Plasma-level response relationships with fluoxetine and zimelidine.
The results of pharmacokinetic studies of two recent 5-HT uptake inhibitors, zimelidine and fluoxetine, have pointed to the inadequacy of open-dose rising studies for establishing the most appropriate dose of new antidepressants. High plasma concentrations of the active metabolites, norzimelidine and norfluoxetine, were associated with a poorer therapeutic response in patients suffering from major depression. High drug plasma concentrations are also associated with increased side effects. Large fixed-dose placebo controlled studies with fluoxetine have confirmed the findings of the small pharmacokinetic study that lower doses are more effective. Fixed-dose pharmacokinetic studies are recommended as part of the program to establish the best dose of new antidepressants.
Montgomery
S A
SA
Academic Department of Psychiatry, Medical School, St. Mary's Hospital, London, England.
Baldwin
D
D
Shah
A
A
Green
M
M
Fineberg
N
N
Montgomery
D
D
D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D015031:Zimeldine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use
D005473:Fluoxetine; D015031:Zimeldine