| #### 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. | |