Goldberg Joseph F, Steinman Michael Q, Stahl Stephen M
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Arbor Scientia Group, 5962 La Place Court, Suite 290, Carlsbad, CA, 92008, USA.
Neurosci Appl. 2023 May 22;2:101127. doi: 10.1016/j.nsa.2023.101127. eCollection 2023.
Psychotropic drug properties can vary across different formulations of a compound. Trazodone is a multifunctional drug that exemplifies this phenomenon. Although it is a serotonin reuptake inhibitor, trazodone is a significantly more potent blocker of serotonin 5-HT2A receptors. It also acts as an antagonist at several other 5-HT receptors and acts as a partial agonist at 5-HT1A receptors. Additional targets of trazodone blockade include histamine H1 receptors and alpha-1 adrenergic receptors. Trazodone's newer once-a-day (OAD) formulation is thought to have improved safety and tolerability over earlier formulations due to release kinetics that avoid the multiple higher peaks in plasma concentrations observed with earlier formulations. Here, we systematically reviewed the clinical data from randomized controlled trials (RCTs). We performed a PubMed and Cochrane Library database search for RCTs on trazodone OAD that either included placebo or active comparator controls or used a crossover design with at least one additional treatment. Three studies met inclusion criteria. Trazodone OAD was compared to placebo in one study, to venlafaxine extended-release (XR) in another, and to trazodone immediate-release in an additional study. Trazodone OAD demonstrated a favorable safety and tolerability profile across studies and was associated with low levels of sexual dysfunction and weight gain. It improved sleep disturbance scores and was associated with time point-dependent improvements in anxiety/somatization scores on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) as compared to placebo or venlafaxine XR, suggesting that it does not tend to promote anxiety or insomnia. Trazodone OAD represents a well-tolerated treatment for MDD patients who are concerned by anxiety symptoms and are seeking to minimize adverse drug effects involving sexual dysfunction, weight gain, and psychomotor activation.
精神药物的特性在化合物的不同制剂中可能会有所不同。曲唑酮就是一种体现这种现象的多功能药物。虽然它是一种5-羟色胺再摄取抑制剂，但曲唑酮是一种效力显著更强的5-羟色胺5-HT2A受体阻滞剂。它还作为其他几种5-HT受体的拮抗剂，并作为5-HT1A受体的部分激动剂发挥作用。曲唑酮阻断的其他靶点包括组胺H1受体和α-1肾上腺素能受体。曲唑酮较新的每日一次（OAD）制剂被认为比早期制剂具有更好的安全性和耐受性，这归因于其释放动力学，可避免早期制剂中观察到的血浆浓度多次出现更高峰值。在此，我们系统回顾了来自随机对照试验（RCT）的临床数据。我们在PubMed和Cochrane图书馆数据库中搜索关于曲唑酮OAD的RCT，这些试验要么包括安慰剂或活性对照，要么采用至少一种额外治疗的交叉设计。三项研究符合纳入标准。在一项研究中，将曲唑酮OAD与安慰剂进行比较，在另一项研究中与文拉法辛缓释剂（XR）进行比较，在另一项研究中与曲唑酮速释剂进行比较。在各项研究中，曲唑酮OAD均显示出良好的安全性和耐受性，且与性功能障碍和体重增加水平较低相关。与安慰剂或文拉法辛XR相比，它改善了睡眠障碍评分，并与17项汉密尔顿抑郁量表（HAM-D-17）上焦虑/躯体化评分的时间点依赖性改善相关，这表明它不太容易引发焦虑或失眠。对于担心焦虑症状并寻求尽量减少涉及性功能障碍、体重增加和精神运动激活的药物不良反应的重度抑郁症（MDD）患者，曲唑酮OAD是一种耐受性良好的治疗方法。
