J Clin Psychopharmacol. 2018 Jun;38(3):234-238. doi: 10.1097/JCP.0000000000000860.
PURPOSE/BACKGROUND: The use of clozapine, particularly in young people, is often limited by early treatment-emergent adverse effects including drowsiness and lethargy. Concerns about adverse effects, medication adherence, and the need for blood monitoring often impede the use of clozapine in this population, leading to repeated trials of less effective medications. Current clozapine dosing recommendations are based on people further in the course of their illness and thus reflect different responsiveness and sensitivities to antipsychotic medication. As such, there is a need for evidence-based guidelines for titration and dosing of clozapine among people in early psychosis.
METHODS/PROCEDURES: We performed a chart review of 14 people treated with clozapine within our early psychosis team. Data regarding dose titration, response, time to discontinuation, symptom severity, weight gain, and other adverse effects were gathered at clozapine initiation, 3 months, and last available visit on clozapine.
FINDINGS/RESULTS: People treated with slow titration within their first year of psychosis onset achieved sustained response at very low maintenance doses (mean dose = 81 mg/d, mean duration of treatment = 200 weeks) compared with slow titration with longer duration of illness (mean dose = 350 mg/d, mean duration of treatment = 68 weeks) or standard dose titration in early psychosis (mean dose = 112 mg/d, mean duration of treatment = 38 weeks). The most common adverse effects in all groups were weight gain and sedation, with the groups requiring higher mean doses reporting a broader range of adverse effects. There was no apparent difference in the clinical global impression for severity or improvement between the slow titration and standard titration groups in people with early psychosis. These observations are synthesized into a proposed treatment guideline for use of clozapine among people in early psychosis.
IMPLICATIONS/CONCLUSIONS: We describe development of a slow titration approach to initiating clozapine among people in early psychosis. This approach resulted in clinical response at remarkably low maintenance doses of clozapine among people within their first year of illness, but not in those with longer duration of symptoms. Slow titration also led to good tolerability and acceptance of clozapine treatment for some patients.
目的/背景：氯氮平的使用，特别是在年轻人中，常常受到早期治疗出现的不良反应的限制，包括嗜睡和昏睡。对不良反应、药物依从性和血液监测的担忧常常阻碍了该人群使用氯氮平，导致反复尝试使用效果较差的药物。目前的氯氮平剂量推荐是基于疾病进展更后期的人群，因此反映了对抗精神病药物的不同反应性和敏感性。因此，需要有针对早期精神病患者氯氮平滴定和剂量的循证指南。
方法/程序：我们对我们的早期精神病团队中接受氯氮平治疗的 14 人进行了图表回顾。在氯氮平开始时、3 个月和最后一次可用的氯氮平就诊时，收集了剂量滴定、反应、停药时间、症状严重程度、体重增加和其他不良反应的数据。
结果/发现：在精神病发病的第一年接受缓慢滴定的患者，在极低的维持剂量（平均剂量=81mg/d，平均治疗时间=200 周）下实现了持续反应，而在疾病持续时间较长的缓慢滴定（平均剂量=350mg/d，平均治疗时间=68 周）或早期精神病的标准剂量滴定中（平均剂量=112mg/d，平均治疗时间=38 周）则不然。所有组中最常见的不良反应是体重增加和镇静，需要更高平均剂量的组报告了更广泛的不良反应。在早期精神病患者中，缓慢滴定组和标准滴定组之间的临床总体印象严重程度或改善程度没有明显差异。这些观察结果综合为早期精神病患者氯氮平使用的建议治疗指南。
意义/结论：我们描述了一种在早期精神病患者中缓慢滴定氯氮平的方法。这种方法在疾病发病的第一年，使氯氮平的维持剂量非常低，就能达到临床反应，但在症状持续时间较长的患者中则不然。缓慢滴定也导致了一些患者对氯氮平治疗的良好耐受性和接受度。
