Murray Robin, Correll Christoph U, Reynolds Gavin P, Taylor David
Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, UK.
Hofstra Northwell School of Medicine, The Zucker Hillside Hospital, New York, USA.
Ther Adv Psychopharmacol. 2017 Mar;7(1 Suppl):1-14. doi: 10.1177/2045125317693200. Epub 2017 Mar 1.
Available evidence suggests that second-generation atypical antipsychotics are broadly similar to first-generation agents in terms of their efficacy, but may have a more favourable tolerability profile, primarily by being less likely to cause extrapyramidal symptoms. However, atypical antipsychotics are variably associated with disturbances in the cardiometabolic arena, including increased body weight and the development of metabolic syndrome, which may reflect differences in their receptor binding profiles. Effective management of schizophrenia must ensure that the physical health of patients is addressed together with their mental health. This should therefore involve consideration of the specific tolerability profiles of available agents and individualization of treatment to minimize the likelihood of adverse metabolic sequelae, thereby improving long-term adherence and optimizing overall treatment outcomes. Alongside this, modifiable risk factors (such as exercise, diet, obesity/body weight and smoking status) must be addressed, in order to optimize patients' overall health and quality of life (QoL). In addition to antipsychotic-induced side effects, the clinical management of early nonresponders and psychopharmacological approaches for patients with treatment-resistant schizophrenia remain important unmet needs. Evidence suggests that antipsychotic response starts early in the course of treatment and that early nonresponse accurately predicts nonresponse over the longer term. Early nonresponse therefore represents an important modifiable risk factor for poor efficacy and effectiveness outcomes, since switching or augmenting antipsychotic treatment in patients showing early nonresponse has been shown to improve the likelihood of subsequent treatment outcomes. Recent evidence has also demonstrated that patients showing early nonresponse to treatment with lurasidone at 2 weeks may benefit from an increase in dose at this timepoint without compromising tolerability/safety. However, further research is required to determine whether these findings are generalizable to other antipsychotic agents.
现有证据表明,第二代非典型抗精神病药物在疗效方面与第一代药物大致相似,但耐受性可能更好,主要是因为引发锥体外系症状的可能性较小。然而,非典型抗精神病药物与心脏代谢领域的紊乱存在不同程度的关联,包括体重增加和代谢综合征的发生,这可能反映了它们受体结合谱的差异。精神分裂症的有效管理必须确保在关注患者心理健康的同时,也关注其身体健康。因此,这应涉及考虑现有药物的具体耐受性特征,并实现治疗个体化,以尽量降低不良代谢后遗症的可能性,从而提高长期依从性并优化总体治疗效果。与此同时,必须解决可改变的风险因素(如运动、饮食、肥胖/体重和吸烟状况),以优化患者的整体健康和生活质量(QoL)。除了抗精神病药物引起的副作用外,早期无反应者的临床管理以及难治性精神分裂症患者的精神药理学方法仍然是尚未满足的重要需求。有证据表明,抗精神病药物的反应在治疗过程早期就开始出现,早期无反应准确预测了长期无反应。因此,早期无反应是疗效不佳和治疗效果差的一个重要可改变风险因素,因为在早期无反应的患者中更换或增加抗精神病药物治疗已被证明可提高后续治疗效果的可能性。最近的证据还表明,在2周时对鲁拉西酮治疗早期无反应的患者,此时增加剂量可能有益,且不会影响耐受性/安全性。然而,需要进一步研究以确定这些发现是否可推广到其他抗精神病药物。