Yusufi Babur, Mukherjee Sujoy, Flanagan Robert, Paton Carol, Dunn Graham, Page Eleanor, Barnes Thomas R E
West London Mental Health NHS Trust, Guy's and St Thomas' NHS Foundation Trust, Department of Psychological Medicine, London, UK.
Int Clin Psychopharmacol. 2007 Jul;22(4):238-43. doi: 10.1097/YIC.0b013e32819f8f17.
Clozapine is associated with non-neurological side effects that can be subjectively unpleasant and/or clinically serious. We sought to: (i) assess the nature and prevalence of side effects experienced by patients receiving maintenance treatment with clozapine and (ii) explore the relationship between clozapine plasma concentration and side effect burden. Patients were receiving clozapine maintenance treatment. Open questioning followed by systematic enquiry using the Antipsychotic Non-neurological Side Effects Rating Scale were used to assess side effects. Trough plasma clozapine and norclozapine concentrations were measured. One hundred and three patients participated. On open questioning, 61 patients reported a total of 117 side effects, whereas systematic enquiry identified an additional 649 side effects, with each patient reporting at least one. Clozapine plasma concentrations were significantly but weakly correlated with total Antipsychotic Non-neurological Side Effects Rating Scale score (Pearson correlation=0.29, P<0.004). Patients with a plasma clozapine concentration >0.25 mg/l were significantly more likely to have moderate/severe side effects than patients with lower plasma concentrations (63/76 vs. 12/23, chi=9.07, d.f.=1, P<0.01). The side-effect burden associated with maintenance clozapine treatment is high and the true extent can only be ascertained by systematic inquiry. The use of target plasma concentrations below those used for acute treatment should be explored as a strategy for minimizing side effects.
氯氮平与非神经方面的副作用相关，这些副作用可能在主观上令人不适和/或在临床上较为严重。我们旨在：（i）评估接受氯氮平维持治疗的患者所经历的副作用的性质和发生率，以及（ii）探究氯氮平血药浓度与副作用负担之间的关系。患者正在接受氯氮平维持治疗。采用开放性询问，随后使用抗精神病药物非神经副作用评定量表进行系统询问来评估副作用。测量了氯氮平及去甲氯氮平的血药谷浓度。103名患者参与了研究。在开放性询问中，61名患者报告了总共117种副作用，而系统询问又发现了另外649种副作用，每名患者至少报告了一种。氯氮平血药浓度与抗精神病药物非神经副作用评定量表总分显著但微弱相关（Pearson相关系数=0.29，P<0.004）。血药氯氮平浓度>0.25mg/l的患者出现中度/重度副作用的可能性显著高于血药浓度较低的患者（63/76 vs. 12/23，卡方值=9.07，自由度=1，P<0.01）。与氯氮平维持治疗相关的副作用负担很高，只有通过系统询问才能确定其真实程度。应探索使用低于急性治疗时的目标血药浓度作为减少副作用的一种策略。
