Effects of early clozapine treatment on remission rates in acute schizophrenia (EARLY)

在精神病性症状发作后迅速实现症状缓解是精神分裂症治疗的关键目标，并决定了随后的病程。在这种情况下，只有第二个急性精神分裂症患者在开始抗精神病药物治疗的三个月内达到症状缓解，这意味着一半的患者没有达到这一关键目标。增加急性精神分裂症症状缓解的可能性将改善总体结局，减少疾病相关负担，并可能预防中长期疾病慢性化。通过这项随机、双盲、平行组、多中心试验，我们旨在提供证据，证明“最后手段”抗精神病药氯氮平在不符合初治或难治性精神分裂症标准的急性精神分裂症患者中的上级疗效优于最有效的第二代抗精神病药（SGA）之一奥氮平。我们的目标人群代表了最大的精神分裂症患者群体;这些患者经常住院，并接受德国所有精神病住院治疗的约20%。来自8个学术中心的共220例急性精神分裂症患者将随机接受氯氮平或奥氮平双盲、8周治疗。主要终点是根据国际共识标准（“Andreasen标准”）在第8周结束时症状缓解的患者数量。次要终点包括例如症状严重程度、疾病严重程度、整体功能、认知、副作用维度以及患者和亲属对治疗的看法。

Achieving symptomatic remission quickly after the onset of psychotic symptoms is the critical objective in schizophrenia treatment and determines the subsequent disease course. In this context, only every second patient with acute schizophrenia achieves symptomatic remission within three months of initiating antipsychotic treatment, meaning that half of patients do not achieve this key objective. Increasing the likelihood to achieve symptomatic remission in acute schizophrenia will improve the overall outcome, reduce disease-associated burden and potentially prevent mid- and long-term disease chronicity. With this randomized, double-blind, parallel-group multicentre trial we aim to provide evidence for the superior efficacy of the ‘last resort’ antipsychotic clozapine compared to one of the most effective second-generation antipsychotics (SGAs), olanzapine, in acute schizophrenia patients who do not meet the criteria for treatment-naive or treatment-resistant schizophrenia. Our target population represents the largest group of schizophrenia patients; these patients are frequently hospitalized and receive ~20% of all psychiatric inpatient treatments in Germany. A total of 220 patients from eight academic centres with acute schizophrenia will be randomized to a double-blind, eight-week treatment with either clozapine or olanzapine. The primary endpoint is the number of patients in symptomatic remission at the end of week eight according to the international consensus criteria (‘Andreasen criteria’). Secondary endpoints include e.g. symptom severity, disease severity, global functioning, cognition, side-effect dimensions and patients’ and relatives’ view on treatment.