Antidepressants for Bipolar Disorder

According to DSM-IV diagnostic criteria, bipolar disorder (bipolar affective disorder, manic-depressive disorder) is characterized by marked mood swings between mania (mood elevation) and depression. The essential feature of bipolar I disorder (BDI) is a clinical course that is defined by the occurrence of 1 or more manic or mixed episodes; the essential feature of bipolar II disorder (BDII) is a clinical course that is defined by the occurrence of 1 or more major depressive episodes accompanied by at least 1 hypomanic episode. As such, bipolar disorder can cause significant personal distress and social dysfunction. Bipolar disorder has been subdivided in several ways, but classically there are 2 clinical categories of the disorder. BDI is characterized by the occurrence of 1 or more manic or mixed episodes (mixed episode means that symptoms of mania and depression are present at the same time). Often individuals with BDI have also had 1 or more major depressive episodes. Episodes of substance-induced mood disorder (caused by the direct effects of a medication, other somatic treatments for depression, drug abuse, or toxin exposure) or of mood disorder caused by a general medical condition are not considered when making a diagnosis of bipolar disorder. By contrast, BDII is diagnosed when depression is interspersed with less severe episodes of elevated mood that do not lead to dysfunction or disability (hypomania). Although individuals with BDI can return to a fully functional level between episodes, some continue to display mood lability and interpersonal or occupational difficulties. Manic symptoms are the hallmark of the illness and can represent a real medical emergency. However, bipolar depression is often much more clinically significant.1 Depression was the third leading cause of burden among all diseases in 2002, and it is expected to rise in the next 20 years.2 Evidence suggests that depressive episodes and symptoms are equal to or more disabling than corresponding levels of manic or hypomanic symptoms and that only subsyndromal depressive symptoms (and not subsyndromal manic or hypomanic symptoms) are associated with significant impairment in patients with bipolar disorder.3 This scenario highlights the need for effectively treating bipolar depression. Although antidepressant drugs remain the mainstay of treatment for unipolar major depression in both primary and secondary care settings,4 the evidence to support antidepressant treatment for bipolar depression is limited and increasingly controversial—especially now that evidence is available for alternative medications, including quetiapine and lamotrigine.5 Apart from the limited evidence, a key problem with antidepressants is the potential for increasing the risk of iatrogenic episodes of elevated mood. This is the reason many reviews and guidelines for bipolar depression have recommended the use of a mood stabilizer (usually lithium or valproate) rather than an antidepressant as the first-line treatment for bipolar depression.6,7 Antidepressants are advised only as second-line treatment and always with a concurrent mood stabilizer to prevent switching to mania. However, in real-world clinical practice, antidepressants are still frequently