Treatment of Bipolar Depression

Bipolar disorder consists of depressive episodes of low mood, difficulty in concentration and work, poor sleep, and poor appetite, as well as distinct manic episodes of expansive mood, pressured speech, overactivity, sexual excesses, aggressiveness, and little need for sleep; both types of episode may last for weeks or months. The primary goal of treatment is the prevention of these episodes with the use of mood stabilizers such as lithium, valproate, carbamazepine, and lamotrigine and some of the new atypical antipsychotic drugs such as olanzapine or quetiapine. However, when prophylaxis fails and a depressive or manic episode occurs, questions of appropriate treatment arise. Moreover, many patients cease to comply with the regimen of prophylactic mood stabilizers, go on to have a manic or depressive episode, and then present for treatment.

Conservative treatment of a depressive episode in a patient with bipolar disorder would be to initiate the use of a mood stabilizer if the patient is not taking one or to increase the dose or add a second mood stabilizer if the patient is already taking one. A more aggressive clinical approach would be to add an antidepressant to the mood stabilizer. Depressive episodes in patients with bipolar disorder are problematic, since families are often relieved that the patients are not manic and are willing to allow conservative treatment, but the patients have symptoms that are subjectively worse during depressive episodes than during manic episodes and often request aggressive treatment. The clinical phenomenology of bipolar depression is similar to that of unipolar major depression. Thus, it has seemed reasonable to assume that antidepressants that are effective in treating unipolar major depression would be effective in treating bipolar depression as well.

Two European reviews of published studies have shown that antidepressant treatment can be highly beneficial for bipolar depression, with little risk of the induction of mania. Traditionally, American psychiatrists have assumed that antidepressants are effective for bipolar depression but carry a risk of inducing mania. Therefore, in the study by Sachs et al. in this issue of the Journal — the largest study of its kind to date — it comes as a surprise that the addition of antidepressants to one or more mood stabilizers in the treatment of bipolar depression neither improved the depressive symptoms nor increased the risk of a switch to mania. These findings widen the gap between North America and Europe regarding the efficacy of antidepressants in the treatment of bipolar disorder but narrow the gap regarding the danger of mania.

The study by Sachs et al. is part of a large effectiveness study, funded by the National Institute of Mental Health, that differs from classic efficacy studies. Called the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), it is carried out in the community with a sequential design and a large patient population that can be randomly assigned to different treatment groups at various stages in their illness, according to the principle of equipoise. The STEP-BD investigators enrolled 4360 patients; 2689 patients had at least one major depressive episode at some point during the program. Of these, only 366 were enrolled and randomly assigned to a group in the study by Sachs et al.