Michael Paulzen1, Ekkehard Haen2, Christoph Hiemke3, Bianca Fay2, Sandra Unholzer2, Gerhard Gründer4, Georgios Schoretsanitis5. 1. Alexianer Hospital Aachen, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, Aachen, Germany. 2. Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany. 3. Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Germany. 4. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, Aachen, Germany. 5. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, Aachen, Germany; University Hospital of Psychiatry, Bern, Switzerland. Electronic address: george.schor@gmail.com.
Abstract
BACKGROUND: To uncover pharmacokinetic interactions between venlafaxine and doxepin or mirtazapine in a naturalistic sample. METHODS: A therapeutic drug monitoring database containing plasma concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODVEN) was analyzed. We included 1067 of 1594 patients in the analysis. Three study groups were considered; a group of patients under venlafaxine without confounding medications, V0 (n = 905), a group of patients co-medicated with doxepin, VDOX (n = 25) and a second group, co-medicated with mirtazapine, VMIR, n = 137. Plasma concentrations of VEN, ODVEN and the clinically relevant active moiety, sum of venlafaxine and O-desmethylvenlafaxine (ODVEN) (AM), as well as dose-adjusted plasma concentrations (C/D) were compared. RESULTS: Median concentrations in the doxepin group showed 57.7% and 194.4% higher values for AM and VEN respectively; these differences were statistically significant (p < 0.001 for AM and p = 0.002 for VEN). Similar differences were detected for C/D concentrations of active moiety and VEN (p < 0.001 and p = 0.001) with higher values also in the doxepin group. The ratios ODVEN/VEN were lower in the doxepin group (p < 0.001). A co-medication with mirtazapine did not cause any changes in venlafaxine metabolism. CONCLUSIONS: Higher concentrations for VEN and AM imply an inhibiting effect of doxepin on the metabolism of venlafaxine, although the huge variability of concentrations has to be taken into account. It is recommended to monitor plasma concentrations in combination treatment to avoid problems in safety and efficacy. LIMITATIONS: Despite the large size of our study sample, the naturalistic nature of this data may arise some concerns of information bias potentially resulting from non-standardized data recording.
BACKGROUND: To uncover pharmacokinetic interactions between venlafaxine and doxepin or mirtazapine in a naturalistic sample. METHODS: A therapeutic drug monitoring database containing plasma concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODVEN) was analyzed. We included 1067 of 1594 patients in the analysis. Three study groups were considered; a group of patients under venlafaxine without confounding medications, V0 (n = 905), a group of patients co-medicated with doxepin, VDOX (n = 25) and a second group, co-medicated with mirtazapine, VMIR, n = 137. Plasma concentrations of VEN, ODVEN and the clinically relevant active moiety, sum of venlafaxine and O-desmethylvenlafaxine (ODVEN) (AM), as well as dose-adjusted plasma concentrations (C/D) were compared. RESULTS: Median concentrations in the doxepin group showed 57.7% and 194.4% higher values for AM and VEN respectively; these differences were statistically significant (p < 0.001 for AM and p = 0.002 for VEN). Similar differences were detected for C/D concentrations of active moiety and VEN (p < 0.001 and p = 0.001) with higher values also in the doxepin group. The ratios ODVEN/VEN were lower in the doxepin group (p < 0.001). A co-medication with mirtazapine did not cause any changes in venlafaxine metabolism. CONCLUSIONS: Higher concentrations for VEN and AM imply an inhibiting effect of doxepin on the metabolism of venlafaxine, although the huge variability of concentrations has to be taken into account. It is recommended to monitor plasma concentrations in combination treatment to avoid problems in safety and efficacy. LIMITATIONS: Despite the large size of our study sample, the naturalistic nature of this data may arise some concerns of information bias potentially resulting from non-standardized data recording.
Authors: H H Stassen; S Bachmann; R Bridler; K Cattapan; D Herzig; A Schneeberger; E Seifritz Journal: Eur Arch Psychiatry Clin Neurosci Date: 2021-11-25 Impact factor: 5.760
Authors: H H Stassen; S Bachmann; R Bridler; K Cattapan; D Herzig; A Schneeberger; E Seifritz Journal: Eur Arch Psychiatry Clin Neurosci Date: 2020-07-21 Impact factor: 5.270