Fung Ryan, Elbe Dean, Stewart S Evelyn
Clinical Pharmacist, Saskatchewan Health Authority, Saskatoon, Saskatchewan (at time of study, Pharmacy Resident, Department of Pharmacy, Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia).
Clinical Pharmacy Specialist, Department of Pharmacy, Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia; Child and Adolescent Mental Health Programs, BC Children's Hospital, Vancouver, British Columbia; Department of Psychiatry, University of British Columbia, Vancouver, British Columbia.
J Can Acad Child Adolesc Psychiatry. 2021 Aug;30(3):150-155. Epub 2021 Aug 1.
To inform dosing and describe the pharmacokinetic interaction, efficacy and safety of fluvoxamine-clomipramine combination therapy for treatment-resistant pediatric obsessive-compulsive disorder (OCD).
A retrospective chart review of OCD-affected patients at a tertiary care children's hospital between January 2010 and August 2017 was conducted. Those included were 18 years of age or younger at initiation of fluvoxamine-clomipramine combination therapy and had at least one set of serum concentration values capturing clomipramine and desmethylclomipramine levels.
Six adolescents met study inclusion criteria. Fluvoxamine adequately inhibited clomipramine metabolism to desmethylclomipramine in a dose-dependent manner. Fluvoxamine-clomipramine combination therapy was generally well tolerated with no serious or life-threatening adverse effects reported.
Fluvoxamine-clomipramine combination therapy permits use of lower clomipramine doses than typically used as clomipramine monotherapy and appears to be a safe alternative for pediatric OCD patients failing sequential selective serotonin reuptake inhibitor monotherapy trials. Inter-patient variability and saturable kinetics support therapeutic drug monitoring of serum clomipramine and desmethylclomipramine concentrations to optimize therapy. A proposed algorithm that aligns with current OCD treatment guidelines is described. Further study is needed to evaluate efficacy of this approach.
为难治性儿童强迫症(OCD)的氟伏沙明-氯米帕明联合治疗提供用药剂量信息,并描述其药代动力学相互作用、疗效和安全性。
对一家三级护理儿童医院2010年1月至2017年8月期间受强迫症影响的患者进行回顾性病历审查。纳入的患者在开始氟伏沙明-氯米帕明联合治疗时年龄为18岁或以下,并且至少有一组血清浓度值记录了氯米帕明和去甲氯米帕明的水平。
六名青少年符合研究纳入标准。氟伏沙明以剂量依赖的方式充分抑制氯米帕明代谢为去甲氯米帕明。氟伏沙明-氯米帕明联合治疗总体耐受性良好,未报告严重或危及生命的不良反应。
与通常作为氯米帕明单一疗法使用的剂量相比,氟伏沙明-氯米帕明联合治疗允许使用更低剂量的氯米帕明,并且对于在序贯选择性5-羟色胺再摄取抑制剂单一疗法试验中失败的儿童强迫症患者似乎是一种安全的替代方案。患者间的变异性和饱和动力学支持对血清氯米帕明和去甲氯米帕明浓度进行治疗药物监测以优化治疗。描述了一种与当前强迫症治疗指南一致的建议算法。需要进一步研究来评估这种方法的疗效。