Review
New treatment guidelines for acute bipolar depression: A systematic review

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Summary

Introduction

Bipolar depression poses a great burden on patients and their families due to its duration, associated functional impairment, and limited treatment options. Given the complexity of the disorder and the advances in treatment, a number of clinical guidelines, consensus statements and expert opinions were developed with the aim to standardize treatment and provide clinicians with treatment algorithms for every-day clinical practice. Unfortunately, they often led to conflicting conclusions and recommendations due to limitations of the available literature. As findings emerge from research literature, guidelines quickly become obsolete and need to be updated or revised. Many guidelines have been updated in the last 5 years, after the last review of bipolar disorder (BD) treatment guidelines.

Objective

The purpose of this work is to systematically review guidelines, consensus meetings and treatment algorithms on the acute treatment of bipolar depression updated or published since 2005, to critically underline common and critical points, highlight limits and strengths, and provide a starting point for future research

Materials and methods

The MEDLINe/PubMed/Index Medicus, PsycINFO/PsycLIT, Excerpta Medica/EMBASE, databases were searched using “depression”, “bipolar”, “manic-depression”, “manic-depressive” and “treatment guidelines” as key words

Results

The search returned 204 articles. Amongst them, there were 28 papers concerning structured treatment algorithms and/or guidelines suggested by official panels. After excluding those guidelines that were not performed by scientific societies or international groups and those published before 2005, the final selection yielded 7 papers When looking into guidelines content, the results indicate a trend to the gradual acceptance of the use of the atypical antipsychotic quetiapine as monotherapy as first-line treatment. Antidepressant monotherapy is discouraged in most of them, although some support the use of antidepressants in combination with antimanic agents for a limited period of time. Lamotrigine has become a highly controversial option.

Conclusion

The management of bipolar depression is complex and should be differentiated from management of unipolar depression. Guidelines may be useful instruments for helping clinicians to choose and plan bipolar depression treatment by integrating the more updated scientific knowledge with every-day clinical practice and patient-specific factors; however, a further effort is needed in order to improve guidelines implementation in clinical practice. The latest updates on treatment guidelines for bipolar depression give priority to novel treatment approaches, such as quetiapine, over more traditional ones, such as lithium or antidepressants. Lamotrigine is a controversial option.

Introduction

Bipolar disorder (BD) is a chronic, disabling and heterogeneous condition of major relevance, whose treatment needs to be considered separately through the course of the illness for manic/hypomanic, mixed and depressive episodes (Fountoulakis et al., 2008). Given the complexity of the disorder and the advances in therapeutic options, the need to standardize the treatment of bipolar disorder has emerged allowing the publication of a number of treatment guidelines. A guideline is an advice, a non-mandatory algorithm of practice, to achieve a defined outcome. A clinical guideline represents a synthesis of the best available scientific knowledge regarding a specific topic. It is supposed to help clinicians to choose a proper treatment for a specific condition. It is usually developed by multidisciplinary teams (health professionals, patients and methodologists) through standardized and systematic methods, which integrate evidence-based data (mostly, but not only, from randomized clinical trials-RCTs) with the rational clinical practice and experience. Usually, available data are evaluated and ranked on the basis of the methodology of the study design, the number of positive trials and the absence or presence of negative evidence. Finally, each compound is assigned a Level or Category of evidence (CE), which basically describes the level of efficacy. Subsequently, different Clinical recommendations or Recommendation Grades (RG) are additionally assigned, which integrate additional clinical aspects of safety, tolerability and effectiveness.

Depression is the phase of bipolar illness which probably represents the greatest burden on patients. Bipolar patients spent three times more days fulfilling criteria for depression than for any other mood episode and the continuous presence of subthreshold depressive symptomatology may be the rule rather than the exception (Judd et al., 2008, Kupka et al., 2007, Judd et al., 2008). Treatment options for bipolar depression are provided by almost all available treatment guidelines, despite data in this field is relatively scanty if we consider that most studies focus on the treatment of mania or hypomania rather than depression. Fountoulakis and colleagues reviewed in 2005 twenty-seven guidelines on treatment of BD and concluded that recommendations for bipolar depression were poorly represented across guidelines. Basically, almost every guideline suggested the use of antidepressant agents only in combination with an antimanic agent, in order to avoid manic switches. Stress on the effectiveness of lamotrigine in bipolar depression was another common element to almost all available guidelines. Since 2005, many guidelines have been updated or revised, including those of the World Federation of Societies of Biological Psychiatry (WFSBP) (Grunze et al., 2010; Grunze et al., 2009), of the Canadian Network for Mood and Anxiety Treatments (CANMAT), of the International Society for Bipolar Disorders (ISBD) (Yatham et al., 2009), of the British Association for Psychopharmacology (BAP) (Goodwin, 2009), and of the National Institute for Health and Clinical Excellence (NICE, 2009). Considering the growing interest for bipolar depression, new guidelines and updates were specifically developed, namely, the ECNP Consensus Meeting on Bipolar depression (Goodwin et al., 2008) and the International Consensus Group on the Evidence-Based Pharmacologic Treatment of Bipolar I and II Depression (Kasper et al., 2008).

The application of well-designed guidelines may be potentially helpful to clinicians and carry substantial benefits to bipolar depressed patients (Dennehy et al., 2005, Perlis, 2007). However, some weaknesses should also be highlighted; the several existing guidelines offer huge variability on their recommendations, they quickly become obsolete and need regular updating, they are often difficult to translate to every-day practice (Vieta et al., 2007) and, especially when it comes to bipolar depression, treatment options are quite scanty. Given the important number of guidelines updated since 2005, and the need for clinicians to apply guidelines in a more effective, patient-friendly and truly practical way (Vieta, 2009), the purpose of this work is to systematically review guidelines, consensus meeting and treatment algorithms which concern bipolar depression, published or updated since 2005. The final aim of our work is to critically review recently updated guidelines focusing exclusively on the treatment of bipolar depression in order to stress existing areas of consensus or controversy, highlight limits and strengths, and provide starting points for future research.

Section snippets

Methods

An extensive search for relevant national and international treatment guidelines, consensus statements and comprehensive reviews published since 2005 was undertaken. The data used for this review have been extracted from the following electronic databases: MEDLINe/PubMed/Index Medicus, PsycINFO/PsycLIT, Excerpta Medica/EMBASE, the Science Citation Index at Web of Science (ISI), and the Cochrane library. The literature search was performed using the MeSH heading “bipolar disorder” and using

Results of the literature search

The search returned 204 articles. Amongst them, there were 28 papers concerning structured treatment algorithms and/or guidelines suggested by official panels. This final selection yielded 7 papers. Another unpublished guideline was the American Psychiatric Association guideline. Unfortunately, it could not be included in this review due to current legislation restrictions. All major guideline sources and treatment algorithms updated after 2005 are summarized Table 1.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2009 on the treatment of acute bipolar depression (Grunze et al., 2010)

The task force of the World

Discussion

Bipolar depression is a complex condition which poses several diagnostic and therapeutic challenges. Since it is different from unipolar depression both in terms of pathoplasty, outcome and management, treatment options should be differentiated accordingly. However, many options in clinical practice may be wrongly translated from unipolar to bipolar depression in clinical practice. For instance, since all ADs are officially approved for the treatment of major depression without distinguishing

Conclusion

Although guidelines cannot substitute professional knowledge and clinical judgement, they might be a useful tool for clinicians in order to orientate their practice towards evidence base. The management of depression in patients with bipolar disorder is complex and should be differentiated from the management of unipolar depression.

Treatment guidelines for bipolar depression are not easy to compare, reflecting how limited the evidence-base is, but one trend that is increasingly becoming obvious

Role of funding source

This work was partly supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, CIBERSAM and the support of the Generalitat de Catalunya to the Bipolar Disorders Group (2009 SGR 1022).

Conflicts of interests

Dr. Vieta has received grants and served as consultant, advisor or speaker for the following entities: Almirall, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest Research Institute, Glaxo-Smith-Kline, Janssen-Cilag, Jazz, Johnson & Johnson, Lundbeck, Merck, Novartis, Organon, Otsuka, Pfizer, Sanofi-Aventis, Servier, Shering-Plough, Takeda, the Spanish Ministry of Science and Innovation (CIBERSAM), the Seventh European Framework Programme (ENBREC), the Stanley Medical Research Institute,

Acknowledgments

This work was supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, CIBERSAM and the support of the Generalitat de Catalunya to the Bipolar Disorders Group (2009 SGR 1022).

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