The efficacy and safety of lurasidone monotherapy in patients with bipolar I depression, including those with or without rapid cycling, have not been thoroughly explored in previous research. To address this gap, we conducted a subgroup analysis based on data pooled from two randomized, double-blind, placebo-controlled trials, each lasting for six weeks.
Lurasidone, administered at doses of 20-60 mg/day or 80-120 mg/day, was the focus of these investigations. The primary outcome assessed was the mean change from baseline to week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Additionally, safety evaluations included monitoring the number of treatment-emergent adverse events (TEAEs) and laboratory assessments.
Out of the 1024 patients who were part of the randomized trials, 85 were identified as experiencing rapid cycling. The analysis of the mean change in MADRS total score showed that for patients without rapid cycling and those with rapid cycling, respectively, the following results were observed:
In the lurasidone 20-60 mg/day group: -14.8 (effect size = 0.47) and -12.8 (effect size = 0.04) In the lurasidone 80–120 mg/day group: -14.3 (effect size = 0.41) and -13.0 (effect size = 0.02). In the placebo group: -10.6 and -13.3.
Notably, patients without rapid cycling demonstrated significant improvements in depressive symptoms compared to those receiving a placebo in both the lurasidone 20-60 mg/day and 80-120 mg/day dosage groups.
Safety assessments revealed that akathisia was the most common TEAE in both lurasidone groups, with treatment-emergent mania being reported only in a small number of patients with both rapid cycling and non-rapid cycling patterns.
It’s essential to acknowledge the limitations of this study. This analysis was conducted post-hoc and based on short-term trials. Additionally, the original trials excluded patients with a history of experiencing eight or more cycles in the past year.
In patients with non-rapid cycling bipolar depression, lurasidone monotherapy exhibited a significant improvement in depressive symptoms when compared to a placebo, irrespective of the dosage (20-60 mg/day or 80-120 mg/day) administered.
However, in patients with rapid cycling, the results were not as definitive. Lurasidone doses showed reductions in depressive symptom scores from baseline, but these improvements did not reach statistical significance. This outcome could be attributed to the high levels of improvement observed in the placebo group and the relatively small sample size of patients with rapid cycling.
This research provides valuable insights into the potential benefits of lurasidone monotherapy in treating bipolar I depression, particularly in patients without a history of rapid cycling.
Despite some limitations, these findings offer a stepping stone for further exploration of treatment options and underscore the need for more extensive studies to better understand the complexities of bipolar depression management. These insights can guide healthcare professionals in making more informed decisions regarding the use of lurasidone in specific patient populations.
Journal Reference
Kato M, Masuda T, Sano F, Kato T. The efficacy and safety of lurasidone in bipolar I depression with and without rapid cycling: A pooled post-hoc analysis of two randomized, placebo-controlled trials. J Affect Disord. 2023 Sep 15;337:150-158. doi: 10.1016/j.jad.2023.05.065.
