Pharmacology & Therapeutics, University of British Columbia.
Departments of Psychiatry.
J Clin Psychopharmacol. 2021;41(2):186-190. doi: 10.1097/JCP.0000000000001342.
Although clozapine is the gold standard for treatment-resistant schizophrenia, more than 30% of patients remain unresponsive to clozapine monotherapy and may benefit from augmentation strategies. Fluvoxamine augmentation of clozapine may be beneficial in treatment resistance because of pharmacokinetic interactions, allowing for lower clozapine dosages with higher clozapine serum levels and an increased clozapine-to-norclozapine ratio, which can modify adverse effects. An augmentation strategy using higher fluvoxamine doses may also improve persistent negative, anxiety, and obsessive-compulsive symptoms through fluvoxamine's serotonergic activity.
Through chart review, we identified 4 cases of patients with treatment-resistant psychosis who underwent high-dose fluvoxamine augmentation of clozapine to target residual negative symptoms, refractory psychosis, anxiety, and obsessive-compulsive symptoms.
This augmentation strategy continued in 2 patients after discharge who showed clinical improvement without significant adverse effects. Two patients experienced adverse effects that led to the fluvoxamine discontinuation. Despite the fact that fluvoxamine augmentation led to symptom improvement in only 2 patients, all patients achieved high serum clozapine levels. Hematologic parameters were monitored in all patients, and no abnormalities were observed. No severe adverse effects of clozapine were experienced.
Although high variability of responses and adverse effects were observed during fluvoxamine augmentation to clozapine, this strategy was successful in increasing clozapine serum levels. Through fluvoxamine's serotonergic effects, this strategy may confer benefit to residual negative, obsessive, and anxiety symptoms. Limitations of this case series include the retrospective nature, absence of controls, diversity of diagnoses, multiple interventions in each patient, and lack of masked raters.
氯氮平虽然是治疗抵抗性精神分裂症的金标准，但仍有 30%以上的患者对氯氮平单药治疗无反应，可能受益于增效策略。由于药代动力学相互作用，氟伏沙明增效氯氮平可能对治疗抵抗有益，允许更低的氯氮平剂量和更高的氯氮平血清水平，并增加氯氮平-去甲氯氮平的比值，从而改变不良反应。使用更高氟伏沙明剂量的增效策略也可能通过氟伏沙明的 5-羟色胺能活性改善持续性阴性、焦虑和强迫症状。
通过病历回顾，我们确定了 4 例治疗抵抗性精神病患者，他们接受了高剂量氟伏沙明增效氯氮平以针对残留的阴性症状、难治性精神病、焦虑和强迫症状。
这一增效策略在 2 名出院后继续使用的患者中持续进行，他们表现出临床改善，没有明显的不良反应。两名患者出现不良反应，导致氟伏沙明停药。尽管氟伏沙明增效仅使 2 名患者症状改善，但所有患者均达到了较高的氯氮平血清水平。所有患者均监测了血液学参数，未观察到异常。没有出现氯氮平的严重不良反应。
尽管在氟伏沙明增效氯氮平过程中观察到反应和不良反应的高度变异性，但这一策略成功地增加了氯氮平的血清水平。通过氟伏沙明的 5-羟色胺能作用，这一策略可能对残留的阴性、强迫和焦虑症状有益。本病例系列的局限性包括回顾性、缺乏对照、诊断多样性、每位患者的多种干预措施以及缺乏盲法评估者。
