Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Transl Psychiatry. 2023 Jun 7;13(1):191. doi: 10.1038/s41398-023-02491-6.
Greater initial severity on the 30-item Positive and Negative Syndrome Scale (PANSS-30) correlates positively with antipsychotic-placebo separation and trial dropout, but it is unknown whether these associations are present also on PANSS-derived subscales. We assessed the relationship between initial severity and antipsychotic-placebo separation as measured by PANSS-30 and four PANSS symptom subscales: the positive (PANSS-POS), negative (PANSS-NEG), general (PANSS-GEN) and 6-item (PANSS-6) subscales, using patient-level data from 18 placebo-controlled risperidone and paliperidone trials. Analysis of covariance in the intention-to-treat population (last-observation-carried-forward) was used to assess antipsychotic-placebo separation and trial dropout. Across 6685 participants (90% schizophrenia, 10% schizoaffective disorder), the initial severity-by-treatment interaction was statistically significant for PANSS-30 (beta: -0.155; p < 0.001) and all PANSS subscales (beta range: -0.097 to -0.135; p-value range: < 0.001 to 0.002). In all cases, antipsychotic-placebo differences increased with initial severity. Judging by the distribution of relative outcomes (percent remaining symptoms), the interaction was partly explained by an increased chance of responding, but also by larger numerical responses in those who did respond, as initial severity increased. Except for PANSS-NEG, high initial severity on all PANSS scales predicted increased trial dropout, although not statistically significantly so for PANSS-6. In summary, we thus replicate previous findings showing greater initial severity to predict larger antipsychotic-placebo separation and extend these results to four PANSS subscales. For PANSS-POS and PANSS-GEN, but not for PANSS-NEG and PANSS-6, we also replicate the association between initial severity and trial dropout. Patients with low initial negative symptom severity were identified as a group of particular interest for further study since their results diverged most from the average both with regard to antipsychotic-placebo separation (low separation measured by PANSS-NEG) and trial dropout (high level).
在 30 项阳性和阴性症状量表（PANSS-30）上，初始严重程度越高，与抗精神病药和安慰剂的分离以及试验脱落呈正相关，但尚不清楚这些关联是否也存在于 PANSS 衍生的子量表上。我们评估了初始严重程度与 PANSS-30 和四个 PANSS 症状子量表（阳性 PANSS-POS、阴性 PANSS-NEG、一般 PANSS-GEN 和 6 项 PANSS-6）测量的抗精神病药和安慰剂分离之间的关系，使用了来自 18 项利培酮和帕利哌酮安慰剂对照试验的患者水平数据。采用意向治疗人群（最后观察结转）的协方差分析来评估抗精神病药和安慰剂的分离和试验脱落。在 6685 名参与者（90%为精神分裂症，10%为分裂情感障碍）中，初始严重程度与治疗的交互作用在 PANSS-30（β：-0.155；p<0.001）和所有 PANSS 子量表上均具有统计学意义（β范围：-0.097 至-0.135；p 值范围：<0.001 至 0.002）。在所有情况下，抗精神病药和安慰剂的差异都随着初始严重程度的增加而增加。从相对结果（剩余症状的百分比）分布来看，这种相互作用部分归因于反应机会的增加，但随着初始严重程度的增加，反应者的数值反应也更大，这也是原因之一。除了 PANSS-NEG 之外，所有 PANSS 量表的高初始严重程度都预示着试验脱落率的增加，尽管对于 PANSS-6 来说并不具有统计学意义。总之，我们复制了先前的发现，表明初始严重程度越大，抗精神病药和安慰剂的分离就越大，并将这些结果扩展到四个 PANSS 子量表。对于 PANSS-POS 和 PANSS-GEN，但对于 PANSS-NEG 和 PANSS-6 则不然，我们还复制了初始严重程度与试验脱落之间的关联。具有低初始阴性症状严重程度的患者被确定为一个特别值得进一步研究的群体，因为他们的结果在抗精神病药和安慰剂的分离（PANSS-NEG 测量的低分离）和试验脱落（高水平）方面与平均值的差异最大。
