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. 2021 Aug;30(3):150-155.
Epub 2021 Aug 1.

Retrospective Review of Fluvoxamine-Clomipramine Combination Therapy in Obsessive-Compulsive Disorder in Children and Adolescents

Ryan Fung  1 , Dean Elbe  2 , S Evelyn Stewart  3
Affiliations

Retrospective Review of Fluvoxamine-Clomipramine Combination Therapy in Obsessive-Compulsive Disorder in Children and Adolescents

Ryan Fung et al. J Can Acad Child Adolesc Psychiatry. 2021 Aug.

Abstract
in English, French

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.

Objectifs: Préciser la posologie et décrire l’interaction pharmacocinétique, l’efficacité et l’innocuité de la thérapie combinée fluvoxamine-clomipramine pour le trouble obsessionnel-compulsif (TOC) pédiatrique réfractaire au traitement.

Méthodes: Une revue de dossiers rétrospective de patients souffrant du TOC à un hôpital pour enfants de soins tertiaires entre janvier 2010 et août 2017 a été menée. Les patients inclus avaient 18 ans ou moins lors de l’initiation de la thérapie combinée fluvoxamine-clomipramine et avaient au moins une série de valeurs de concentration sérique pour le captage des taux de clomipramine et de desméthylclomipramine.

Résultats: Six adolescents satisfaisaient aux critères d’inclusion de l’étude. La fluvoxamine inhibait adéquatement le métabolisme de la clomipramine pour la desméthylclomipramine de manière dose-dépendante. La thérapie combinée fluvoxamine-clomipramine était généralement bien tolérée sans effets indésirables sérieux ou dangereux déclarés.

Conclusion: La thérapie combinée fluvoxamine-clomipramine permet d’utiliser des doses plus faibles de clomipramine que celles habituellement utilisées en monothérapie de clomipramine et semble être une solution de rechange sûre pour les patients du TOC pédiatrique qui ne répondent pas aux essais de monothérapie d’inhibiteurs sélectifs séquentiels de recaptage de la sérotonine. La variabilité inter-patients et la cinétique saturable soutiennent le contrôle des médicaments thérapeutiques et des concentrations sériques de clomipramine et de desméthylclomipramine afin d’optimiser la thérapie. Un algorithme proposé qui correspond aux lignes directrices du traitement du TOC est décrit. Il faut d’autres études pour évaluer l’efficacité de cette approche.

Keywords: adolescent; clomipramine; fluvoxamine; obsessive-compulsive disorder; pediatric.

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Conflict of interest statement

Conflicts of Interest The authors have no financial relationships to disclose.

Figures

Figure 1
Figure 1
Semi-log plot of [DCMI]:[CMI] versus daily fluvoxamine dose
See this image and copyright information in PMC

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