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Increased trimipramine plasma levels during fluvoxamine comedication

E Seifritz¹, E Holsboer-Trachsler, U Hemmeter

¹Psychiatric University Hospital, Department of Psychiatry, University of Basel, Switzerland.

European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology

|March 1, 1994

Summary

Drug interactions between trimipramine and citalopram or fluvoxamine worsened depression and caused panic attacks in a patient. Fluvoxamine significantly increased trimipramine levels, suggesting cytochrome P450 enzyme interactions.

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Area of Science:

Pharmacology
Neuroscience
Clinical Psychiatry

Background:

Trimipramine (TRI) is a tricyclic antidepressant.
Selective serotonin reuptake inhibitors (SSRIs) like citalopram (CIT) and fluvoxamine (FLUV) are commonly used for depression.
Drug-drug interactions can alter antidepressant efficacy and safety.

Observation:

A patient, initially unresponsive to TRI, experienced worsening depression and panic attacks upon co-administration with CIT and later with FLUV.
Adding FLUV to TRI treatment doubled TRI plasma levels and slightly increased its metabolites.
The patient was phenotyped as an extensive metabolizer for dextromethorphan and mephenytoin.

Findings:

Fluvoxamine (FLUV) significantly inhibited the metabolism of trimipramine (TRI), increasing its plasma concentration.

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The interaction likely involved cytochrome P450 enzymes, specifically CYP2D6 and CYP3A4 (implied by mephenytoin metabolism).

Adverse effects suggest a pharmacokinetic interaction and potential alterations in neurotransmitter systems.

Implications:

Clinicians should exercise caution when co-administering fluvoxamine with trimipramine due to potential for significant drug interactions.
Understanding individual cytochrome P450 enzyme activity is crucial for predicting and managing antidepressant drug interactions.
Further research is needed to elucidate the precise mechanisms of these interactions and their impact on serotonergic and dopaminergic pathways.