Pierre Joseph M
David Geffen School of Medicine at UCLA, VA Greater Los Angeles Healthcare System, Los Angeles, California, USA.
Drug Saf. 2005;28(3):191-208. doi: 10.2165/00002018-200528030-00002.
The treatment of schizophrenia changed drastically with the discovery of antipsychotic medications in the 1950s, the release of clozapine in the US in 1989 and the subsequent development of the atypical or novel antipsychotics. These newer medications differ from their conventional counterparts, primarily based on their reduced risk of extrapyramidal symptoms (EPS). EPS can be categorised as acute (dystonia, akathisia and parkinsonism) and tardive (tardive dyskinesia and tardive dystonia) syndromes. They are thought to have a significant impact on subjective tolerability and adherence with antipsychotic therapy in addition to impacting function. Unlike conventional antipsychotic medications, atypical antipsychotics have a significantly diminished risk of inducing acute EPS at recommended dose ranges. These drugs may also have a reduced risk of causing tardive dyskinesia and in some cases may have the ability to suppress pre-existing tardive dyskinesia. This paper reviews the available evidence regarding the incidence of acute EPS and tardive syndromes with atypical antipsychotic therapy. Estimates of incidence are subject to several confounds, including differing methods for detection and diagnosis of EPS, pretreatment effects and issues surrounding the administration of antipsychotic medications. The treatment of acute EPS and tardive dyskinesia now includes atypical antipsychotic therapy itself, although other adjunctive strategies such as antioxidants have also shown promise in preliminary trials. The use of atypical antipsychotics as first line therapy for the treatment of schizophrenia is based largely on their reduced risk of EPS compared with conventional antipsychotics. Nevertheless, EPS with these drugs can occur, particularly when prescribed at high doses. The EPS advantages offered by the atypical antipsychotics must be balanced against other important adverse effects, such as weight gain and diabetes mellitus, now known to be associated with these drugs.
20世纪50年代抗精神病药物的发现、1989年氯氮平在美国的上市以及随后非典型或新型抗精神病药物的研发,使精神分裂症的治疗发生了巨大变化。这些新型药物与传统药物不同,主要在于它们引发锥体外系症状(EPS)的风险较低。EPS可分为急性(肌张力障碍、静坐不能和帕金森症)和迟发性(迟发性运动障碍和迟发性肌张力障碍)综合征。除影响功能外,它们还被认为对主观耐受性和抗精神病治疗的依从性有重大影响。与传统抗精神病药物不同,非典型抗精神病药物在推荐剂量范围内引发急性EPS的风险显著降低。这些药物引发迟发性运动障碍的风险也可能降低,在某些情况下可能有能力抑制已有的迟发性运动障碍。本文综述了关于非典型抗精神病药物治疗急性EPS和迟发性综合征发生率的现有证据。发生率的估计受到多种混杂因素的影响,包括EPS检测和诊断方法的不同、预处理效应以及抗精神病药物给药相关问题。急性EPS和迟发性运动障碍的治疗现在包括非典型抗精神病药物治疗本身,尽管其他辅助策略如抗氧化剂在初步试验中也显示出前景。非典型抗精神病药物作为精神分裂症一线治疗药物的使用,很大程度上是基于与传统抗精神病药物相比,它们引发EPS的风险较低。然而,这些药物仍可能引发EPS,尤其是高剂量处方时。非典型抗精神病药物的EPS优势必须与其他重要不良反应相权衡,如体重增加和糖尿病,现在已知这些药物与这些不良反应有关。