CNS Spectrums

Review Articles

Treatment of bipolar depression

Laura Musettia1 c1, Claudia Del Grandea1, Donatella Marazzitia1 and Liliana Dell'Ossoa1

a1 Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy


Depressive symptoms and episodes dominate the long-term course of bipolar disorder and are associated with high levels of disability and an increased risk of suicide. However, the treatment of bipolar depression has been poorly investigated in comparison with that of manic episodes and unipolar major depressive disorder. The goal of treatment in bipolar depression is not only to achieve full remission of acute symptoms, but also to avoid long-term mood destabilization and to prevent relapses. A depressive presentation of bipolar disorder may often delay the appropriate management and, thus, worsen the long-term outcome. In these cases, an accurate screening for diagnostic indicators of a possible bipolar course of the illness should guide the therapeutic choices, and lead to prognostic improvement. Antidepressant use is still the most controversial issue in the treatment of bipolar depression. Despite inconclusive evidence of efficacy and tolerability, this class of agents is commonly prescribed in acute and long-term treatment, often in combination with mood stabilizers. In this article, we review available treatment options for bipolar depression, and we shall provide some suggestions for the management of the different presentations of depression in the course of bipolar disorder.

(Received October 31 2012)

(Accepted December 11 2012)

(Online publication February 08 2013)

Key words

  • Antidepressants;
  • atypical antipsychotics;
  • bipolar depression;
  • bipolar spectrum;
  • depressive mixed state;
  • mood stabilizers;
  • nonpharmacological treatment;
  • pharmacological treatment


c1 Address for correspondence: Laura Musetti, MD, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56100 Pisa, Italy. (Email