The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Update 2009 on the Treatment of Acute Mania

Abstract

These updated guidelines are based on a first edition that was published in 2003, and have been edited and updated with the available scientific evidence until end of 2008. Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of acute mania in adults. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, from the clinical trial database clinicaltrials.gov, from recent proceedings of key conferences, and from various national and international treatment guidelines. Their scientific rigor was categorised into six levels of evidence (A–F). As these guidelines are intended for clinical use, the scientific evidence was finally asigned different grades of recommendation to ensure practicability.

• Bipolar disorder
• mania
• depression
• acute treatment
• evidence-based guidelines
• pharmacotherapy
• antipsychotics
• mood stabiliser
• electroconvulsive therapy

Notes

¹A: Full evidence from controlled studies is based on: two or more double-blind, parallel-group, randomized controlled studies (RCTs) showing superiority to placebo (or in the case of psychotherapy studies, superiority to a “psychological placebo” in a study with adequate blinding) and one or more positive RCT showing superiority to or equivalent efficacy compared with established comparator treatment in a three-arm study with placebo control or in a well-powered non-inferiority trial (only required if such a standard treatment exists). In the case of existing negative studies (studies showing non-superiority to placebo or inferiority to comparator treatment), these must be outweighed by at least two more positive studies or a meta-analysis of all available studies showing superiority to placebo and non-inferiority to an established comparator treatment. Studies must fulfill established methodological standards.The decision is based on the primary efficacy measure.

²Recommendation Grade 2 corresponds to “ Category A evidence and moderate risk-benefit ratio”.

³B: Limited positive evidence from controlled studies is based on: one or more RCTs showing superiority to placebo (or in the case of psychotherapy studies, superiority to a “psychological placebo”) or a randomized controlled comparison with a standard treatment without placebo control with a sample size sufficient for a non-inferiority trial or one or more sufficiently powered post-hoc analyses of RCTs showing superiority to placebo (or in the case of psychotherapy studies, superiority to a “psychological placebo”). In the case of existing negative studies (studies showing non-superiority to placebo or inferiority to comparator treatment), these must be outweighed by at least one more positive study or a meta-analysis of all available studies showing superiority to placebo or non-inferiority to an established comparator treatment.

⁴C1 evidence is based on: one or more positive naturalistic open studies (with a minimum of five evaluable patients) or a comparison with a reference drug with a sample size insufficient for a non-inferiority trial and no negative controlled studies exist).

⁵E: The majority of RCTs studies or exploratory studies shows non-superiority to placebo (or in the case of psychotherapy studies, superiority to a “psychological placebo”) or inferiority to comparator treatment

⁶F: Adequate studies proving efficacy or non-efficacy are lacking. If existing, open studies or case reports showed a total lack of efficacy

⁷If long-term treatment is considered at the same time, the RG for lithium is “1”.

⁸A fixed dose of 20 mg olanzapine was sufficient to demonstrate significant antimanic effects in females with moderate to severe mania (Bech et al. 2006). However, females achieve significantly higher plasma concentrations of olanzapine than males (Kelly et al. 1999, 2006). This may imply that higer doses are needed in males with moderate to severe mania (Goodwin and Jamison 2007).

⁹Valproate is not recommended as first choice treatment (RG “1”) in women of child-bearing age.

¹⁰The RG for ziprasidone is “2” in countries where its use is restricted due to regulatory order.