Table 3.

Summary of Quality of Evidence for Pharmacotherapy for Bipolar II Depression and Implications for Clinical Practice

Medication	Rating of Quality of Evidence	Implications for Treatment of Bipolar II Depression
Quetiapine	Type A: Pooled data from 2 large studies support its efficacy	Consider as a first line option
Lamotrigine	Type A: Very small effect size when used as monotherapy in 5 individual RCTs; modest advantage over placebo when examined in “meta-regression;” suggestion of advantage over placebo when used as augmentation strategy	Consider as a second line option both monotherapy and as an augmentation strategy
Lithium	Type B: Single positive open-label trial and historical clinical experience	Consider as a second line option
Antidepressants/Selective serotonin reuptake inhibitors (SSRI)	Type B: Preliminary results of open-label studies of antidepressants as monotherapy are promising; controlled trials of antidepressants as augmentation strategy show no advantage over placebo	Consider SSRI monotherapy as a second line option; antidepressants as a group may have limited utility as an augmentation strategy, although further testing of individual agents is indicated
Pramipexole	Type B: One small RCT suggest utility as augmentation strategy	Consider pramipexole as a second line augmentation strategy
Valproate	Not established	Inadequate data
Modafinil	Adjunctive treatment was associated with improvement in a mixed BP I/II cohort, but no clear signal for BP II subjects emerged	Inadequate data
Omega-3 Fatty Acids	A small number of individuals with BP II were included in two large RCTs but were not examined separately.	Inadequate data; available information is conflicting about its benefit as an add-on treatment in mixed BP I/II samples.