Jakobsen Michelle Iris, Austin Stephen F, Storebø Ole Jakob, Simonsen Erik, Nielsen Jimmi
Department of Clinical Medicine, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark
Psychiatric Services Region Zealand East, Roskilde, Denmark.
BMJ Open. 2025 Mar 18;15(3):e093394. doi: 10.1136/bmjopen-2024-093394.
This study aimed to investigate the perspectives of clozapine-naïve outpatients with treatment-resistant schizophrenia on clozapine commencement and the barriers and facilitators of it.
A mixed-methods convergent design was employed using both qualitative and quantitative data on the same items.
In-home visits or meetings at three Mental Health outpatient facilities in Region Zealand East, Denmark.
Clozapine-eligible, yet clozapine-naïve, outpatients with schizophrenia. A convenience sample of 206 patients with schizophrenia treated with antipsychotic polypharmacy (APP) was screened for clozapine eligibility. Clozapine eligibility included recurrent/continued prescription of APP throughout the past year, ≥ 3 different antipsychotics (APs) trialled at a therapeutic dose and ≥2 APs trialled adequately before current treatment. All eligible patients able to provide written informed consent were invited to participate.
The participants' perspectives were assessed qualitatively through semistructured interviews and quantitatively with closed-ended questions, numerical scale ratings, and standardised patient-reported outcome measures. Moreover, the participants' sociodemographic and clinical characteristics were collected through case files, participant questionnaires, and clinical ratings made by the participants' treating clinicians. Interviews were transcribed verbatim and analysed thematically. Quantitative data were analysed with descriptive statistics. Finally, qualitative and quantitative results were compared and merged to draw meta-inferences.
Eighteen patients were included, 10 (56%) were men and the median age was 30.0 years (IQR 24.8-37.8). Nine participants (50%) were willing to commence clozapine if offered now, nine were not. No apparent clinical or socioeconomic differences were observed between refusers and acceptors; however, the acceptors rated their subjective recovery on the Brief INSPIRE-O significantly lower than the refusers did, and qualitatively, they all expressed subjective distress due to their current symptoms. Three themes characterised the refusers' reasons for not accepting clozapine: 'Reconciliation with the current situation warrants no change in treatment', 'Clozapine is a last-resort treatment for last-resort people' and 'Permanent or situational reluctance due to practical aspects of treatment'. In the vast majority of cases, blood sampling had little or no impact on the participants' current willingness to commence clozapine, and quantitatively, blood sampling ranked lowest of the suggested barriers, whereas hospital admission for clozapine commencement ranked highest. The adverse side effects of clozapine, sedation and, weight gain in particular, were considered a major barrier if previously encountered with ineffective AP trials. The introduction of individualised commencement plans mitigating personal barriers was highlighted as the facilitator with the greatest impact on clozapine willingness, able to turn refusals into acceptance.
Patients tend to prefer the predictability in status quo over switching to clozapine if they previously have trialled multiple APs with inadequate symptom reduction and subsequent deterioration/rehospitalisation or AP-induced weight gain and sedation. Moreover, the impression that clozapine treatment was unmanageable or a last-resort option further accentuated their reluctance to switch. Antipsychotic-trial fatigue and the stigma of clozapine as a last-resort treatment should be avoided by adhering to guidelines, thereby limiting the number of antipsychotics trialled before offering clozapine. Fortunately, it seems as if the patient's willingness to trial clozapine is positively impressionable to the conversation about customised commencement plans offering commencement on the patient's terms. For patients with subjective distress due to their symptoms, such plans can even reverse an initial clozapine refusalCite Now.
本研究旨在调查未使用过氯氮平的难治性精神分裂症门诊患者对开始使用氯氮平的看法以及相关的障碍和促进因素。
采用混合方法收敛性设计，对相同项目同时使用定性和定量数据。
丹麦西兰岛东部地区的三个精神卫生门诊机构进行家访或会面。
符合氯氮平使用条件但未使用过氯氮平的精神分裂症门诊患者。对206例接受抗精神病药物联合治疗（APP）的精神分裂症患者进行便利抽样，筛选其是否符合氯氮平使用条件。氯氮平使用条件包括在过去一年中持续/反复开具APP处方、在治疗剂量下试用过≥3种不同的抗精神病药物（AP）以及在当前治疗前充分试用过≥2种AP。邀请所有能够提供书面知情同意的符合条件的患者参与。
通过半结构化访谈对参与者的观点进行定性评估，并通过封闭式问题、数字量表评分和标准化的患者报告结局指标进行定量评估。此外，通过病例档案、参与者问卷以及参与者的治疗临床医生进行的临床评分收集参与者的社会人口学和临床特征。访谈逐字转录并进行主题分析。定量数据采用描述性统计进行分析。最后，对定性和定量结果进行比较和合并以得出综合推断。
纳入18例患者，10例（56%）为男性，中位年龄为30.0岁（四分位间距24.8 - 37.8）。9名参与者（50%）表示如果现在提供氯氮平愿意开始使用，9名则不愿意。拒绝者和接受者之间未观察到明显的临床或社会经济差异；然而，接受者在Brief INSPIRE - O上对主观康复的评分显著低于拒绝者，并且在定性方面，他们都因当前症状表达了主观痛苦。拒绝者不接受氯氮平的原因有三个主题：“与现状和解无需改变治疗”、“氯氮平是针对绝境之人的最后手段治疗”以及“由于治疗实际方面的永久性或情境性不情愿”。在绝大多数情况下，采血对参与者当前开始使用氯氮平的意愿影响很小或没有影响，在定量方面，采血在建议的障碍中排名最低，而因氯氮平开始治疗而住院排名最高。如果之前在无效的AP试验中遇到过，氯氮平的不良副作用，尤其是镇静和体重增加，被认为是一个主要障碍。引入减轻个人障碍的个性化开始计划被强调为对氯氮平意愿影响最大的促进因素，能够将拒绝转变为接受。
如果患者之前试用过多种AP但症状减轻不足且随后病情恶化/再次住院或出现AP引起的体重增加和镇静，他们往往更喜欢现状的可预测性而非改用氯氮平。此外，认为氯氮平治疗难以管理或作为最后手段选择的印象进一步加剧了他们改用的不情愿。应遵循指南避免抗精神病药物试验疲劳以及氯氮平作为最后手段治疗的污名化，从而限制在提供氯氮平之前试用的抗精神病药物数量。幸运的是，患者试用氯氮平的意愿似乎对关于根据患者条件提供个性化开始计划的谈话有积极的易感性。对于因症状而有主观痛苦的患者，这样的计划甚至可以扭转最初对氯氮平的拒绝。立即引用。
