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Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on pharmacopsychiatry

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Abstract

The current statement is a systematic review of the available data concerning the efficacy of medication treatment of bipolar disorder (BP). A systematic MEDLINE search was made concerning the treatment of BP (RCTs) with the names of treatment options as keywords. The search was updated on 10 March 2012. The literature suggests that lithium, first and second generation antipsychotics and valproate and carbamazepine are efficacious in the treatment of acute mania. Quetiapine and the olanzapine–fluoxetine combination are also efficacious for treating bipolar depression. Antidepressants should only be used in combination with an antimanic agent, because they can induce switching to mania/hypomania/mixed states/rapid cycling when utilized as monotherapy. Lithium, olanzapine, quetiapine and aripiprazole are efficacious during the maintenance phase. Lamotrigine is efficacious in the prevention of depression, and it remains to be clarified whether it is also efficacious for mania. There is some evidence on the efficacy of psychosocial interventions as an adjunctive treatment to medication. Electroconvulsive therapy is an option for refractory patients. In acute manic patients who are partial responders to lithium/valproate/carbamazepine, adding an antipsychotic is a reasonable choice. The combination with best data in acute bipolar depression is lithium plus lamotrigine. Patients stabilized on combination treatment might do worse if shifted to monotherapy during maintenance, and patients could benefit with add-on treatment with olanzapine, valproate, an antidepressant, or lamotrigine, depending on the index acute phase. A variety of treatment options for BP are available today, but still unmet needs are huge. Combination therapy may improve the treatment outcome but it also carries more side-effect burden. Further research is necessary as well as the development of better guidelines and algorithms for the step-by-step rational treatment.

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Conflict of interest

Dr Fountoulakis is/was a member of the International Consultation Board of Wyeth for desvenlafaxine, BMS for aripiprazole in BP and Servier for agomelatine and has received honoraria for lectures from AstraZeneca, Janssen-Cilag, Eli Lilly and research grants from AstraZeneca and Pfizer Foundation.

Dr Tandon has no conflict of interest.

Dr Okasha has received honoraria as a speaker for Lundbeck, Eli Lilly, Pfizer, Janssen-Cilag, Novartis, GlaxoSmithKline, Astra Zeneca, Otsuka and Servier.

Dr Moeller has received grants or is a consultant for and on the speakership bureaus of AstraZeneca, Bristol-Myers Squibb, Eisai, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Merck, Novartis, Organon, Pfizer, Sanofi-Aventis, Schering-Plough, Schwabe, Sepracor, Servier and Wyeth.

Dr Severus is on the speaker’s bureau of Lundbeck, AstraZeneca and Eli Lilly.

Dr Andreassen has received speaker’s honorarium from Lundbeck, AstraZeneca, Janssen, BMS and Eli Lilly, and unrestricted educational grant from Eli Lilly, as well as research stipend/awards from Lundbeck and Eli Lilly.

Dr Kasper has received grants/research support from Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Organon, Pfizer, Sepracor, Servier. He is or has served as consultant/advisory board for AstraZeneca, Austrian National Bank (OENB), Bristol-Myers Squibb, Eli Lilly, German Research Foundation (DFG), GlaxoSmithKline, Janssen, Lundbeck, Merck Sharp and Dome (MSD), Organon, Pfizer, Schwabe, Sepracor, Servier, Supervisory Boards of Universities. He is or was with the speaker’s bureau for Angelini, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Lundbeck, Merck Sharp and Dome (MSD), Organon, Pierre Fabre, Pfizer, Schwabe, Sepracor, Servier.

Dr Blier has received research support and/or honoraria for speaking engagements or participation in advisory boards from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Euthymics, Johnson and Johnson, Lundbeck, Merck, Pierre Farbre, Pfizer, Servier and Takeda.

Dr Vieta has received grants and served as consultant, advisor or CME speaker for the following entities: Almirall, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Research Institute, Gedeon Richter, GlaxoSmithKline, Janssen-Cilag, Jazz, Johnson & Johnson, Lundbeck, Merck, Novartis, Organon, Otsuka, Pfizer, Pierre Fabre, Qualigen, Sanofi-Aventis, Servier, Shering-Plough, Solvay, Takeda, the Spanish Ministry of Science and Innovation (CIBERSAM), the Seventh European Framework Programme (ENBREC), the Stanley Medical Research Institute, United Biosource Corporation and Wyeth.

This supplement was not sponsored by outside commercial interests. It was funded entirely by the authors.

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Correspondence to Konstantinos N. Fountoulakis.

Appendix: Members of the WPA section on pharmacopsychiatry

Appendix: Members of the WPA section on pharmacopsychiatry

Dag Aarsland, Carlo Altamura, Ole A. Andreassen, Thomas Baghai, David S. Baldwin, David Baron, Michael Bauer, Pierre Blier, William E. Bunney, Graham Burrows, Nuria Cruz, Mahmoud M. Elhabiby, Wolfgang Fleischhacker, Daniel Flores, Orestes V. Forlenza, Kostas N. Fountoulakis, Raphael Gaillard, W.F. Gattaz, Catherine Harmer, Gerardo Heinze, Ian Hindmarch, Cyril Hoschl, Siegfried Kasper, Chan-Hyung Kim, Alexandra E. Kutzelnigg, Brian Leonard, Yechiel Levkovitz, Juan J. Lopez-Ibor, Massimo Carlo Mauri, Bruno Millet, Hans-Jürgen Möller, Warrier Mohandas, Francisco Roma Nava, Ahmed Okasha, Jean Pierre Olie, Eugene S. Paykel, Giorgio Racagni, Maria Rettenbacher, Raben Rosenberg, Bernd Saletu, Bruce Singh, Dan J. Stein, Rajiv Tandon, Marcio Versiani, Eduard Vieta, Nic J.A. van der Wee, Gregers Wegener, Joseph Wu, Jon Sang Yoon, Joseph Zohar.

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Fountoulakis, K.N., Kasper, S., Andreassen, O. et al. Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on pharmacopsychiatry. Eur Arch Psychiatry Clin Neurosci 262 (Suppl 1), 1–48 (2012). https://doi.org/10.1007/s00406-012-0323-x

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