Psychopharmacotherapy in Bipolar Depression, Present and Future

Jeong, Jong Hyun; Woo, Young Seop; Bahk, Won Myong

Abstract

This article reviews the characteristics and major pharmacological treatment modalities of bipolar depression, which is distinguished from unipolar depression by etiologic differences, symptomatic features, clinical courses, and treatment responses. Bipolar depression is often disabling and very challenging to treat. In acute and prophylactic phases, mood stabilizers such as lithium, divalproex, and lamotrigine are used as first-line treatment, unless the patient is psychotic or markedly dysfunctional. Carbamazepine and oxcarbazepine can be used as a second-line treatment or in a combination regimen. Depressive episodes that do not respond to mood stabilizers, as well as relapsing episodes despite prophylactic therapy, justify treatment with antidepressants. Many clinicians also advocate the early use of antidepressants and antipsychotics when depressive episodes are severe or psychotic. Selective serotonin reuptake inhibitors and bupropion are considered the first choices for use in combination with a mood stabilizer. Bupropion in particular yields stability against manic switches or cycle acceleration. Traditionally, clinicians have used antipsychotics as a combination option when treating patients with bipolar depression who exhibit psychotic features. However, extensive and well controlled recent studies have shown that atypical antipsychotics such as quetiapine, olanzapine, and an olanzapine/fluoxetine combination can yield therapeutic efficacy and good tolerability for treating bipolar depression with or without psychotic features. In particular, a randomized controlled trial (RCT) using quetiapine monotherapy to treat patients with bipolar depression yielded significantly reduced depressive symptomatology. Other atypical antipsychotics such as amisulpride, aripirazole, risperidone, and ziprasidone have yielded antidepressive efficacy, but no RCT trials have been conducted on patients with bipolar depression. Some preliminary studies have shown that newly developed agents such as dopamine agonist, agomelatine, riluzole, mefepristone, and uridine effectively improve mood symptoms among patients with bipolar depression. More extensive clinical trials are needed.