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#### Table 14. Hierarchical rankings of first and second‐line treatments recommended for management of acute bipolar I depression ##### First-line treatments ###### Quetiapine ####### Level of evidence by phase of treatment Acute depression: level 1 evidence. Prevention of any mood episode during maintenance: level 1 evidence. Prevention of depression during maintenance: level 1 evidence. Prevention of mania during maintenance: level 1 evidence. Acute mania: level 1 evidence. ####### Considerations for treatment selection Acute phase safety concerns: minor impact on treatment selection. Acute phase tolerability concerns: moderate impact on treatment selection. Maintenance phase safety concerns: moderate impact on treatment selection. Maintenance phase tolerability concerns: moderate impact on treatment selection. Risk of manic / hypomanic switch: limited impact on treatment selection. ###### Lurasidone and Lithium/divalproex ####### Level of evidence by phase of treatment Acute depression: level 1 evidence. Prevention of any mood episode during maintenance: level 3 evidence; trend for superiority on the primary efficacy measure, hence the lower rating. Prevention of depression during maintenance: level 3 evidence; effective in those with an index episode of depression. Prevention of mania during maintenance: level 4 evidence; negative data from the trial are probably due to methodological issues; rating based on expert opinion. Acute mania: no data. ####### Considerations for treatment selection Acute phase safety concerns: minor impact on treatment selection. Acute phase tolerability concerns: moderate impact on treatment selection. Maintenance phase safety concerns: moderate impact on treatment selection; divalproex and carbamazepine should be used with caution in women of childbearing age. Maintenance phase tolerability concerns: moderate / limited impact on treatment selection. Risk of manic / hypomanic switch: limited impact on treatment selection. ###### Lithium ####### Level of evidence by phase of treatment Acute depression: level 2 evidence. Prevention of any mood episode during maintenance: level 1 evidence. Prevention of depression during maintenance: level 1 evidence. Prevention of mania during maintenance: level 1 evidence. Acute mania: no data. ####### Considerations for treatment selection Acute phase safety concerns: minor impact on treatment selection. Acute phase tolerability concerns: minor impact on treatment selection. Maintenance phase safety concerns: moderate impact on treatment selection. Maintenance phase tolerability concerns: moderate impact on treatment selection. Risk of manic / hypomanic switch: limited impact on treatment selection. ###### Lamotrigine ####### Level of evidence by phase of treatment Acute depression: level 2 evidence. Prevention of any mood episode during maintenance: level 1 evidence. Prevention of depression during maintenance: level 1 evidence. Prevention of mania during maintenance: level 2 evidence. Acute mania: level 1 negative evidence. ####### Considerations for treatment selection Acute phase safety concerns: moderate impact on treatment selection. Acute phase tolerability concerns: limited impact on treatment selection. Maintenance phase safety concerns: limited impact on treatment selection. Maintenance phase tolerability concerns: limited impact on treatment selection. Risk of manic / hypomanic switch: limited impact on treatment selection. ###### Lurasidone ####### Level of evidence by phase of treatment Acute depression: level 2 evidence. Prevention of any mood episode during maintenance: level 4 evidence. Prevention of depression during maintenance: level 4 evidence. Prevention of mania during maintenance: level 4 evidence. Acute mania: no data. ####### Considerations for treatment selection Acute phase safety concerns: limited impact on treatment selection. Acute phase tolerability concerns: minor impact on treatment selection. Maintenance phase safety concerns: limited impact on treatment selection. Maintenance phase tolerability concerns: minor impact on treatment selection. Risk of manic / hypomanic switch: limited impact on treatment selection. ###### Lamotrigine(adj) ####### Level of evidence by phase of treatment Acute depression: level 2 evidence. Prevention of any mood episode during maintenance: level 4 evidence. Prevention of depression during maintenance: level 4 evidence. Prevention of mania during maintenance: level 4 evidence. Acute mania: level 4 negative evidence. ####### Considerations for treatment selection Acute phase safety concerns: moderate impact on treatment selection. Acute phase tolerability concerns: minor impact on treatment selection. Maintenance phase safety concerns: moderate impact on treatment selection. Maintenance phase tolerability concerns: moderate impact on treatment selection. Risk of manic / hypomanic switch: limited impact on treatment selection. ##### Second-line treatments ###### Divalproex ####### Level of evidence by phase of treatment Acute depression: level 2 evidence. Prevention of any mood episode during maintenance: level 1 evidence. Prevention of depression during maintenance: level 2 evidence. Prevention of mania during maintenance: level 3 evidence. Acute mania: level 1 evidence. ####### Considerations for treatment selection Acute phase safety concerns: limited impact on treatment selection. Acute phase tolerability concerns: minor impact on treatment selection. Maintenance phase safety concerns: moderate impact on treatment selection; divalproex and carbamazepine should be used with caution in women of childbearing age. Maintenance phase tolerability concerns: minor impact on treatment selection. Risk of manic / hypomanic switch: limited impact on treatment selection. ###### SSRIs/bupropion(adj) ####### Level of evidence by phase of treatment Acute depression: level 1 evidence. Prevention of any mood episode during maintenance: no data. Prevention of depression during maintenance: level 4 evidence. Prevention of mania during maintenance: no data. Acute mania: no data. ####### Considerations for treatment selection Acute phase safety concerns: limited impact on treatment selection. Acute phase tolerability concerns: minor impact on treatment selection. Maintenance phase safety concerns: limited impact on treatment selection. Maintenance phase tolerability concerns: minor impact on treatment selection. Risk of manic / hypomanic switch: minor impact on treatment selection. ###### ECT ####### Level of evidence by phase of treatment Acute depression: level 4 evidence. Prevention of any mood episode during maintenance: level 4 evidence. Prevention of depression during maintenance: level 4 evidence. Prevention of mania during maintenance: level 4 evidence. Acute mania: level 3 evidence. ####### Considerations for treatment selection Acute phase safety concerns: minor impact on treatment selection. Acute phase tolerability concerns: moderate impact on treatment selection. Maintenance phase safety concerns: minor impact on treatment selection. Maintenance phase tolerability concerns: moderate impact on treatment selection. Risk of manic / hypomanic switch: limited impact on treatment selection. ###### Cariprazine ####### Level of evidence by phase of treatment Acute depression: level 1 evidence. Prevention of any mood episode during maintenance: no data. Prevention of depression during maintenance: no data. Prevention of mania during maintenance: no data. Acute mania: level 1 evidence. ####### Considerations for treatment selection Acute phase safety concerns: limited impact on treatment selection. Acute phase tolerability concerns: minor impact on treatment selection. Maintenance phase safety concerns: limited impact on treatment selection. Maintenance phase tolerability concerns: limited impact on treatment selection. Risk of manic / hypomanic switch: limited impact on treatment selection. ###### Olanzapine-fluoxetine ####### Level of evidence by phase of treatment Acute depression: level 2 evidence. Prevention of any mood episode during maintenance: no data. Prevention of depression during maintenance: no data. Prevention of mania during maintenance: no data. Acute mania: no data. ####### Considerations for treatment selection Acute phase safety concerns: minor impact on treatment selection. Acute phase tolerability concerns: moderate impact on treatment selection. Maintenance phase safety concerns: significant impact on treatment selection. Maintenance phase tolerability concerns: minor impact on treatment selection. Risk of manic / hypomanic switch: minor impact on treatment selection. |