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#### 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. |