Pae Chi-Un, Lim Hyun-Kook, Han Changsu, Neena Ajwani, Lee Chul, Patkar Ashwin A
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2007 Aug 15;31(6):1153-63. doi: 10.1016/j.pnpbp.2007.04.020. Epub 2007 May 10.
Many monoamine oxidase inhibitors (MAOIs) have been used to treat major depressive disorder (MDD). However, the prescription of MAOIs has decreased considerably as a result of side effects such as tyramine-induced hypertensive crisis, which is also known as the 'Cheese Effect'. The drug delivery system itself can affect the bioavailability of certain drugs, which might influence the efficacy and tolerability of medications, as well as improve the compliance and reduce the incidence of recurrence and relapse. Therefore, there is a need for advanced drug delivery techniques that can evade the potentially hazardous toxic effects of the parent compound, including extended-release oral, cutaneous, intravesical and intravaginal routes, etc. In this context, the selegiline transdermal system (STS, EMSAM) was introduced with improved side effect profiles and efficacy compared with the conventional form of the selegiline oral tablet. STS allows the targeted inhibition of the monoamine A (MAO-A) and MAO-B isoenzymes with minimal effects on the MAO-A in the gastrointestinal and hepatic systems. Hence, STS can reduce the risk of interactions with tyramine-rich foods. Many fundamental clinical and preclinical studies have reported that 6 mg/24 h of STS is effective against MDD without the need for dietary restrictions with an equal efficacy and improved safety profile. In addition, STS might benefit MDD patients with atypical features or who are resistant to other antidepressants. Overall, familiarity with the properties and indications of STS will have the clinicians another option of biological treatments for MDD patients but subsequent more data including actual post-market clinical experiences will be mandatory.
许多单胺氧化酶抑制剂(MAOIs)已被用于治疗重度抑郁症(MDD)。然而,由于诸如酪胺诱发的高血压危象等副作用,MAOIs的处方量已大幅下降,这种副作用也被称为“奶酪效应”。药物递送系统本身会影响某些药物的生物利用度,这可能会影响药物的疗效和耐受性,以及提高依从性并降低复发率。因此,需要先进的药物递送技术,以规避母体化合物潜在的有害毒性作用,包括缓释口服、经皮、膀胱内和阴道内给药途径等。在此背景下,与传统的司来吉兰口服片剂相比,司来吉兰透皮系统(STS,EMSAM)具有改善的副作用特征和疗效。STS能够靶向抑制单胺氧化酶A(MAO-A)和MAO-B同工酶,同时对胃肠道和肝脏系统中的MAO-A影响最小。因此,STS可以降低与富含酪胺食物相互作用的风险。许多基础临床和临床前研究报告称,24小时6毫克的STS对MDD有效,无需饮食限制,疗效相当且安全性更高。此外,STS可能对具有非典型特征或对其他抗抑郁药耐药的MDD患者有益。总体而言,熟悉STS的特性和适应症将为临床医生提供另一种治疗MDD患者的生物疗法选择,但后续需要更多数据,包括实际的上市后临床经验。