Coppen A, Bailey J
MRC Neuropsychiatry Laboratory, West Park Hospital, KT19 8PB, Surrey, Epsom, UK.
J Affect Disord. 2000 Nov;60(2):121-30. doi: 10.1016/s0165-0327(00)00153-1.
A consistent finding in major depression has been a low plasma and red cell folate which has also been linked to poor response to antidepressants. The present investigation was designed to investigate whether the co-administration of folic acid would enhance the antidepressant action of fluoxetine.
127 patients were randomly assigned to receive either 500 microg folic acid or an identical looking placebo in addition to 20 mg fluoxetine daily. All patients met the DSM-III-R criteria for major depression and had a baseline Hamilton Rating Scale (17 item version) score for depression of 20 or more. Baseline and 10-week estimations of plasma folate and homocysteine were carried out.
Patients receiving folate showed a significant increase in plasma folate. This was less in men than in women. Plasma homocysteine was significantly decreased in women by 20.6%, but there was no significant change in men. Overall there was a significantly greater improvement in the fluoxetine plus folic acid group. This was confined to women where the mean Hamilton Rating Scale score on completion was 6.8 (S.D. 4. 1) in the fluoxetine plus folate group, as compared to 11.7 (S.D. 6. 7) in the fluoxetine plus placebo group (P<0.001).A percentage of 93. 9 of women, who received the folic acid supplement, showed a good response (>50% reduction in score) as compared to 61.1% of women who received placebo supplement (P<0.005). Eight (12.9%) patients in the fluoxetine plus folic acid group reported symptoms possibly or probably related to medication, whereas in the fluoxetine plus placebo group 19 (29.7%) patients reported such symptoms (P<0.05).
Folic acid is a simple method of greatly improving the antidepressant action of fluoxetine and probably other antidepressants. Folic acid should be given in doses sufficient to decrease plasma homocysteine. Men require a higher dose of folic acid to achieve this than women, but more work is required to ascertain the optimum dose of folic acid.
重度抑郁症患者中一个一致的发现是血浆和红细胞叶酸水平较低，这也与对抗抑郁药反应不佳有关。本研究旨在调查叶酸联合使用是否会增强氟西汀的抗抑郁作用。
127名患者被随机分配，除每日服用20mg氟西汀外，分别接受500微克叶酸或外观相同的安慰剂。所有患者均符合DSM-III-R重度抑郁症标准，且汉密尔顿抑郁量表（17项版本）基线抑郁评分达20分或更高。进行了血浆叶酸和同型半胱氨酸的基线及10周评估。
接受叶酸治疗的患者血浆叶酸显著增加。男性增加幅度小于女性。女性血浆同型半胱氨酸显著降低20.6%，但男性无显著变化。总体而言，氟西汀加叶酸组改善更为显著。这仅限于女性，氟西汀加叶酸组完成时汉密尔顿抑郁量表平均评分6.8（标准差4.1），而氟西汀加安慰剂组为11.7（标准差6.7）（P<0.001）。接受叶酸补充剂的女性中有93.9%显示出良好反应（评分降低>50%），而接受安慰剂补充剂的女性为61.1%（P<0.005）。氟西汀加叶酸组有8名（12.9%）患者报告了可能或很可能与药物相关的症状，而氟西汀加安慰剂组有19名（29.7%）患者报告了此类症状（P<0.05）。
叶酸是一种能显著增强氟西汀及可能其他抗抑郁药抗抑郁作用的简单方法。应给予足够剂量的叶酸以降低血浆同型半胱氨酸。男性达到此目的所需的叶酸剂量高于女性，但还需要更多研究来确定叶酸的最佳剂量。
