryHarvard Medical SchoolBostonUSA
  2. 2.International Consortium for Bipolar & Psychotic Disorders Research, McLean HospitalBelmontUSA
  3. 3.Lucio Bini Mood Disorder CenterCagliariItaly
  4. 4.Department of PsychiatryQueen’s University School of MedicineKingstonCanada

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