Molden Espen, Spigset Olav
Farmasøytisk institutt, Universitetet i Oslo, Norway.
Tidsskr Nor Laegeforen. 2011 Sep 20;131(18):1777-9. doi: 10.4045/tidsskr.11.0143.
Metoprolol, the most commonly used beta-receptor antagonist in Norway, is eliminated mainly via the enzyme cytochrome P450 (CYP) 2D6. This enzyme is inhibited to a varying extent by antidepressants. The aim of this article is to provide an overview of the interactions between metoprolol and antidepressants with an emphasis on CYP2D6 inhibition.
Relevant literature was identified by a PubMed search using the word "metoprolol" combined with generic names of antidepressant drugs.
The potent CYP2D6 inhibitor paroxetine has been shown to increase the biologically available dose of metoprolol about 4- to 6-fold. The same degree of increase is expected for the two other potent CYP2D6 inhibitors in the class, fluoxetine and bupropion. Severe bradycardia and atroventricular block has been reported in patients who have taken metoprolol in combination with these three drugs. Escitalopram, citalopram and duloxetine are less potent CYP2D6 inhibitors, and have been shown to cause 2- to 3-fold increases in biologically available dose of metoprolol. Other antidepressants, such as sertraline, venlafaxine, mianserin and mirtazapine, inhibit CYP2D6 to little or no extent, and are not expected to cause clinically relevant interactions with metoprolol.
Metoprolol should not be used concomitantly with paroxetine, fluoxetine or bupropion due to extensive interactions and the risk of serious adverse effects. Dose reductions of metoprolol should be considered for combined treatment with citalopram, escitalopram or duloxetine, while concurrent use with sertraline, venlafaxine, mianserin and mirtazapine should be safe.
美托洛尔是挪威最常用的β受体拮抗剂，主要通过细胞色素P450（CYP）2D6酶代谢。这种酶会受到抗抑郁药不同程度的抑制。本文旨在概述美托洛尔与抗抑郁药之间的相互作用，重点是CYP2D6抑制作用。
通过PubMed检索，使用“美托洛尔”一词与抗抑郁药通用名相结合来识别相关文献。
强效CYP2D6抑制剂帕罗西汀已被证明可使美托洛尔的生物利用剂量增加约4至6倍。该类中的另外两种强效CYP2D6抑制剂氟西汀和安非他酮预计也会有相同程度的增加。据报道，服用美托洛尔与这三种药物联合使用的患者出现了严重心动过缓和房室传导阻滞。艾司西酞普兰、西酞普兰和度洛西汀是较弱的CYP2D6抑制剂，已被证明可使美托洛尔的生物利用剂量增加2至3倍。其他抗抑郁药，如舍曲林、文拉法辛、米安色林和米氮平，对CYP2D6的抑制作用很小或没有，预计不会与美托洛尔产生临床相关的相互作用。
由于广泛的相互作用和严重不良反应的风险，美托洛尔不应与帕罗西汀、氟西汀或安非他酮同时使用。与西酞普兰、艾司西酞普兰或度洛西汀联合治疗时，应考虑减少美托洛尔的剂量，而与舍曲林、文拉法辛、米安色林和米氮平同时使用应该是安全的。
