Serum Concentrations of Antidepressant Drugs in a Naturalistic Setting: Compilation Based on a Large Therapeutic Drug Monitoring Database

Abstract

A compilation of therapeutic drug monitoring data for 15 antidepressant drugs in a naturalistic routine clinical setting is presented. A substantial number of serum concentrations, at different daily doses, are outlined, and the intraindividual and overall serum concentration coefficient of variation for a respective substance is presented. Also, concentration comparisons between women and men, and patients older or younger than 65 years are made. The drugs included are amitriptyline (n = 394), citalopram (n = 5457), clomipramine (n = 400), escitalopram (n = 3066), fluoxetine (n = 793), fluvoxamine (n = 165), mianserin (n = 1063), mirtazapine (n = 1427), moclobemide (n = 200), nortriptyline (n = 206), paroxetine (n = 1677), reboxetine (n = 85), sertraline (n = 2998), trimipramine (n = 158), and venlafaxine (n = 1781). Of the 9 drugs exhibiting linear (first order) kinetics, all but reboxetine gave a significant negative dose-to-dose-normalized correlation with concentrations, that is an increased clearance with higher dose. When dose was correlated to the metabolite:parent substance ratio for drugs exhibiting linear kinetics, citalopram and mianserin gave a positive slope, contrary to a negative slope shown for sertraline and venlafaxine. The intraindividual variations of the serum concentrations were lower than the overall variations, and the intraindividual variation of the metabolite:parent substance ratio was lower than the intraindividual variation of respective parent substance (except clomipramine and mianserin). Women had significantly higher serum concentrations than men (significant for citalopram, escitalopram, mianserin, mirtazapine, and venlafaxine), and patients older than 65 years had higher serum concentrations than the younger ones for all drugs except amitriptyline, moclobemide, and trimipramine. By presenting a comprehensive compilation of therapeutic drug monitoring data for each drug, a reference tool is created, in addition to improved pharmacokinetic knowledge of antidepressant drugs.

Effects on enantiomeric drug disposition and open-field behavior after chronic treatment with venlafaxine in the P-glycoprotein knockout mice model

“…In another TDM study, an Odm-venlafaxine/venlafaxine ratio of 2.5 was reported (Reis et al 2009). Compared to humans, the mice in the present study displayed higher concentrations of Ndm-venlafaxine in relation to Odm-venlafaxine (Odmvenlafaxine/Ndm-venlafaxine ratio: 0.08 in mice and 2.5 in humans) (Reis et al 2002).…”

Editor’s Highlight: Therapeutic Concentrations of Antidepressants Inhibit Pancreatic Beta-Cell Function via Mitochondrial Complex Inhibition

“…, 1997;Rubin et al, 2008;Brown et al, 2008;Derijks et al, 2008;Andersohn et al, 2009;Kivimäki et al, 2010;Khoza et al, 2011).…”

“…Importantly, adverse metabolic effects were seen at chronic AD concentrations of 100 nM; a value less than the median therapeutic concentration for most dosage regimens (Reis et al, 2009). Moreover, as the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 plasma concentration for these ADs are well established to be related to dose (Reis et al, 2009), a daily fluoxetine dose of 80 mg can yield steady state plasma concentrations >2 µM (Lundmark et al, 2001), a concentration sufficient to disrupt beta-cell mitochondrial bioenergetics.…”

“…However, clinical studies indicate that the tricyclic antidepressant (TCA) and serotonin selective reuptake inhibitor (SSRI) classes of AD are particularly associated with increased risks of hyperglycaemia and type 2 diabetes mellitus (T2D) (Lustman et al, 1997;Rubin et al, 2008;Brown et al, 2008;Derijks et al, 2008;Andersohn et al, 2009;Kivimäki et al, 2010;Khoza et al, 2011). Although weight gain is a common side effect of AD usage (Uguz et al, 2015) and a risk factor for T2D (Andersohn et al, 2009;Kivimäki et al, 2010;), when weight is controlled for, ADs still increase T2D risk (Rubin et al, 2008;Pan et al, 2012).…”

Kjønns- og aldersforskjeller ved bruk av psykofarmaka

“…Dette er i overensstemmelse med en tidligere norsk studie der serumkonsentrasjon av flere antidepressiver ble rapportert å vaere signifikant høyere hos kvinner og hos eldre pasienter sammenliknet med menn og yngre pasienter (5). Studiene tyder på en endret farmakokinetikk av antidepressiver hos eldre kvinner.…”