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

OBJECTIVESTo inform dosing and describe the pharmacokinetic interaction, efficacy and safety of fluvoxamine-clomipramine combination therapy for treatment-resistant pediatric obsessive-compulsive disorder (OCD). METHODSA 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. RESULTSSix 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. CONCLUSIONFluvoxamine-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.