Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database.
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.
Reis
Margareta
M
Department of Forensic Chemistry and Genetics, Swedish National Board of Forensic Medicine, Linköping, Sweden. margareta.reis@med.lu.se
Aamo
Trond
T
Spigset
Olav
O
Ahlner
Johan
J
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000097:blood* / Q000493:pharmacokinetics; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000493:pharmacokinetics; D001711:Biotransformation; D002648:Child; D002851:Chromatography, High Pressure Liquid; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D014179:Neurotransmitter Uptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D009664:Norway / Q000453:epidemiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D012737:Sex Factors; D055815:Young Adult
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D014179:Neurotransmitter Uptake Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors