#### 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.