#### 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.