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, li thium is often added to the antidepressant for augmentation. The present st udy 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 an d 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 c arbonate (16 meg Li+) for 10 days at 08.00 h and a single oral dose of 30 m g mirtazapine at 21.00 h on day 9 or the same number (n = 4) of placebo cap sules 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 mirta zapine plasma concentrations and lithium serum concentrations. In addition, psychometric tests were performed and the safety and tolerability of the d rugs were assessed. The results indicate that mirtazapine does not alter th e pharmacokinetics of lithium and vice versa. In addition, the combination of mirtazapine and lithium appeared to be safe and well-tolerated. Extensiv e psychometric testing after the administration of mirtazapine did not reve al any differences on any tests in subjects on lithium and placebo, respect ively.