Lithium and lamotrigine for the treatment of bipolar II disorder - a systematic review and meta-analysis of randomized trials

OBJECTIVES: This systematic review and meta-analysis aimed to synthesize the evidence from randomized trials of lithium, lamotrigine, and placebo for the treatment of bipolar II disorder (BDII) in terms of bipolar II depression, hypomania, and maintenance treatment.

METHODS: A literature search was performed 20th November 2024 across PubMed, Embase and PsycINFO, and grey literature for studies of lithium, lamotrigine, and placebo in adults with BDII, across illness phases. Primary outcomes were efficacy and tolerability. We conducted random-effects pair-wise meta-analysis to provide a summary measure of effect, assessed the risk of bias, and assessed the certainty of the evidence using the GRADE framework.

RESULTS: Our search yielded 2326 records, including 10 randomized trials comprising 645 patients with BDII. The evidence was very uncertain regarding lithium's effect on the risk of new affective episodes, regardless of polarity, compared with placebo (RR 0.86, 95 % CI [0.66, 1.11], I2 = 0 %, four studies, very low certainty evidence). A quantitative synthesis could not be conducted to compare lamotrigine and placebo. The evidence was very uncertain regarding the effect of lithium on depression severity compared with lamotrigine (mean HAMD17 difference: 1.27, 95 % CI [-3.84, 6.38], I2 = 0 %, two studies, very low certainty evidence). The overall risk of bias was of 'some concern' for 84 % of outcomes assessed. For all outcomes, the certainty of the evidence was graded 'very low'.

CONCLUSION: The evidence for lithium and lamotrigine in treating BDII is scarce, and the certainty of the evidence is very low. Large, well-conducted RCTs of patients with BDII are needed.