| #### Table 17. Hierarchical rankings of first‐ and second‐line treatments recommended for maintenance treatment in bipolar disorder | |
| ##### First-line treatment | |
| ###### Lithium | |
| ####### Level of evidence by phase of treatment | |
| 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 Depression: level 2 evidence. Acute Mania: level 1 evidence. | |
| ####### 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. | |
| ###### Quetiapine | |
| ####### Level of evidence by phase of treatment | |
| 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 Depression: 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. | |
| ###### Lamotrigine | |
| ####### Level of evidence by phase of treatment | |
| 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 Depression: level 1 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. | |
| ###### Asenapine | |
| ####### Level of evidence by phase of treatment | |
| Prevention of any mood episode during maintenance: level 2 evidence. Prevention of depression during maintenance: level 2 evidence. Prevention of mania during maintenance: level 2 evidence. Acute Depression: 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: minor impact on treatment selection. | |
| ###### Quetiapine + Lithium/divalproex | |
| ####### Level of evidence by phase of treatment | |
| 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 Depression: level 4 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: significant impact on treatment selection; divalproex and carbamazepine should be used with caution in women of childbearing age. Maintenance phase tolerability concerns: moderate impact on treatment selection. | |
| ###### Aripiprazole + Lithium/divalproex | |
| ####### Level of evidence by phase of treatment | |
| Prevention of any mood episode during maintenance: level 2 evidence. Prevention of depression during maintenance: no data; did not separate from placebo in those with index mania; no studies available in index depression. Prevention of mania during maintenance: level 2 evidence. Acute Depression: level 4 evidence. Acute Mania: level 2 evidence. | |
| ####### 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; divalproex and carbamazepine should be used with caution in women of childbearing age. Maintenance phase tolerability concerns: moderate impact on treatment selection. | |
| ###### Aripiprazole | |
| ####### Level of evidence by phase of treatment | |
| Prevention of any mood episode during maintenance: level 2 evidence. Prevention of depression during maintenance: no data; did not separate from placebo in those with index mania; no studies available in index depression. Prevention of mania during maintenance: level 2 evidence. Acute Depression: level 1 negative 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: limited impact on treatment selection. Maintenance phase tolerability concerns: minor impact on treatment selection. | |
| ###### Aripiprazole OM | |
| ####### Level of evidence by phase of treatment | |
| Prevention of any mood episode during maintenance: level 2 evidence. Prevention of depression during maintenance: no data; did not separate from placebo in those with index mania; no studies available in index depression. Prevention of mania during maintenance: level 2 evidence. Acute Depression: 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. | |
| ##### Second-line treatments | |
| ###### Olanzapine | |
| ####### Level of evidence by phase of treatment | |
| 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 Depression: level 1 evidence; did not separate from placebo on core symptoms of depression. 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: significant impact on treatment selection. Maintenance phase tolerability concerns: moderate impact on treatment selection. | |
| ###### Risperidone LAI | |
| ####### Level of evidence by phase of treatment | |
| Prevention of any mood episode during maintenance: level 1 evidence. Prevention of depression during maintenance: no data; did not separate from placebo in those with index mania; no studies available in index depression. Prevention of mania during maintenance: level 1 evidence. Acute Depression: 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: minor impact on treatment selection. Maintenance phase tolerability concerns: moderate impact on treatment selection. | |
| ###### Risperidone LAI (adj) | |
| ####### Level of evidence by phase of treatment | |
| Prevention of any mood episode during maintenance: level 2 evidence. Prevention of depression during maintenance: level 4 evidence. Prevention of mania during maintenance: level 2 evidence. Acute Depression: 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: moderate impact on treatment selection. | |
| ###### Carbamazepine | |
| ####### Level of evidence by phase of treatment | |
| Prevention of any mood episode during maintenance: level 2 evidence. Prevention of depression during maintenance: level 2 evidence. Prevention of mania during maintenance: level 2 evidence. Acute Depression: level 3 evidence. Acute Mania: level 1 evidence. | |
| ####### Considerations for treatment selection | |
| Acute phase safety concerns: moderate impact on treatment selection. Acute phase tolerability concerns: moderate impact on treatment selection. Maintenance phase safety concerns: minor impact on treatment selection; divalproex and carbamazepine should be used with caution in women of childbearing age. Maintenance phase tolerability concerns: moderate impact on treatment selection. | |
| ###### Paliperidone (>6 mg) | |
| ####### Level of evidence by phase of treatment | |
| Prevention of any mood episode during maintenance: level 2 evidence. Prevention of depression during maintenance: no data; did not separate from placebo in those with index mania; no studies available in index depression. Prevention of mania during maintenance: level 2 evidence. Acute Depression: 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: minor impact on treatment selection. Maintenance phase tolerability concerns: moderate impact on treatment selection. | |
| ###### Lurasidone + Lithium/divalproex | |
| ####### Level of evidence by phase of treatment | |
| 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. Acute Depression: level 2 evidence. 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. | |
| ###### Ziprasidone + Lithium/divalproex | |
| ####### Level of evidence by phase of treatment | |
| Prevention of any mood episode during maintenance: level 2 evidence. Prevention of depression during maintenance: no data; did not separate from placebo in those with index mania; no studies available in index depression. Prevention of mania during maintenance: level 2 evidence. Acute Depression: level 3 negative evidence. Acute Mania: level 2 negative evidence. | |
| ####### Considerations for treatment selection | |
| Acute phase safety concerns: moderate 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: minor impact on treatment selection. | |