Akbarzadeh Farzad, Talaei Andisheh, Nematy Mohsen, Ganji Dina, Ebrahimi Alireza, Talaei Ali
Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Faculty of Biotechnology, Tehran University, Tehran, Iran.
Brain Behav. 2025 Apr;15(4):e70432. doi: 10.1002/brb3.70432.
Drug resistance poses a formidable challenge in managing acute manic episodes in bipolar I disorder, leading to suboptimal treatment outcomes. This study investigates the efficacy of folate and vitamin B6 supplementation as an adjunct to sodium valproate in improving treatment responses for patients experiencing acute mania.
In a randomized, double-blind, placebo-controlled trial, 43 patients diagnosed with bipolar I disorder presenting with acute manic episodes were enrolled. Participants were randomly assigned to three groups: one receiving folate (5 mg/day) plus vitamin B6 (80 mg/day), a second group receiving folate alone (5 mg/day), and a third group receiving placebo. Evaluations were conducted at baseline and after 3 and 6 weeks using the Mini-Mental State Examination (MMSE) and the Young Mania Rating Scale (YMRS).
All groups demonstrated significant clinical improvements after the treatment period; however, the trends in MMSE scores showed no significant differences (p = 0.068). Notably, the reduction in YMRS scores significantly varied across groups (p < 0.001, effect size = 0.342), with the folate group demonstrating a significantly greater decrease compared to both the folate/B6 (p = 0.003) and placebo groups (p < 0.001). Recovery rates revealed that 80% of patients receiving folate showed over a 50% decrease in YMRS scores after 3 weeks, markedly higher than the other groups (p = 0.001).
Our findings support the short-term use of folate as a beneficial adjunct in treating acute manic episodes in bipolar I disorder. However, the addition of vitamin B6 did not yield additional advantages. These results may inform future treatment guidelines targeting acute mania in bipolar disorder, advocating for folate supplementation as a potential strategy to enhance therapeutic outcomes.
耐药性在双相 I 型障碍急性躁狂发作的治疗中构成了巨大挑战，导致治疗效果欠佳。本研究调查了补充叶酸和维生素 B6 作为丙戊酸钠辅助治疗手段，对急性躁狂发作患者治疗反应的改善效果。
在一项随机、双盲、安慰剂对照试验中，纳入了 43 例诊断为双相 I 型障碍且伴有急性躁狂发作的患者。参与者被随机分为三组：一组接受叶酸（5 毫克/天）加维生素 B6（80 毫克/天），第二组仅接受叶酸（5 毫克/天），第三组接受安慰剂。在基线以及 3 周和 6 周后，使用简易精神状态检查表（MMSE）和青年躁狂评定量表（YMRS）进行评估。
治疗期后所有组均显示出显著的临床改善；然而，MMSE 评分趋势无显著差异（p = 0.068）。值得注意的是，YMRS 评分的降低在各组间差异显著（p < 0.001，效应大小 = 0.342），叶酸组相较于叶酸/B6 组（p = 0.003）和安慰剂组（p < 0.001），YMRS 评分降低幅度显著更大。恢复率显示，接受叶酸治疗的患者中，80%在 3 周后 YMRS 评分下降超过 50%，明显高于其他组（p = 0.001）。
我们的研究结果支持短期使用叶酸作为治疗双相 I 型障碍急性躁狂发作的有益辅助手段。然而，添加维生素 B6 并未带来额外益处。这些结果可能为未来双相情感障碍急性躁狂发作的治疗指南提供参考，提倡补充叶酸作为提高治疗效果的潜在策略。
