Seeman Mary V
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Front Psychiatry. 2021 Apr 9;12:650904. doi: 10.3389/fpsyt.2021.650904. eCollection 2021.
Animal and human experiments have confirmed sex differences in the expression of hepatic enzymes that metabolize antipsychotic drugs and that may, in this way, be partly responsible for the clinical sex/gender differences observed in the efficacy and tolerability of antipsychotic treatment. The aim of this mini review is to synthesize the literature on the pharmacodynamics of male/female differential response to antipsychotic drugs. Relevant search terms were used to search for pre-clinical and human trials and analysis of antipsychotic differential drug response and occurrence/severity of adverse effects in women and men. The search found that sex influences drug response the amount of a given drug that enters the brain and the number of neurotransmitter receptors to which it can bind. Consequently, sex partly determines the efficacy of a specific drug and its liability to induce unwanted effects. There are other factors that can overshadow or enhance the dimorphic effect of sex, for instance, the host's age, hormonal status, diet and life style as well as the molecular structure of the drug and its dose, and the method of its administration. Most of all, the host's individual genetics affects each step of a drug's pharmacodynamics. On average, women's psychotic symptoms respond to antipsychotic drugs at doses lower than men's. This means that many women may be overdosed and, thus, experience unnecessary adverse effects. That being said, factors such as genetics and age probably determine drug response and tolerability to a greater degree than do biological sex or gender social roles.
动物实验和人体实验均已证实,在代谢抗精神病药物的肝脏酶表达方面存在性别差异,而这可能在一定程度上导致了抗精神病治疗在疗效和耐受性方面出现临床性别差异。本综述的目的是综合有关抗精神病药物男女差异反应药效学的文献。使用相关检索词搜索了临床前研究和人体试验,以及关于抗精神病药物差异反应和男女不良反应发生情况/严重程度的分析。研究发现,性别会影响药物反应,即进入大脑的特定药物的量以及它能够结合的神经递质受体的数量。因此,性别在一定程度上决定了特定药物的疗效及其产生不良影响的可能性。还有其他一些因素可能会掩盖或增强性别的双态效应,例如宿主的年龄、激素状态、饮食和生活方式,以及药物的分子结构、剂量及其给药方法。最重要的是,宿主的个体基因会影响药物药效学的每一个环节。平均而言,女性的精神病症状对抗精神病药物的反应剂量低于男性。这意味着许多女性可能用药过量,从而出现不必要的不良反应。话虽如此,与生理性别或性别社会角色相比,基因和年龄等因素可能在更大程度上决定药物反应和耐受性。