Plasma concentrations of fluvoxamine and maprotiline in major depression: implications on therapeutic efficacy and side effects

Abstract

We examined the relationship between plasma concentrations of specific acting antidepressants (fluvoxamine/maprotiline) and clinical improvement as well as the impact of the magnitude of the plasma concentration of these antidepressants on side effects. Patients (32 patients with major depression) were treated within a double-blind parallel trial for four weeks and plasma concentrations were obtained before, on days 8 and 28 of the trial. Although there was a fixed-flexible dosage design it was apparent that 16 patients (89%) of the fluvoxamine group and all patients of the maprotiline group received a dosage between 200 and 300 mg/day in the last week of the trial. Plasma concentrations (mean +/- SD micrograms/l) of fluvoxamine were 125 +/- 91 and 142 +/- 108 on days 8 and 28, respectively and the range of fluvoxamine plasma concentrations on day 28 was from 20 to 417 micrograms/l. Plasma concentrations (mean +/- SD micrograms/l) of maprotiline were 146 +/- 62 and 202 +/- 134 on days 8 and 28, respectively and the range of maprotiline plasma concentration on day 28 was from 12 to 428 micrograms/l. There was no linear relationship between plasma concentrations of both antidepressants (fluvoxamine/maprotiline) and oral dosage. Whereas there was no correlation between fluvoxamine concentration and clinical response there was a tendency that higher maprotiline concentrations were associated with a better antidepressive efficacy at the end of the trial. Higher concentrations of fluvoxamine as well as of maprotiline were significantly (P < 0.05) associated with more side effects.