Yale School of Medicine, New Haven, Connecticut, USA.
Br J Psychiatry. 2012 May;200(5):387-92. doi: 10.1192/bjp.bp.111.101485. Epub 2012 Mar 22.
Second-generation antipsychotics have been thought to cause fewer extrapyramidal side-effects (EPS) than first-generation antipsychotics, but recent pragmatic trials have indicated equivalence.
To determine whether second-generation antipsychotics had better outcomes in terms of EPS than first-generation drugs.
We conducted an intention-to-treat, secondary analysis of data from an earlier randomised controlled trial (n = 227). A clinically significant difference was defined as double or half the symptoms in groups prescribed first- v. second-generation antipsychotics, represented by odds ratios greater than 2.0 (indicating advantage for first-generation drugs) or less than 0.5 (indicating advantage for the newer drugs). We also examined EPS in terms of symptoms emergent at 12 weeks and 52 weeks, and symptoms that had resolved at these time points.
At baseline those randomised to the first-generation antipsychotic group (n = 118) had similar EPS to the second-generation group (n = 109). Indications of resolved Parkinsonism (OR = 0.5) and akathisia (OR = 0.4) and increased tardive dyskinesia (OR = 2.2) in the second-generation drug group at 12 weeks were not statistically significant and the effects were not present by 52 weeks. Patients in the second-generation group were dramatically (30-fold) less likely to be prescribed adjunctive anticholinergic medication, despite equivalence in terms of EPS.
The expected improvement in EPS profiles for participants randomised to second-generation drugs was not found; the prognosis over 1 year of those in the first-generation arm was no worse in these terms. The place of careful prescription of first-generation drugs in contemporary practice remains to be defined, potentially improving clinical effectiveness and avoiding life-shortening metabolic disturbances in some patients currently treated with the narrow range of second-generation antipsychotics used in routine practice. This has educational implications because a generation of psychiatrists now has little or no experience with first-generation antipsychotic prescription.
第二代抗精神病药被认为比第一代抗精神病药引起的锥体外系副作用（EPS）更少，但最近的实用临床试验表明两者相当。
确定第二代抗精神病药在 EPS 方面是否优于第一代药物。
我们对先前一项随机对照试验（n = 227）的数据进行了意向治疗、二次分析。具有临床意义的差异定义为在服用第一代或第二代抗精神病药的组中，症状翻倍或减半，用比值比大于 2.0（表示第一代药物有利）或小于 0.5（表示新药有利）表示。我们还检查了 12 周和 52 周时出现的 EPS 症状以及这些时间点已解决的症状。
在基线时，随机分配到第一代抗精神病药组（n = 118）的患者与第二代组（n = 109）的 EPS 相似。第二代药物组在 12 周时出现的帕金森病缓解（OR = 0.5）、静坐不能缓解（OR = 0.4）和迟发性运动障碍增加（OR = 2.2）的迹象并不具有统计学意义，并且在 52 周时这些效应不再存在。尽管在 EPS 方面等效，但第二代药物组的患者接受辅助抗胆碱能药物治疗的可能性低 30 倍。
没有发现随机分配到第二代药物的患者 EPS 谱预期改善；在这些方面，第一代药物组的患者在 1 年内的预后并没有更差。需要谨慎处方第一代药物，这在当代实践中仍有待确定，这可能会提高临床疗效，并避免目前使用常规实践中狭窄范围的第二代抗精神病药治疗的一些患者出现缩短寿命的代谢紊乱。这具有教育意义，因为现在一代精神科医生对第一代抗精神病药的处方经验很少或没有。
