The Clinical Management of Bipolar Disorder: A Review of Evidence-Based Guidelines

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Objective: 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.

Data Sources: 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a clinical query of the PubMed database (completed March 1, 2010) and searches of drug manufacturers’ Web sites (for unpublished trials) were performed to identify randomized, controlled trials and meta-analyses evaluating strategies to treat resistant depression.

Study Selection: Guidelines were selected based on data from randomized, controlled trials; meta-analyses; and well-conducted naturalistic trials that were published since 2005.

Data Extraction: 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.

Data Synthesis: 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.

Conclusions: 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.

Prim Care Companion CNS Disord 2011;13(4):doi:10.4088/PCC.10r01097

Submitted: October 14, 2010; accepted November 30, 2010.

Published online: July 14, 2011 (doi:10.4088/PCC.10r01097).

Corresponding author: Kevin R. Connolly, MD, Philadelphia VA Medical Center, Behavioral Health, 3800 Woodland Ave, Philadelphia, PA 19104 (

Prim Care Companion CNS Disord 2011;13(4):doi:10.4088/PCC.10r01097