Venlafaxine serum concentrations in children and adolescents – preliminary results of a multicenter Therapeutic Drug Monitoring trial

Venlafaxine is approved in adults to treat depression, anxiety or panic disorders, while its use in children and adolescents is off-label. Our study aimed to examine the relationship between dose and serum levels of venlafaxine and its active metabolite O-desmethylvenlafaxine (active moiety, AM) to explore a potential age- and indication- specific therapeutic reference range (TRR) in pediatric patients.

Steady state serum concentrations of AM venlafaxine were measured in 104 patients (76% female, mean age 15.9 years) as part of a Therapeutic Drug Monitoring service and within the TDM-VIGIL pharmacovigilance trial. Clinical outcome was assessed by the Clinical Global Impression Scale; side effects by the Udvalg for Kliniske Undersogelser-Side Effect Rating Scale.

The study showed a positive correlation between dose and serum concentrations of AM venlafaxine (rho= 0.515, p< 0.001). 63.5% of the serum levels lied within the proposed TRR for adults (100 –400 ng/ml). Parameters like age, sex, and comedication did not significantly influence serum levels. 21.5% of the patients were rated as responders (3.9% very much improved, 17.6% much improved), 78.4% were reported as minimally improved. More than half of the patients experienced no adverse effects (54.9%). The determined age-specific TRR for venlafaxine in children and adolescents ranged between 100-381 ng/ml (mean serum level +/- SD) or between 145-294 ng/ml (25th-75th percentile) and thus within the recommended range for adults.

In summary, the TRR established for adults, especially the upper limit, should be used with caution in children and adolescents. Further studies with larger samples and under controlled conditions are needed to confirm our results.

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Artikel online veröffentlicht:
12. März 2024