Inpatient or outpatient The risk of suicide/self-injury is highest during bipolar depression, with approximately 15-19% of patients with bipolar disorder committing suicide. Therefore, important factors in deciding whether a patient should be hospitalized or treated on an outpatient basis include the risk of suicide, severity of depression, and the availability of psychosocial support. First-line treatment For unmedicated bipolar depressed patients, lithium, quetiapine or lamotrigine monotherapy should be considered. Lithium blood levels should be maintained at ≥0.8 mmol/L to be effective. In clinical practice, lithium or valproate is often combined with bupropion or 5-HT antidepressants and is also appropriate for some bipolar depression. However, antidepressants are not indicated in patients with a history of rapid cycling or a history of severe mania unless both first- and second-line treatment options are ineffective. Olanzapine in combination with a 5-HT antidepressant is effective, especially in bipolar depression with psychotic symptoms. If a patient experiences a depressive episode during first-line medication, do not readily change the treatment regimen and adjust the dose for observation as appropriate, e.g., a relapse during valproate treatment should still be observed, as there are studies confirming its effectiveness. However, if a relapse occurs during treatment with atypical antipsychotics (except quetiapine), a revised treatment regimen should be considered with reference to the treatment flow. Second-line treatment In cases where monotherapy with two or more first-line treatment drugs is unsatisfactory or poor, a combination between first-line drugs or a combination of first- and second-line drugs may be considered. In the case of lamotrigine combined with sodium valproate, the former must be given in minimal dose increments to avoid serious adverse effects such as skin rash. Modified electroconvulsive therapy (MECT) Although evidence from controlled studies is lacking, open studies and clinical experience suggest that MECT or ECT for bipolar depression is highly effective and has a faster onset of action than pharmacotherapy. Although MECT is classified as a third-line treatment because of its acceptability and side effects, it should be an early treatment option for patients with psychotic depression, severe and suicidal risk, food and drink refusal and medical risk (poor somatic condition), and in the first trimester of pregnancy. There are no controlled studies of psychosocial treatment alone in the acute treatment of bipolar depression; however, some strategies of psychosocial treatment are often used in combination with pharmacotherapy to manage bipolar depression. The combination of cognitive behavioral therapy (CBT), interpersonal and social rhythm therapy, and family therapy can help improve outcomes. Combinations should be considered if available, especially in patients with recurrent bipolar depression.