title: Pharmacokinetics and efficacy of fluvoxamine and amitriptyline in depression.
abstract: Although often necessary for obtaining remission following major depressive disorder, combined antidepressant treatment is frequently associated with drug interactions and enhanced adverse drug effects. We investigated pharmacokinetic interactions following combined fluvoxamine and amitriptyline treatment and their impact on therapeutic efficacy and tolerability. Twenty-two inpatients with major depression [Hamilton Depression Scale (HAM-D) rating > or =18] were treated with either amitriptyline (75 mg/day), fluvoxamine (100 mg/day) or both. Blood samples, for determination of amitriptyline, its major metabolite nortritpyline, and fluvoxamine, were obtained after single dose administration and in steady-state. Therapeutic efficacy was evaluated using HAM-D and adverse drug effects were evaluated using the clinical global impression scale. Following combined treatment, steady-state plasma levels of nortriptyline were significantly decreased compared to monotherapy. HAM-D scores after two-week treatment showed that there was a better response to combined treatment. There was no significant difference in severity of adverse effects among groups. We observed a pharmacokinetic interaction between fluvoxamine and amitritpyline resulting in impaired metabolism of the later. However, no significant impact of the interaction on treatment safety was observed. Moreover, concomitant use of amitriptyline at 75 mg/day and fluvoxamine at 100 mg/day was well tolerated with a more prompt and stronger onset of clinical response compared to monotherapy in patients with major depression.
authors.affiliation: Department of Pharmacokinetics, Faculty of Pharmacy, University of Belgrade, Serbia. svezmar@pharmacy.bg.ac.rs
authors.forename: Sandra
authors.initials: S
authors.lastname: Vezmar
authors.forename: Branislava
authors.initials: B
authors.lastname: Miljkovic
authors.forename: Katarina
authors.initials: K
authors.lastname: Vucicevic
authors.forename: Ivana
authors.initials: I
authors.lastname: Timotijevic
authors.forename: Milica
authors.initials: M
authors.lastname: Prostran
authors.forename: Zoran
authors.initials: Z
authors.lastname: Todorovic
authors.forename: Milena
authors.initials: M
authors.lastname: Pokrajac
mesh_terms: D000328:Adult; D000639:Amitriptyline / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D016666:Fluvoxamine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D016666:Fluvoxamine