Orosomucoid influences the response to antidepressants in major depressive disorder
Orosomucoid influences the response to antidepressants in major depressive disorder
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DOI：
10.1177/0269881109105101
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发表时间：
2010-04-01
影响因子：
4.1
通讯作者：
Kennedy, M.
中科院分区：
文献类型：
--
作者：
Harley, J.;Roberts, R.;Kennedy, M.
Orosomucoid是一种急性期蛋白，在血浆中携带包括抗抑郁药在内的基本药物。据报道，抑郁症患者的水平升高。目前尚未确定类粘蛋白浓度是否影响抗抑郁反应。orosomucoid基因（ORM 1）具有多态性，其蛋白质异构体具有不同的药代动力学特性，可改变抗抑郁药的血浆分布和血脑屏障转运。在氟西汀与去甲替林的随机对照试验中，对门诊患者（n = 157）进行ORM 1变异体基因分型。还测量了急性时相蛋白的血浆浓度。结果是完成了为期6周的抗抑郁药和反应的充分试验。反应定义为在6周内蒙哥马利抑郁量表（MADRS）改善≥ 60%。第一个值得注意的发现是，具有ORM 1 *S/*S基因型的个体不太可能完成足够的6周抗抑郁药试验（OR = 4.707，95%CI 1.769-12.527，P = 0.002）。抗抑郁药无应答者血清类粘蛋白浓度（91.4%）高于应答者（79.1%）（F1，106 = 5.669，P = 0.019）。这些发现突出了诸如类粘蛋白等变量的潜在重要性，这些变量影响抗抑郁药物的治疗效果的药物可用性。
Orosomucoid, an acute phase protein, carries basic drugs including antidepressants in plasma. Elevated levels have been reported in patients with depression. It has yet to be established whether orosomucoid concentration influences antidepressant response. The orosomucoid gene (ORM1) is polymorphic and the protein isoforms have differing pharmacokinetic properties which could alter plasma profile and blood brain barrier transport of antidepressants. Outpatients (n = 157) in a randomised control trial of fluoxetine versus nortriptyline were genotyped for the ORM1 variants. Plasma concentrations of acute phase proteins were also measured. Outcomes were the completion of an adequate six week trial of antidepressant and response. Response was defined as an improvement >= 60% on the Montgomery-Asperg Depression Rating Scale (MADRS) over six weeks. The first notable finding was that individuals with an ORM1*S/*S genotype were less likely to complete an adequate six week trial of an antidepressant (OR = 4.707, 95% CI 1.769-12.527, P = 0.002). The second was that higher orosomucoid concentrations were found in antidepressant non-responders (91.4%) than responders (79.1%) (F1, 106 = 5.669, P = 0.019). These findings highlight the potential importance of variables such as orosomucoid which impact on drug availability on the therapeutic efficacy of antidepressant drugs.