Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent · 2021
Retrospective Review of Fluvoxamine-Clomipramine Combination Therapy in Obsessive-Compulsive Disorder in Children and Adolescents.
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Fung Ryan, Elbe Dean, Stewart S Evelyn
Аннотация
OBJECTIVES: To inform dosing and describe the pharmacokinetic interaction, efficacy and safety of fluvoxamine-clomipramine combination therapy for treatment-resistant pediatric obsessive-compulsive disorder (OCD).
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.