ReviewNew treatment guidelines for acute bipolar depression: A systematic review
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).
References (77)
- et al.
Venlafaxine monotherapy in women with bipolar II and unipolar major depression
J. Affect. Disord.
(2000) - et al.
Divalproex in the treatment of bipolar depression: a placebo-controlled study
J. Affect. Disord.
(2005) - et al.
Treatment guidelines for bipolar disorder: a critical review
J. Affect. Disord.
(2005) - et al.
Treatment of bipolar depression: an update
J. Affect. Disord.
(2008) - et al.
In-patient care costs of patients with bipolar I disorder: a comparison between two European centers
J. Affect. Disord.
(2010) - et al.
ECNP consensus meeting. Bipolar depression. Nice, March 2007
Eur. Neuropsychopharmacol.
(2008) - et al.
Adjunctive quetiapine in bipolar patients partially responsive to lithium or valproate
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2003) - et al.
The effectiveness of carbamazepine in unipolar depression: a double-blind, randomized, placebo-controlled study
J. Affect. Disord.
(2008) - et al.
Toward a clinical delineation of dysphoric hypomania — operational and conceptual dilemmas
Bipolar Disord.
(2005) Efficacy and safety of venlafaxine in the treatment of bipolar II major depressive episode
J. Clin. Psychopharmacol.
(1998)
Does lithium treatment still work? Evidence of stable responses over three decades
Arch. Gen. Psychiatry
The clinical use of carbamazepine in affective disorder
J. Clin. Psychiat.
Generalizability of clinical trial results for major depression to community samples: results from the National Epidemiologic Survey on Alcohol and Related Conditions
J. Clin. Psychiatry
A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder
Arch. Gen. Psychiatry
A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression
J. Clin. Psychiatry
Olanzapine/fluoxetine combination vs. lamotrigine in the 6-month treatment of bipolar I depression
Int. J. Neuropsychopharmacol.
A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder
J. Clin. Psychiatry
Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder
Am. J. Psychiatry
Long-term treatment of bipolar disorder with lamotrigine
J. Clin. Psychiatry
International consensus group on bipolar I depression treatment guidelines
J. Clin. Psychiatry
A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression
Am. J. Psychiatry
Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials
Bipolar Disord.
The road to DSM-V. Bipolar Disorder Episode and Course Specifiers
Psychopathology
Does provider adherence to a treatment guideline change clinical outcomes for patients with bipolar disorder? Results from the Texas Medication Algorithm Project
Psychol. Med.
Validation of the American Thoracic Society-Infectious Diseases Society of America Guidelines for Hospital-Acquired Pneumonia in the Intensive Care Unit
Clin. Infect. Dis
Treatment of bipolar disorder: a systematic review of available data and clinical perspectives
Int. J. Neuropsychopharmacol.
A placebo controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders
J. Clin. Psychopharmacol.
New trial should clarify lithium use in bipolar disorder
BMJ
Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials
Br. J. Psychiatry
Antidepressants in bipolar disorder: the case for caution
Bipolar Disord.
Divalproex in the treatment of acute bipolar depression: a preliminary double-blind, randomized, placebo-controlled pilot study
J. Clin. Psychiatry
ISBD, Diagnostic Guidelines Task Force. Diagnostic guidelines for bipolar disorder: a summary of the International Society for Bipolar Disorders Diagnostic Guidelines Task Force Report
Bipolar Disord.
Long-term antidepressant treatment in bipolar disorder: meta-analyses of benefits and risks
Acta Psychiatr. Scand.
Antidepressants for bipolar depression: a systematic review of randomized, controlled trials
Am. J. Psychiatry
Adjunctive antidepressant use and symptomatic recovery among bipolar depressed patients with concomitant manic symptoms: findings from the STEP-BD
Am. J. Psychiatry
Consensus Group of the British Association for Psychopharmacology. Evidence-based guidelines for treating bipolar disorder: recommendations from the British Association for Psychopharmacology
J. Psychopharmacol.
Evidence-based guidelines for treating bipolar disorder: revised second edition—recommendations from the British Association for Psychopharmacology Journal of Psychopharmacology
J. Psychopharmacol.
Manic-depressive illness
Cited by (122)
Bipolar and related disorders
2023, Encyclopedia of Mental Health, Third Edition: Volume 1-3Early electroconvulsive therapy in patients with bipolar depression: A propensity score-matched analysis using a nationwide inpatient database
2022, Journal of Affective DisordersCitation Excerpt :Only one randomized controlled trial (RCT) of ECT for bipolar depression with a small sample size has been conducted to date due to the difficulties of randomization and double-blind evaluation, as well as the exclusion of patients at high suicide risk and those who cannot consent to participate from the study (Schoeyen et al., 2015). Therefore, recommendation levels of ECT for bipolar depression in the guidelines are low (Fountoulakis et al., 2017; Goodwin and Consensus Group of the British Association for Psychopharmacology, 2009; Malhi et al., 2015; Nivoli et al., 2011; Yatham et al., 2018), and the effect of early ECT for bipolar depression remains unclear. Therefore, this study aimed to clarify how early ECT for bipolar depression affects the length of hospital stay by using a large national inpatient database in Japan.
Complete evaluation of retinal function in Major Depressive Disorder: From central slowdown to hyperactive periphery
2021, Journal of Affective DisordersPredictors of conversion from major depressive disorder to bipolar disorder
2021, Psychiatry Research