The Oral Dose-Effect Relationship for Fluvoxamine: a Fixed-Dose Comparison Against Placebo in Depressed Outpatients

Abstract

This 7- to 8-week, multicenter, randomized, double-blind, placebo-controlled study was performed to determine the dose-effect relationship and minimum effective dose for fluvoxamine maleate in a titrated fixed-dose study of major depressive disorder. Gradual titration over 2 weeks to fixed maintenance doses was employed to minimize dropout due to initial side effects. The study enrolled 600 outpatients, male and female, age 18-65, meeting DSM-III-R criteria for major depressive disorder. A 13-item subscore of the standard 21-Item Hamilton Depression Scale was used to minimize the possible contribution of known side effects from serotonin reuptake inhibitors to the overall HAM-D score. Secondary efficacy assessments included the HAM-D retardation factor, HAM-D depressed mood item, CGI-severity of illness item, and SCL depression factor. Fluvoxamine (50-150 mg/day) was therapeutically effective and well tolerated during 6 weeks of therapy. Based on the HAM-D depressed mood item, efficacy was dose dependent. The minimum effective dose was 50 mg/day. Fluvoxamine maleate shows dose-related effectiveness in the acute treatment of major depressive disorder.

Systematic Review and Meta-Analysis: Early Treatment Responses of Selective Serotonin Reuptake Inhibitors in Pediatric Major Depressive Disorder

“…35 A secondary parameter studied in our meta-analysis was the association of later publication year with smaller measured benefit of SSRI pharmacotherapy. On the other hand, recruitment start date was not associated with the measured benefit of SSRI pharmacotherapy.…”

Clinical use of the Hamilton Depression Rating Scale: is increased efficiency possible? A post hoc comparison of Hamilton Depression Rating Scale, Maier and Bech subscales, Clinical Global Impression, and Symptom Checklist-90 scores

“…Multidimensional scales can be misleading when measurement of severity and treatment response is concerned [13,21,28], especially when the measured depressive symptoms do not change proportionally with depression severity. Finally, some reports emphasize that the HDRS systematically favors (sedative) tricyclic antidepressants (TCAs) above selective serotonin reuptake inhibitors (SSRIs) [27,[32][33][34][35]. Sleep and somatic items may appear to be bimprovedQ by side effects of TCAs but worsened by side effects (eg, insomnia, gastrointestinal complaints, and agitation) of SSRIs.…”

Is there a SSRI dose response in treating major depression? The case for re-analysis of current data and for enhancing future study design

“…Additionally, the fixed-dose studies somewhat suggest an overall inverse relationship between dose and lack of response dropouts [Dunner and Dunbar, 1992;Fabre et al, 1995;Walczak et al, 1996;Wernicke et al, 1987Wernicke et al, , 1988 with 11.9% for lower dose, 13.5% for medium dose, and 8.4% for higher-dose groups. Given this relationship, if a completer sample is used for analysis, a potential dose-response relationship could be obscured.…”

“…The data in this figure are based upon all SSRI fixed-dose studies of major depression that report side-effect dropouts and lack of response dropouts for four dose levels including placebo [Dunner and Dunbar, 1992;Fabre et al, 1995;Walczak et al, 1996;Wernicke et al, 1988]. Side-effect dropouts increase from 7.8% to 12.2% to 16.3% to 24.1% across the dose levels.…”