Table 5 Current status of depression in bipolar disorder

Depression in bipolar disorder (BD) is the major residual psychiatric morbidity with available treatments, accounting for three-quarters of the 40–50% long-term time-ill

Unresolved morbidity, and especially depression, is associated with excess medical morbidity, including metabolic syndrome and cardiovascular disease, with increased mortality

Suicide risk in BD is similar in types I and II BD, greater than in most other psychiatric disorders, ca. 20-times above general population rates, and strongly associated with depression, especially with agitation (mixed-dysphoric states), and in the days–weeks following hospital discharge

Predicting suicide in BD clinically is limited regarding individuals and timing

Treatments proposed to prevent suicidal behavior in BD include lithium, clozapine, and possibly ketamine and psychotherapies, which all require further study

Therapeutics of bipolar depression is far less well developed than for nonbipolar major depression, probably reflecting lack of recognition of differences between bipolar and unipolar depression

The short-term value and safety of antidepressant treatment for bipolar depression remains controversial, and long-term value remains virtually untested; it is best avoided with ongoing dysphoric agitation or mixed features

Some modern antipsychotics are effective in bipolar depression short-term; lithium and lamotrigine have modest prophylactic value long-term but are not adequately tested short-term; other anticonvulsant mood-stabilizers have very limited evidence of short- or long-term efficacy in bipolar depression

All available treatments for bipolar depression have risks of adverse metabolic or neurological effects; valproate and carbamazepine are also highly teratogenic