| #### Table 12. Hierarchical rankings of first and second‐line treatments recommended for management of acute mania | |
| ##### First-line treatments: Monotherapies | |
| ###### Lithium | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 1 evidence. Prevention of mania during maintenance: level 1 evidence. Prevention of depression during maintenance: level 1 evidence. Acute depression: 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. Maintenance phase tolerability concerns: moderate impact on treatment selection. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Quetiapine | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 1 evidence. Prevention of mania during maintenance: level 1 evidence. Prevention of depression during maintenance: level 1 evidence. Acute depression: 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 depressive switch: limited impact on treatment selection. | |
| ###### Divalproex | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 1 evidence. Prevention of mania during maintenance: level 3 evidence. Prevention of depression during maintenance: level 2 evidence. Acute depression: level 2 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. Maintenance phase tolerability concerns: minor impact on treatment selection. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Asenapine | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 2 evidence. Prevention of mania during maintenance: level 2 evidence. Prevention of depression during maintenance: level 2 evidence. Acute depression: 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 depressive switch: limited impact on treatment selection. | |
| ###### Aripiprazole | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 2 evidence. Prevention of mania during maintenance: level 2 evidence. Prevention of depression during maintenance: no data; although monotherapies are listed above combination therapies in the hierarchy, combination therapies may be indicated as the preferred choice in patients with previous history of partial response to monotherapy and in those with psychotic mania or in situations where rapid response is desirable. Acute depression: level 1 negative 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. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Paliperidone(>6mg) | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 2 evidence. Prevention of mania during maintenance: level 2 evidence. Prevention of depression during maintenance: no data; although monotherapies are listed above combination therapies in the hierarchy, combination therapies may be indicated as the preferred choice in patients with previous history of partial response to monotherapy and in those with psychotic mania or in situations where rapid response is desirable. Acute depression: 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. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Risperidone | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 3 evidence. Prevention of mania during maintenance: level 3 evidence. Prevention of depression during maintenance: no data. Acute depression: 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. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Cariprazine | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: no data. Prevention of mania during maintenance: no data. Prevention of depression during maintenance: no data. Acute depression: 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 depressive switch: limited impact on treatment selection. | |
| ##### First-line treatments: Combination therapies | |
| ###### Quetiapine and Lithium/divalproex | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 1 evidence. Prevention of mania during maintenance: level 1 evidence. Prevention of depression during maintenance: level 1 evidence. Acute depression: level 4 evidence; no controlled trials; however, clinical experience suggests that it is a useful strategy. | |
| ####### 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. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Aripiprazole and Lithium/divalproex | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 2 evidence. Prevention of any mood episode during maintenance: level 2 evidence. Prevention of mania 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. Acute depression: level 4 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. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Risperidone and Lithium/divalproex | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 4 evidence. Prevention of mania during maintenance: level 4 evidence. Prevention of depression during maintenance: no data. Acute depression: level 4 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. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Asenapine and Lithium/divalproex | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 2 evidence. Prevention of any mood episode during maintenance: level 4 evidence. Prevention of mania during maintenance: level 4 evidence. Prevention of depression during maintenance: no data. Acute depression: level 4 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: minor impact on treatment selection. Risk of depressive switch: limited impact on treatment selection. | |
| ##### Second-line treatments: Combination therapies | |
| ###### Olanzapine | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 1 evidence. Prevention of mania during maintenance: level 1 evidence. Prevention of depression during maintenance: level 1 evidence. Acute depression: level 1 evidence; did not separate from placebo on core symptoms of depression. | |
| ####### 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. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Carbamazepine | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 2 evidence. Prevention of mania during maintenance: level 2 evidence. Prevention of depression during maintenance: level 2 evidence. Acute depression: level 3 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; divalproex and carbamazepine should be used with caution in women of childbearing age. Maintenance phase tolerability concerns: moderate impact on treatment selection. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Olanzapine and Lithium/divalproex | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 4 evidence. Prevention of mania during maintenance: level 4 evidence. Prevention of depression during maintenance: level 4 evidence. Acute depression: 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 impact on treatment selection. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Lithium and divalproex | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 2 evidence. Prevention of any mood episode during maintenance: level 2 evidence. Prevention of mania during maintenance: level 2 evidence. Prevention of depression during maintenance: no data. Acute depression: 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. Maintenance phase tolerability concerns: moderate impact on treatment selection. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Ziprasidone | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: level 3 evidence. Prevention of mania during maintenance: level 3 evidence. Prevention of depression during maintenance: no data. Acute depression: level 1 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. Maintenance phase tolerability concerns: minor impact on treatment selection. Risk of depressive switch: limited impact on treatment selection. | |
| ###### Haloperidol | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 1 evidence. Prevention of any mood episode during maintenance: no data. Prevention of mania during maintenance: level 4 evidence. Prevention of depression during maintenance: level 4 negative evidence. Acute depression: 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. Risk of depressive switch: moderate impact on treatment selection. | |
| ###### ECT | |
| ####### Level of evidence by phase of treatment | |
| Acute mania: level 3 evidence. Prevention of any mood episode during maintenance: level 4 evidence. Prevention of mania during maintenance: level 4 evidence. Prevention of depression during maintenance: level 4 evidence. Acute depression: level 4 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 depressive switch: limited impact on treatment selection. | |