What is the first-line combination therapy for bipolar I disorder with depressive features?

The first-line combination therapy for bipolar I disorder with depressive features includes using either lithium or valproic acid in conjunction with lamotrigine or atypical antipsychotics such as aripiprazole or risperidone. This approach draws upon the mood-stabilizing effects of lithium or valproic acid to manage manic symptoms while addressing depressive episodes with medications known for their efficacy in treating bipolar depression.

Lithium is well-established as a mood stabilizer and has been effective in preventing both mania and depressive episodes in bipolar disorder. Valproic acid serves a similar purpose, especially for mood stabilization during acute mania. Lamotrigine, on the other hand, has demonstrated specific benefits in the depressive phases of bipolar disorder, making it a key addition to the treatment regimen for those experiencing depressive features. The atypical antipsychotics mentioned, such as aripiprazole and risperidone, can help manage acute manic or mixed episodes and have shown some utility in treating depressive symptoms in the context of bipolar disorder.

In contrast, a single agent like lithium alone or other combinations like valproic acid plus lamotrigine do not comprehensively address both the manic and depressive aspects of bipolar I disorder as effectively as the