CNS Drugs

, Volume 27, Issue 7, pp 515–529 | Cite as

Pharmacological Management of Bipolar Depression: Acute Treatment, Maintenance, and Prophylaxis

Therapy in Practice


Although the most distinctive clinical feature of bipolar disorder is the pathologically elevated mood, it does not usually constitute the prevalent mood state of bipolar illness. The majority of patients with bipolar disorder spend much more time in depressive episodes, including subsyndromal depressive symptoms, and bipolar depression accounts for the largest part of the morbidity and mortality of the illness. The pharmacological treatment of bipolar depression mostly consists of combinations of at least two drugs, including mood stabilizers (lithium and anticonvulsants), atypical antipsychotics, and antidepressants. Antidepressants are the most frequently prescribed drugs, but recommendations from evidence-based guidelines are not conclusive and do not overtly support their use. Among antidepressants, best evidence exists for fluoxetine, but in combination with olanzapine. Although some guidelines recommend the use of selective serotonin reuptake inhibitors or bupropion in combination with antimanic agents as first-choice treatment, others do not, based on the available evidence. Among anticonvulsants, the use of lamotrigine is overall recommended as a first-line choice, but acute monotherapy studies have failed. Valproate is generally mentioned as a second-line treatment. Lithium monotherapy is also suggested by most guidelines as a first-line treatment, but its efficacy in acute use is not totally clear. Amongst atypical antipsychotics, quetiapine, in monotherapy or as adjunctive treatment, is recommended by most guidelines as a first-line choice. Olanzapine monotherapy is also suggested by some guidelines and is approved in Japan. Armodafinil, pramipexole, ketamine, and lurasidone are recent proposals. Long-term treatment in bipolar disorder is strongly recommended, but guidelines do not recommend the use of antidepressants as a maintenance treatment. Lithium, lamotrigine, valproate, olanzapine, quetiapine, and aripiprazole are the recommended first-line maintenance options.



Professor Vieta and Dr. Valentí declare no sources of funding were used to prepare this review.

Professor Vieta has received research grants and served as consultant, advisor, or speaker for Alexza, Almirall, AstraZeneca, Bial, Bristol-Myers Squibb, Elan, Eli Lilly, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo-Smith-Kline, Janssen-Cilag, Jazz, Johnson & Johnson, Lundbeck, Merck-Sharp and Dohme, Novartis, Organon, Otsuka, Pfizer, Pierre Fabre, Qualigen, Roche, Sanofi-Aventis, Servier, Sherling-Plough, Shire, Solvay, Takeda, Teva, United Biosource Corporation, and Wyeth; and has received research funding from the Catalan, Spanish, and European Governments. Dr. Valentí has served as a speaker for Abbott, and Bristol-Myers Squibb.


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© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.Bipolar Disorders Program, Hospital ClinicUniversity of Barcelona, IDIBAPS, CIBERSAMBarcelonaSpain

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