Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, PO63, De Crespigny Park, London SE5 8AF, UK.
National Psychosis Service, South London, and Maudsley NHS Foundation Trust, London, United Kingdom.
J Clin Psychiatry. 2019 Sep 24;80(5):18m12716. doi: 10.4088/JCP.18m12716.
Clozapine is the only medication approved for those patients with schizophrenia who do not achieve a clinical response to standard antipsychotic treatment, yet it is still underused. Furthermore, in the case of a partial or minimal response to clozapine treatment, there is no clarity on the next pharmacologic intervention.
The National Psychosis Service is a tertiary referral inpatient unit for individuals with refractory psychosis. Data from 2 pooled data sets (for a total of 325 medical records) were analyzed for treatment trajectories between admission and discharge (2001-2016). Effectiveness of pharmacologic treatment was determined using change in symptoms, assessed using the Operational Criteria (OPCRIT) system applied retrospectively to the medical records. Analysis was focused on identifying the optimal medication regimens impacting clinical status during the admission.
Less than a quarter of the patients were on clozapine treatment at the time of admission; this rate increased to 63.4% at the time of discharge. Initiating clozapine during admission (n = 136) was associated with a 47.9% reduction of symptoms as reflected by their OPCRIT score. In cases in which clozapine monotherapy did not achieve sufficient improvement in symptoms, the most effective clozapine augmentation strategy was adding amisulpride (n = 22, 60.8% reduction of symptoms), followed by adding a mood stabilizer (n = 36, 53.7% reduction). A less favorable option was addition of quetiapine (n = 15, 26.7% reduction).
Many people with longer-term and complex refractory illness do respond to clozapine treatment with suitable augmentation strategies when necessary. Furthermore, it is possible to advance clozapine prescribing in these complex patients when they are supported by a skilled and dedicated multidisciplinary team. The optimal therapeutic approach relies on confirmation of diagnosis and compliance and optimization of clozapine dose using therapeutic drug monitoring, followed by augmentation of clozapine with amisulpride or mood stabilizers. There is some preliminary evidence suggesting that augmentation strategies may impact differentially depending on the symptom profile.
氯氮平是唯一一种被批准用于那些对标准抗精神病药物治疗无临床反应的精神分裂症患者的药物，但它的使用仍然不足。此外，对于氯氮平治疗的部分或最小反应，对于下一次药物干预还没有明确的认识。
国家精神病服务机构是一个三级转诊住院单位，为难治性精神病患者提供服务。对 2 个汇总数据集（共 325 份病历）中的治疗轨迹进行分析，从入院到出院（2001-2016 年）。使用症状变化来确定药物治疗的效果，使用回溯性应用于病历的操作标准（OPCRIT）系统进行评估。分析的重点是确定在入院期间影响临床状况的最佳药物治疗方案。
入院时，不到四分之一的患者接受氯氮平治疗；在出院时，这一比例上升到 63.4%。入院时开始氯氮平治疗（n=136）与 OPCRIT 评分反映的症状减少 47.9%有关。在氯氮平单一治疗不能显著改善症状的情况下，最有效的氯氮平增效策略是添加氨磺必利（n=22，症状减少 60.8%），其次是添加情绪稳定剂（n=36，症状减少 53.7%）。添加喹硫平是一个不太理想的选择（n=15，症状减少 26.7%）。
许多患有长期和复杂难治性疾病的患者在必要时会对氯氮平治疗有反应，并且可以在由技能熟练和专注的多学科团队支持的情况下推进对这些复杂患者的氯氮平处方。最佳治疗方法依赖于确诊和遵从性，以及使用治疗药物监测优化氯氮平剂量，然后使用氨磺必利或情绪稳定剂来增强氯氮平的效果。有一些初步的证据表明，增效策略可能会根据症状谱的不同而产生不同的影响。
