International dosage differences in fluoxetine clinical trials.
OBJECTIVE
International differences are thought to exist in dosages used by clinicians treating mood disorders. This study examined international dosage differences in antidepressant clinical trials, using a database formed and maintained as a component of a Cochrane review of comparative clinical trials of fluoxetine.


METHODS
This systematic review included 132 studies. A detailed set of methodological features and results were abstracted from the original publications and entered into an electronic database. Mean and maximum fluoxetine dosages were compared across countries. To evaluate the dosages of comparison medications, a defined daily dosage (DDD) ratio was calculated as the trial mean dosage divided by the DDD for that drug.


RESULTS
Both the maximum and mean dosages for fluoxetine and comparison medications were higher in trials conducted in the US (fluoxetine weighted mean dosage 49.18 mg; 95% CI, 41.30 to 57.05), compared with trials conducted in Europe (fluoxetine weighted mean dosage 29.98 mg; 95% CI, 25.28 to 34.68). Since most clinical trials were conducted in Europe or the US, we could not determine whether different dosages tended to be used in other regions.


CONCLUSIONS
International differences in prescriber behaviour may influence, and in turn be influenced by, the conduct of clinical trials. It is difficult to reconcile such differences with the principles of evidence-based medicine.
Patten
Scott
S
Department of Community Health Sciences, University of Calgary, Alberta.
Cipriani
Andrea
A
Brambilla
Paolo
P
Nosè
Michela
M
Barbui
Corrado
C
D004334:Drug Administration Schedule; D011307:Drug Prescriptions; D005060:Europe; D005473:Fluoxetine / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019964:Mood Disorders / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D014481:United States
D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors