Therapeutic reference range for duloxetine in the treatment of depression revised: a systematic review and meta-analysis

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For duloxetine, a therapeutic reference range (TRR) of 30–120 ng/ml is recommended to attain an optimal antidepressant effect [1]. However, the concentration-effect relationship, which forms the basis of the TRR, lacks systematic investigation. Therefore, the current range is considered preliminary. This review investigates the optimal target concentration for duloxetine’s antidepressant effects and identifies factors moderating its blood concentrations. A systematic literature review and meta-analysis was performed. Four databases were systematically searched for relevant articles reporting duloxetine concentrations in relation to clinical effects/side effects, pharmacokinetics, or receptor occupancy. 11 studies were eligible for qualitative analyses. Evidence for a positive relationship between blood concentrations and antidepressant effect was found in three studies; a concentration-dependent occurrence for the side effect irritability/anxiety was found in one study. Across four studies ( N =223), the population-based concentration ranges were 22–67 ng/ml. A threshold of 58 ng/ml was identified for clinical response. 75 percent of responders had blood concentrations below 123 ng/ml. PET studies reported 80% serotonin transporter occupancy at blood concentrations above 10–15 ng/ml, whereas 50% norepinephrine transporter occupancy were reported above 58 ng/ml. Smoking and specific medications led to significantly lower duloxetine blood concentrations. We suggest a TRR of 20–120 ng/ml for the antidepressant effect of duloxetine. Treatment effectiveness is likely influenced by smoking and specific comedications. This warrants a special indication for therapeutic drug monitoring of duloxetine, particularly when newly prescribed. Publication History Article published online: 12 March 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

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