Based on available clinical evidence, an international group developed consensus guidelines for the treatment of bipolar I depression and published them in the April 2004 issue of the Journal of Clinical Psychiatry.

"In the treatment of bipolar disorder, the guidelines available for treating mania are fairly standard worldwide," write Joseph R. Calabrese, MD, from Case Western Reserve University School of Medicine in Cleveland, Ohio, and colleagues. "However, guidelines for treating bipolar depression vary, sometimes substantially, from country to country."

Barriers to effective treatment of bipolar I depression include unrecognized bipolar I depression, routine use of antidepressant therapy for either unipolar or bipolar depression despite the availability of more specific treatment for bipolar depression, and common misconceptions about bipolar depression. The authors stress that bipolar disorder is a chronic illness requiring lifelong treatment, and that the entire illness, rather than just acute episodes, must be treated to ensure success.

Based on the quality of available data, the authors classified evidence for each agent used to treat bipolar depression. Drugs meeting category 1 evidence had randomized, placebo-controlled trials in acute bipolar depression and in long-term treatment of both depression and mania. Category 2 evidence consisted of randomized, placebo-controlled trials in acute bipolar depression or in long-term treatment of either depression or mania, while category 3 evidence had randomized controlled trials in any phase of bipolar disorder treatment.

Recognizing that long-term safety and efficacy data should affect medication selection, the authors developed an algorithm for acute treatment of bipolar I depression. First-line treatment should be lithium or lamotrigine (category 1), or olanzapine as monotherapy or in combination with fluoxetine (category 2). Patients responding to first-line treatment should continue it for the long term.

Those with breakthrough mania should have first-line treatment optimized. Other options are to add lithium or olanzapine (category 1), valproate or risperidone (category 2), or aripiprazole, ziprasidone, quetiapine, or clozapine (category 3).

Patients failing first-line treatment who have continued depressive symptoms should be treated based on other clinical features. Those with nonrapid cycling should have first-line treatment optimized, followed by continuation of two first-line treatments or addition of an antidepressant other than a tricyclic or monoamine oxidase inhibitor. After optimizing first-line treatment, those with rapid cycling should have added valproate or olanzapine. Psychotic patients should have added olanzapine alone or combined with fluoxetine, or electroconvulsive therapy (ECT).

"Clinicians should consider the individual patient when deciding what treatment to use in bipolar depression as well as deciding what treatment to use for patients whose response to treatment is inadequate," the authors write. "All patients with bipolar disorder should be treated with psychological treatments in addition to any pharmacological treatment."

GlaxoSmithKline supported the consensus meeting at which the guidelines were developed.

J Clin Psychiatry. 2004;65:000-000

Bipolar depression is often underdiagnosed or misdiagnosed as unipolar depression. Antidepressant monotherapy continues to be the most common treatment for bipolar I depression throughout the world despite the lack of evidence showing efficacy, according to a study by Ghaemi and colleagues, published in the July 2001 issue of the Journal of Clinical Psychiatry. Indeed, antidepressants, alone or in combination with lithium, may induce rapid cycling or mania in bipolar I patients. A study by Gyulai and colleagues, published in the July 2003 issue of Neuropsychopharmacology, showed that antidepressant monotherapy is significantly less effective at preventing depressive relapse than an antidepressant-mood stabilizer combination. Treatment guidelines such as those from the American Psychiatric Association now recommend avoiding antidepressant monotherapy for bipolar depression.

The International Consensus Group on Bipolar I Depression met in December 2003 to develop international treatment guidelines based on currently available evidence from randomized, placebo-controlled, double-blinded clinical trials of pharmacotherapy. The group agreed that bipolar disorder is a chronic condition that requires lifelong treatment, and that both acute and long-term safety and efficacy should be considered when selecting first-line treatments. In addition, the group stressed that therapy should be tailored to individual patient needs and response to previous therapy.