Guidelines For Treatment Of Bipolar Disorder Research Articles

Global perspectives on bipolar disorder treatment: in-depth comparative analysis of international guidelines for medication selection.

Bipolar disorder, a chronic mental health condition characterised by fluctuations in mood, energy and functionality, affects millions of individuals worldwide. Its management requires a comprehensive approach, and, as such, treatment guidelines have a pivotal role in guiding clinicians to alleviate symptoms, prevent relapse and enhance overall patient well-being. However, the treatment landscape is far from homogenous, with significant variations existing across different countries. This study aimed to explore and compare treatment guidelines for bipolar disorder in various regions, shedding light on the factors that influence therapeutic approaches and thus offering insights that could contribute to the ongoing refinement of evidence-based practices in management. The study explores various international treatment guidelines for bipolar disorder that have been updated after 2014. Guidelines from the UK, Canada, Australia/New Zealand, South Korea and the International College of Neuropsychopharmacology are scrutinised to identify factors contributing to the observed differences among them. The variations in recommended drugs across guidelines arise from the approaches employed in guideline development - whether relying on expert consensus or meta-analysis results. Timing disparities in conducting these analyses and the selection of studies also exert influence. Moreover, differences in metabolic enzymes among diverse races and the health policies implemented by individual nations play a significant part in shaping these differences. The primary hindrance to consistent treatment conclusions lies in the scarcity of high-quality research results, leading to variations in guidelines. Enhancing evidence-based recommendations necessitates the undertaking of large-scale studies dedicated to assessing treatments for bipolar disorder.

Comparative Review of Pharmacological Treatment Guidelines for Bipolar Disorder

Comparative Review of Pharmacological Treatment Guidelines for Bipolar Disorder

Special Report: Bipolar Disorder II—Frequently Neglected, Misdiagnosed

Special Report: Bipolar Disorder II—Frequently Neglected, Misdiagnosed

Lithium stabilization and misunderstandings: Toward understanding why lithium is underutilized.

In a recent Editorial, Malhi et al.1 stress how underutilized lithium is and the importance of rectifying this deficiency. Across published treatment guidelines for bipolar disorder, lithium is universally considered the gold standard and the recommended first line treatment for prophylaxis. So, why is it then prescribed less and less? In addition to the crucial points raised by Malhi et al.1 , we offer an explanation from decades of clinical and neuroscience research involving bipolar patients and their family members.

Exploring the clinical outcome of Mindfulness-Based Cognitive Therapy for bipolar and unipolar depressive patients in routine clinical practice: a pilot study

BackgroundMindfulness Based Cognitive Therapy (MBCT) has been adopted as an evidence-based treatment for unipolar depressive disorder (UDD). Although MBCT has not been included in the treatment guidelines for bipolar disorder (BD), MBCT is regularly being offered to patients with BD in routine clinical practice. In this pilot study we used routine outcome monitoring (ROM) data to explore whether there are indications that patients with BD might benefit less from MBCT than patients with UDD in terms of feasibility and effectiveness.MethodsThe study population consisted of patients with BD (n = 30) or UDD (n = 501) who received MBCT at the Radboudumc Centre for Mindfulness in Nijmegen, the Netherlands. Patients completed self-report measures of depressive symptom severity, worry, well-being, mindfulness skills and self-compassion pre- and post MBCT as part of the ROM.ResultsThere were significant less patients with BD who decided to start MBCT after intake than patients with UDD. No differences in dropout between groups were found. Results showed significant moderate to large improvements in both groups after MBCT, while no differences between groups were found, on all outcome measures.ConclusionsThis study demonstrates that there are no indications that MBCT, when delivered in heterogeneous patient groups in routine clinical practice, is less beneficial for patients with BD than patients with UDD in terms of feasibility and effectiveness. This lends support to conduct an adequately powered RCT to examine the (cost-)effectiveness of MBCT in BD as the next step before implementing MBCT on a larger scale in patients with BD.

A nationwide study on concordance with multimodal treatment guidelines in bipolar disorder

BackgroundMost previous studies on concordance with treatment guidelines for bipolar disorder focused on pharmacotherapy. Few studies have included other treatment modalities.AimsTo study concordance with the Dutch guideline of various treatment modalities in outpatient treatment settings for patients with bipolar disorder and to identity factors associated with concordance.MethodsA nationwide non-interventional study using psychiatrists’ and patients’ surveys.Results839 patients with bipolar or schizoaffective disorder bipolar type were included. Concordance with the guideline was highest for participation of a psychiatrist in the treatment (98%) and for maintenance pharmacotherapy (96%), but lower for supportive treatment (73.5%), use of an emergency plan (70.6%), psychotherapy (52.2%), group psychoeducation (47.2%), and mood monitoring (47%). Presence of a written treatment plan, a more specialized treatment setting, more years of education, and diagnosis of bipolar I disorder versus bipolar II, bipolar NOS, or schizoaffective disorder were significantly associated with better concordance.ConclusionIn contrast to pharmacotherapy, psychosocial treatments are only implemented to a limited extend in everyday clinical practice in bipolar disorder. More effort is needed to implement non-pharmacological guideline recommendations for bipolar disorder.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third‐ line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment‐emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second‐ line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence‐based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first‐line treatments for acute mania. First‐line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first‐line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm

Background:The current paper includes a systematic search of the literature, a detailed presentation of the results, and a grading of treatment options in terms of efficacy and tolerability/safety.Material and Methods:The PRISMA method was used in the literature search with the combination of the words ‘bipolar,’ ‘manic,’ ‘mania,’ ‘manic depression,’ and ‘manic depressive’ with ‘randomized,’ and ‘algorithms’ with ‘mania,’ ‘manic,’ ‘bipolar,’ ‘manic-depressive,’ or ‘manic depression.’ Relevant web pages and review articles were also reviewed.Results:The current report is based on the analysis of 57 guideline papers and 531 published papers related to RCTs, reviews, posthoc, or meta-analysis papers to March 25, 2016. The specific treatment options for acute mania, mixed episodes, acute bipolar depression, maintenance phase, psychotic and mixed features, anxiety, and rapid cycling were evaluated with regards to efficacy. Existing treatment guidelines were also reviewed. Finally, Tables reflecting efficacy and recommendation levels were created that led to the development of a precise algorithm that still has to prove its feasibility in everyday clinical practice.Conclusions:A systematic literature search was conducted on the pharmacological treatment of bipolar disorder to identify all relevant random controlled trials pertaining to all aspects of bipolar disorder and graded the data according to a predetermined method to develop a precise treatment algorithm for management of various phases of bipolar disorder. It is important to note that the some of the recommendations in the treatment algorithm were based on the secondary outcome data from posthoc analyses.

The International College of Neuropsychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 1: Background and Methods of the Development of Guidelines.

Background:This paper includes a short description of the important clinical aspects of Bipolar Disorder with emphasis on issues that are important for the therapeutic considerations, including mixed and psychotic features, predominant polarity, and rapid cycling as well as comorbidity.Methods:The workgroup performed a review and critical analysis of the literature concerning grading methods and methods for the development of guidelines.Results:The workgroup arrived at a consensus to base the development of the guideline on randomized controlled trials and related meta-analyses alone in order to follow a strict evidence-based approach. A critical analysis of the existing methods for the grading of treatment options was followed by the development of a new grading method to arrive at efficacy and recommendation levels after the analysis of 32 distinct scenarios of available data for a given treatment option.Conclusion:The current paper reports details on the design, method, and process for the development of CINP guidelines for the treatment of Bipolar Disorder. The rationale and the method with which all data and opinions are combined in order to produce an evidence-based operationalized but also user-friendly guideline and a specific algorithm are described in detail in this paper.

The International College of Neuropsychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 4: Unmet Needs in the Treatment of Bipolar Disorder and Recommendations for Future Research.

Background:The current fourth paper on the International College of Neuropsychopharmacology guidelines for the treatment of bipolar disorder reports on the unmet needs that became apparent after an extensive review of the literature and also serves as a conclusion to the project of the International College of Neuropsychopharmacology workgroup.Materials and Methods:The systematic review of the literature that was performed to develop the International College of Neuropsychopharmacology guidelines for bipolar disorder identified and classified a number of potential shortcomings.Results:Problems identified concerned the reliability and validity of the diagnosis of bipolar disorder and especially of bipolar depression. This, in turn, has profound consequences for early detection and correct treatment of the disorder. Another area that needs improvement is the unsatisfactory efficacy and effectiveness of therapeutic options, especially in special populations such as those with mixed features and rapid cycling course. Gender issues and adherence problems constitute an additional challenge. The literature suggests that while treatment providers are concerned more with treatment-related issues, patients and their caregivers worry more about issues pertaining to the availability of services and care, quality of life, and various types of burden. The workgroup identified additional unmet needs related to the current standard of research in bipolar disorder. These include the fragmentation of bipolar disorder into phases that are handled as being almost absolutely independent from each other, and thus the development of an overall therapeutic strategy on the basis of the existing evidence is very difficult. Trials are not always designed in a way that outcomes cover the most important aspects of bipolar disorder, and often the reporting of the results is biased and unsatisfactory. The data on combination treatments and high dosages are sparse, whereas they are common in real world practice.Conclusions:The workgroup endorses the full release of raw study data to the scientific community, and the development of uniform clinical trial standards (also including more realistic outcomes) and the reporting of results. The 2 large appendices summarize the results of this systematic review with regard to the areas of lack of knowledge where further focused research is necessary.

Dissemination of a Brief Psychoeducational Intervention for Bipolar Disorder in Community Mental Health Settings

Various efficacious psychosocial interventions for Bipolar Disorder (BD) share common elements, with psychoeducation being a main component. Recent treatment guidelines for BD recommend psychoeducation, especially when delivered in brief, cost-effective formats. Its format has several implications for the feasibility of its dissemination in the health care system. The Life Goals Program (LGP) is an evidence-based, cost-effective psychoeducational treatment for BD. Despite its demonstrated benefits for patients and the healthcare system, most patients do not have access to this type of treatment. The goal of this study is to examine the dissemination of the LGP and its effectiveness in three community mental health care centers in Quebec, Canada. A sample of 15 healthcare service providers received thorough training in the delivery of the LGP and delivered the treatment to 73 patients with BD. The treatment consisted of six 90-minute sessions described in the treatment manual with session six being repeated with a family member attending. Treatment integrity and clinical effectiveness were assessed with objective measures. The intervention was successfully implemented, with high rates of treatment fidelity and positive impacts on clinical outcomes. Patients demonstrated marked gains in knowledge about BD, increased acceptance of the illness, reductions in depressive symptoms and improvements in medication behaviors. Treatment effect sizes were moderate to large. Results show that the LGP can be successfully implemented in routine mental health settings given the brief format of the intervention, its proven cost effectiveness, and its less extensive training requirements.

Review of double mood stabilizer treatments for bipolar disorder in China

Background: Although treatment guidelines for bipolar disorder in many countries commonly include lithium carbonate joint with sodium valproate, this combination is not effective for all patients. Moreover, some adverse reactions related to this treatment, neurotoxicity and interaction with other drugs justify and call for a new reviewing of the issue. Methods: Evidence base for the interactions of combined drugs, the metabolic features, action mechanism, efficacy and side effects of these treatment combinations were reviewed. Considerable attention was given to the relationship of the mutual action of these drugs with their clinical efficacy but also their side effects. Results: The efficacy of combination therapy of lithium with valproate for treatment and prevention of mania were superior to monotherapy of lithium or valproate. Conclusion: Double mood stabilizer therapy is the best relative treatment for patients with bipolar disorder, especially mania and related episodes.

Lithium treatment and potential long-term side effects: a systematic review of the literature

Lithium is recommended by all treatment guidelines for bipolar disorder (BD) as a first-line maintenance treatment. However, the potential side effects and risks associated with long-term lithium use may at times make the implementation of these recommendations in daily practice challenging. The aim of the study is to review available literature on potential long-term side effects of lithium. A PubMed/Medline search was performed on papers dealing with long-term treatment with lithium and side effects. Articles published from January 1980 to February 2013 were selected. Long-term lithium treatment is associated with a reduced urinary concentrating ability, with subsequent polyuria and polidypsia and nephrogenic diabetes insipidus (in 10-40% of patients). Lithium also reduces glomerular filtration rate, and increases risk of renal failure, although the absolute risk is small (0.5% of patients). Lithium treatment is associated with significant higher TSH levels, with a 6-fold greater risk of hypothyroidism in lithium-treated than in control subjects. Less known is the increase of PTH and calcium levels induced by lithium. An exacerbation of psoriasis is also frequently associated with lithium treatment. Lithium remains a fundamental tool for the treatment of BD. Clinicians should know potential side effects (renal, endocrine and dermatological) associated with long-term treatment with lithium, for a correct management of the patient. A specialist referral is often necessary; the question is how to deal with long-term side effects more than whether or not withdrawing lithium. This decision should remain a psychiatrist's competence.

Dilemma for enhancing psychiatrists’ adherence to guideline (evidence)-based practice

Evaluation of: Glauser TA, Cerenzia W, Wiley S, Howson A, Thase M. Identifying psychiatrists’ practice patterns when managing depression in patients with bipolar I disorder: a descriptive study to inform education needs. Postgrad. Med. 125(1), 144–153 (2013).Bipolar disorder (BD) is a prevalent and chronic devastating disorder that is associated with considerable psychosocial and economic morbidity. However, its complexity in the clinical course and manifestation of bipolar disorder is still a significant barrier to accurate differential diagnosis from unipolar depression (UD), by which it is still underdiagnosed and undertreated in clinical practice. In community studies, first onset of BD is usually in the adolescent ages, and the occurrence of UD is usually its first clinical manifestation. In addition, reliable criteria for differentiating UD from BD along with validated treatment guidelines for BD are currently not sufficient or adequate, commonly resulting in misdiagnosis and mismanagement of both clinical conditions. Therefore, the study under evaluation results from clinician practice patterns in the real world will substantially enhance the current understanding on the actual situation and unmet needs for accurate and proper diagnosis and management of bipolar depression.

The relationship between use of antidepressants and resource utilization among patients with manic or mixed bipolar disorder episodes: Findings from a managed care setting

Treatment guidelines for bipolar disorder (BD) recommend the tapering of antidepressants (ADs) for patients with a recent acute manic or mixed episode. This study assessed rates of AD use and the association between such use and BD-related re-hospitalizations among patients with BD. Using the IMS LifeLink® Health Plan Claims Database from 1/1/2004 to 6/30/2007, we identified adults 18+ years of age with an acute psychiatric event ("index event"), defined as a hospitalization, emergency room visit, or physician visit, with a prescription for a new BD medication with a primary diagnosis of BD I mania (ICD-9-CM: 296.0x, 296.4x) or BD I mixed (ICD-9-CM: 296.6x). All patients were required to be eligible for the 12 months before index and during the 12-month post-index period, and have a BD-related hospitalization (any diagnosis of any BD subgroup) in the pre-index period. Patients with schizophrenia at any time during the study period were excluded. Study measures included: rates of AD use (minimum of 30 days of available AD therapy within 120 days after the index event) and the association of such use with post-index BD-related hospitalizations. 2126 patients met study criteria (mean age 44 years; 57% female; 53% BD I mania). 32% of all patients had AD use in the post-index period. Compared to BD I patients without AD use in the post-index period, those with AD use had 1.43 to 1.50 times the odds of being re-hospitalized for BD in the follow-up period. Other significant positive predictors included being female and presence of substance abuse. Administrative claims data do not provide information on symptoms, which may influence continuation of antidepressants. In this administrative claims database, nearly one-third of patients with BD I manic or mixed subgroups had AD use following an acute event. The positive association observed between AD use and re-hospitalization needs to be confirmed in clinical studies.

New treatment guidelines for acute bipolar mania: A critical review

A number of treatment guidelines for bipolar disorder have been published and updated in the last few years. They are aimed at providing a synthesis of the best available scientific knowledge, and their application to every-day work should be helpful to clinicians. The aim of this report is to critically review recent guidelines focusing on the treatment of manic/hypomanic and mixed episodes. Guidelines are quite heterogeneous in methodology and conclusions, but they all agree that the treatment of manic/hypomanic and mixed episodes should generally be initiated with a medication such as lithium (Li), valproate (VPA) or atypical antipsychotics (AAP), including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone as monotherapy. All guidelines agree on stopping ongoing antidepressant medication during mania. Combination therapy including Li or VPA with an AAP is suggested usually as second-line choice, sometimes as first-choice treatment for severe mania. Carbamazepine is mostly suggested as second line and not recommended in combination. Other antiepileptic drugs are not recommended for the treatment of mania, although lamotrigine may be maintained if it was prescribed previously for the prevention of depressive episodes. Main sources of discrepancies among guidelines include benefit-risk ratio issues (how much priority is given to efficacy over safety and tolerability), starting with combination versus monotherapy, and how to deal with treatments which are more experience-based than evidence-based (i.e.: electroconvulsive therapy).

The Clinical Management of Bipolar Disorder

To discuss the criteria used to diagnose the mood episodes that constitute bipolar disorder, the approach to the differential diagnosis of these presentations, and the evidence-based treatments that are currently available. A search for evidence-based guidelines for the diagnosis and treatment of adults with bipolar disorder was performed on May 5, 2010, using the National Guideline Clearinghouse database, the Agency for Healthcare Research and Quality Evidence Reports database, and the Cochrane Database of Systematic Reviews. In addition, a clinical query of the PubMed database (completed March 1, 2010) and searches of drug manufacturers' Web sites (for unpublished trials) were performed to identify randomized, controlled trials and meta-analyses evaluating strategies to treat resistant depression. Guidelines were selected based on data from randomized, controlled trials; meta-analyses; and well-conducted naturalistic trials that were published since 2005. Four evidence-based treatment guidelines for bipolar disorder were included. Three were published in 2009: those put forth as part of an Australian project, those of the British Association for Psychopharmacology, and those produced by the International Society for Bipolar Disorders and the Canadian Network for Mood and Anxiety Treatments. The most recent US guidelines are that of the Texas Implementation of Medication Algorithms project, last updated in 2005. Recommendations from all 4 guidelines were reviewed and are presented with a focus on using them to improve clinical care. The recommendations with the most agreement and highest level of clinical evidence were as follows: (1) mania should be treated first-line with lithium, divalproex, or an atypical antipsychotic medication; (2) mixed episodes should be treated first-line with divalproex or an atypical antipsychotic; (3) bipolar depression should be treated with quetiapine, olanzapine/fluoxetine combination, or lamotrigine; and (4) all patients should be offered group or individual psychoeducation. Additionally, recommendations for therapeutic drug monitoring are presented due to their importance for patient safety, particularly for the primary care physician, although these are based on consensus guidelines. Bipolar disorder is a lifelong illness that is complicated by high comorbidity and risk of poor health outcomes, making the primary care physician's role vital in improving patient quality of life. The management of acute mood episodes should focus first on safety, should include psychiatric consultation as soon as possible, and should begin with an evidence-based treatment that may be continued into the maintenance phase. Long-term management focuses on maintenance of euthymia, requires ongoing medication, and may benefit from adjunctive psychotherapy.

Mood stabilizers for patients with bipolar disorder: the state of the art

Bipolar disorder (BD) is a prevalent and disabling condition, often comorbid with other medical and psychiatric conditions and frequently misdiagnosed. International treatment guidelines for BD recommend the use of mood stabilizers – either in monotherapy or in association – as the gold standard in both acute and long-term therapy. Commonly used in the clinical practice of BD, mood stabilizers have represented an evolving field over the last few years. The concept of stabilization, in fact, has been stressed as the ultimate objective of the treatment of BD, given the chronic and recurrent nature of the illness, which accounts for its significant levels of impairment and disability. To date, different compounds are included within the broad class of mood stabilizers, with lithium, anticonvulsants and, more recently, atypical antipsychotics being the most representative agents. This article is aimed at providing an updated review of the available literature in relation to the role of mood stabilizers in BD, with particular emphasis on their mechanism of action, main clinical aspects and specific use in the different phases of BD treatment, according to the most recently published international treatment guidelines.

A Successful Effort to Improve Adherence to Treatment Guidelines for Bipolar Disorder

Smith, Thomas E.; Levine, Stewart B.; Hampel, JudithEditor(s): Hermann, Richard C. MD Author Information

P.2.e.017 Bipolar disorder treatment guidelines followed by Spanish psychiatrists. GAMEB Study

P.2.e.017 Bipolar disorder treatment guidelines followed by Spanish psychiatrists. GAMEB Study