Pharmacokinetics of mirtazapine and lithium in healthy male subjects.
A substantial proportion of patients diagnosed with depression and treated with antidepressants show no or insufficient response. In such patients, lithium is often added to the antidepressant for augmentation. The present study investigated the possible drug-drug interaction between mirtazapine and lithium in 12 healthy male subjects in a randomized, double-blind, placebo-controlled two-period cross-over design. Subjects meeting the inclusion and exclusion criteria were randomly assigned to one of two groups. After an overnight fast, they received either a single oral dose of 600 mg lithium carbonate (16 meq Li+) for 10 days at 08.00 h and a single oral dose of 30 mg mirtazapine at 21.00 h on day 9 or the same number (n = 4) of placebo capsules and and a single oral dose of 30 mg mirtazapine at 21.00 h on day 9. At pre-defined times, blood samples were drawn for the measurement of mirtazapine plasma concentrations and lithium serum concentrations. In addition, psychometric tests were performed and the safety and tolerability of the drugs were assessed. The results indicate that mirtazapine does not alter the pharmacokinetics of lithium and vice versa. In addition, the combination of mirtazapine and lithium appeared to be safe and well-tolerated. Extensive psychometric testing after the administration of mirtazapine did not reveal any differences on any tests in subjects on lithium and placebo, respectively.
Sitsen
J M
JM
Clinical Development Department, NV Organon, Oss, The Netherlands. j.sitsen@organon.oss.akzonobel.nl
Voortman
G
G
Timmer
C J
CJ
D000293:Adolescent; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008094:Lithium / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008875:Middle Aged; D000078785:Mirtazapine; D011594:Psychometrics
D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D008094:Lithium; D000078785:Mirtazapine