Kane John M, Correll Christoph U
Zucker Hillside Hospital, 75-59 263rd Street, Glen Oaks, NY 11004, USA.
Dialogues Clin Neurosci. 2010;12(3):345-57. doi: 10.31887/DCNS.2010.12.3/jkane.
Despite pharmacologic advances, the treatment of schizophrenia remains a challenge, and suboptimal outcomes are still all too frequent. Although treatment goals of response, remission, and recovery have been defined more uniformly, a good "effectiveness" measure mapping onto functional outcomes is still lacking. Moreover, the field has to advance in transferring measurement-based approaches from research to clinical practice. There is an ongoing debate whether, and which, first- or second-generation antipsychotics should be used. However an individualized treatment approach needs to consider current symptoms, comorbid conditions, past therapeutic response, and adverse effects, as well as patient choice and expectations. Moreover acute and long-term goals and effects of medication treatment need to be balanced. While the acute response to appropriately dosed first-generation antipsychotics may not differ much from second-generation antipsychotics, advantages of lower rates of extrapyramidal side effects, tardive dyskinesia, and, possibly, relapse may favor second-generation antipsychotics. However when considering individual adverse effect profiles, the differentiation into first- and second-generation antipsychotics as unified classes can not be upheld, and a more differentiated view and treatment selection is required. To date, clozapine is the only evidence-based treatment for refractory patients, and the role of antipsychotic polypharmacy and other augmentation strategies remains unclear, at best. To improve the treatment outcomes in schizophrenia, research efforts are needed that elucidate biomarkers of the illness and of treatment response (both therapeutic and adverse effects). Moreover, new treatment options are needed that affect nondopaminergic targets with relevance for symptom reduction, relapse prevention, enhanced efficacy for nonresponders, and reduced key adverse effects.
尽管药理学取得了进展,但精神分裂症的治疗仍然是一项挑战,治疗效果欠佳的情况仍然屡见不鲜。虽然反应、缓解和康复等治疗目标的定义更加统一,但仍缺乏一种能映射到功能结局的良好“有效性”测量方法。此外,该领域在将基于测量的方法从研究转化到临床实践方面仍需取得进展。关于是否应使用以及应使用哪种第一代或第二代抗精神病药物,目前仍存在争议。然而,个体化治疗方法需要考虑当前症状、共病情况、既往治疗反应和不良反应,以及患者的选择和期望。此外,药物治疗的短期和长期目标及效果需要平衡。虽然适当剂量的第一代抗精神病药物的急性反应可能与第二代抗精神病药物没有太大差异,但锥体外系副作用、迟发性运动障碍发生率较低以及可能较低的复发率等优势可能有利于第二代抗精神病药物。然而,考虑到个体不良反应特征时,将第一代和第二代抗精神病药物作为统一类别进行区分是站不住脚的,需要更具差异化的观点和治疗选择。迄今为止,氯氮平是唯一一种针对难治性患者的循证治疗药物,而抗精神病药物联合治疗及其他增效策略的作用充其量仍不明确。为了改善精神分裂症的治疗效果,需要开展研究工作来阐明该疾病及治疗反应(包括治疗效果和不良反应)的生物标志物。此外,还需要新的治疗选择,这些选择能够作用于与症状减轻、预防复发、提高无反应者疗效以及减少关键不良反应相关的非多巴胺能靶点。